Emergence Of New Psychoactive Substances Research Articles

Towards better prepared prisons: monitoring and response to the use of new substances inside prison

Abstract The use of new psychoactive substances (NPS) became an emerging issue in prisons in a number of European countries in 2014-2015. Synthetic cannabinoids were the new psychoactive substances most often reported, followed by synthetic cathinones, synthetic opioids and new benzodiazepines. Quantitative qualitative data on prison and drugs provided by 27 European Member States, Norway and Turkey to the EMCDDA (European Monitoring Centre for Drugs and Drug Addiction). An exploratory study conducted in 2017 found signs of NPS use in prison in 22 countries. Based on 2021-2022 data from a few countries, the lifetime prevalence of NPS in prison ranges from <1 to 19%, with large variation by country. Anecdotal information from 2024 referred to the use of new strong synthetic opioids (nitazene) inside prison. A wide range of physical and mental health harms (e.g. psychosis, disorientation, suicidal ideation, aggressiveness to others or self-harm) has been associated with acute intoxication by, and chronic consumption of NPS inside prison. Recent overdoses associated with the use of nitazene were reported in some prisons in Ireland and the UK. Additionally, the use of NPS in prison can have a disturbing impact on prison management, internal violence and bullying. To date, interventions to tackle the problems related to the use of NPS in prison have tended to focus on supply reduction and controls. Health and social interventions have begun to emerge, but they remain limited. Despite signs of increasing challenges posed by the emergence of NPS since several years, prisons remain largely unprepared to monitor and respond to those challenges. A new key task of the revised EMCDDA mandate (EUDA - European Drug Agency from 2nd of July) is to be better prepared to monitor, forecast and respond to new challenges in the drug field. Prisons should be prepared to adequately address the new challenges posed by the NPS to benefit the health and security of people living and working in prison.

High-performance liquid chromatography coupled to Orbitrap mass spectrometry for screening of common new psychoactive substances and other drugs in biological samples.

The complexity of the drug market and the constant updating of drugs have been challenging issues for drug regulatory authorities. With the emergence of new psychoactive substances (NPS) and the nonmedical use of prescription drugs, forensic and toxicology laboratories have had to adopt new drug screening methods and advanced instrumentation. Using high-performance liquid chromatography coupled with Orbitrap mass spectrometry, we developed a screening method for common NPS and other drugs. Two milliliters of mixed solvent of n-hexane and ethyl acetate (1:1, v:v) were added to 500 μL of blood or urine sample for liquid-liquid extraction, and methanol extraction was used for hair samples. The developed method was applied to 3897 samples (including 332 blood samples, 885 urine samples, and 2680 hair samples) taken from drug addicts in a province of China during 2019-2021. For urine and blood samples, the limits of detection (LODs) ranged from 1.68 pg/mL to 10.7 ng/mL. For hair samples, the LODs ranged from 3.30 × 10-5 to 4.21 × 10-3 ng/mg. The matrix effects of urine, blood, and hair samples were in the range of 47.6%-121%, 39.8%-139%, and 6.35%-118%, respectively. And the intra-day precision was 3.5%-6.0% and the inter-day precision was 4.18%-9.90%. Analysis of the actual samples showed an overall positive detection rate of 58.9%, with 5.32% of the samples indicating the use of multiple drugs.

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.

Wastewater analysis for new psychoactive substances and cocaine and cannabis in a Northern Ireland Prison

The global drug market has been significantly impacted by the emergence of new psychoactive substances, leading to challenges in creating effective legislative controls and their use within recreational drug consumption. This research explores the prevalence of new psychoactive substances and non-medicinal and medicinal compounds within a prison facility in Northern Ireland. Wastewater samples collected from seven different manholes within the prison were analysed for 37 target compounds including the two most found illicit substances: benzoylecgonine (primary metabolite of cocaine) and cannabis. Using solid phase extraction with Oasis HLB and liquid-chromatography-time-of-flight-mass spectrometry across a gradient of 9 min, our analysis revealed that benzoylecgonine was the sole compound consistently present in all collected samples. Following this finding, our target compound selection was broadened to encompass medicinal compounds and employing qualitative analysis we re-evaluated the samples and discovered the presence of buprenorphine, benzodiazepines, methadone, morphine, and codeine. Finally, the study explored the application of enzymatic beta-glucuronidase hydrolysis to the samples. This final phase yielded significant findings, indicating the presence of codeine and nordiazepam at higher peak intensities, thereby shedding light on the potential implications of this enzymatic process.

Comprehensive Toxicological Screening of Common Drugs of Abuse, New Psychoactive Substances, and Cannabinoids in Blood Using Supported Liquid Extraction and Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS).

Immunoassay (IA) is currently the most widely used technique for toxicological screening in drug impaired driving investigations. However, practical limitations in the scope of testing, and the emergence of new psychoactive substances (NPS), have highlighted the need for alternative approaches, particularly mass spectrometry-based screening. High resolution mass spectrometry (HRMS) broadens the scope of testing to include NPS, and increases analyte specificity compared to IA. In addition, it provides a platform with increased flexibility and adaptability to incorporate emerging drugs of interest due to the transient drug market. In this study, a comprehensive screening procedure was developed to identify more than two hundred drugs of interest, including cannabinoids and NPS in whole blood. Supported liquid extraction (SLE) and liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS) using All Ions data acquisition was employed. The method was validated in accordance with published recommendations, and all compounds of interest were identified at recommended cutoffs for driving under the influence of drugs (DUID) investigations. Cannabinoids, including 11-nor-9-carboxy-Δ9-THC (THC-COOH), fentanyl analogs, buprenorphine, novel synthetic opioids (NSOs), and synthetic cannabinoids were identified at low to sub-ng/mL concentrations in whole blood using both positive and negative electrospray ionization (ESI) acquisition methods.

Screening for new psychoactive substances in wastewater from educational institutions

Drug (ab)use among young people is a serious issue, negatively impacting their well-being and prospects. The emergence of new psychoactive substances (NPS) further complicates the situation as they are easily accessible (e.g., online), but users are at high risk of intoxication as their chemical identity is often unknown and toxicity poorly understood. While surveys and drug testing are traditionally used in educational institutions to comprehend drug use trends and establish effective prevention programs, they are not without their limitations. Accordingly, we investigated the occurrence of NPS in educational institutions through wastewater analysis and critically evaluated the viability of the approach. The study included eight wastewater samples from primary schools (ages 6–15 years), six from secondary schools (ages 15–19 years), three from institutions for both secondary and higher education (ages 15+), and six from higher educational institutions (ages 19+). Samples were obtained mid-week and evaluated in two Slovenian municipalities; the capital Ljubljana and a smaller one (M1). Samples were screened using liquid chromatography-ion mobility-high-resolution mass spectrometry (LC-IMS-HRMS), and NPS identified at three levels of confidence (Level 1: unequivocal, Level 2: probable, Level 3: tentative) from a suspect list containing over 5600 entries. NPS were identified in all types of educational institutions. Most were synthetic stimulants, with 3-MMC, ephedrine, 4-chloro-α-PPP, and ethcathinone being unequivocally identified. Also, NPS were present in wastewater from all educational institution types revealing potential spatial but no inter-institutional trends. Although specific groups cannot be targeted, the study, as a proof-of-concept, demonstrates that a suspect screening of wastewater employing LC-IMS-HRMS can be used as a radar for NPS in educational institutions and potentially replace invasive drug testing.

Prevalence of psilocybin use in vaping and associated factors: a study among amphetamine-type stimulants (ATS) use disorder in Malaysia

Background The emergence of New Psychoactive Substances (NPS), including synthetic psilocybin, has raised concern among health experts due to the numerous health and socioeconomic consequences. The current trend is shifting to the hazardous use of synthetic psilocybin in vaping, and little is known about the prevalence of use, specifically among amphetamine-type stimulants (ATS) users. Methods Interviewer-administered questionnaires were conducted in drug detention centers between March and October 2022. The study was conducted using ASSIST 3.0 and obtained information on the respondents’ socio-demographic characteristics and clinical profiles. N = 355 ATS users were enrolled in this study. Results The results show a high prevalence of psilocybin vaping among ATS users (182/355, 53.1%). Most of the respondents were males (85.1%) and unmarried (69.3%), with a mean age of 29.2 (SD = 7.3). Across all respondents, five factors were associated with psilocybin vaping: tobacco smoking, aOR =5.790 (95% CI: 1.723, 8.183); cannabis uses, aOR= 9.152 (95% CI: 2.693, 10.396); and alcohol use, aOR= 3.137 (95% CI: 1.461, 5.817). Respondents of the Malay race had higher odds of being involved in psilocybin vaping compared to other races, with aOR= 1.638 (0.043, 2.459). Meanwhile, a reduction in age by 1.9 will increase the likelihood of involvement in psilocybin vaping with aOR = 1.897 (95% CI: 0.857, 1.938). Conclusion Psilocybin in vaping is growing among ATS users and across all populations. Unfortunately, knowledge regarding the long-term effects on health is limited. Further studies should highlight the harmful effects of psilocybin and the potential risk of psilocybin vaping among the younger population.

Rapid and sensitive dilute-and-shoot analysis using LC-MS-MS for identification of multi-class psychoactive substances in human urine

The emergence of new psychoactive substances currently exceeding a thousand is rapidly changing substance prevalence patterns and straining the methods used for detection, most of which are suitable only for a single class of substances. This study presents a rapid and facile dilute-and-shoot system operated in conjunction with an optimized liquid chromatographic separation system for the high-sensitivity detection of substances across a range of substance classes with 3 isotopes used only. The proposed method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) is able to identify 68 substance and their metabolites in urine samples as small as 50 μL. Optimal chromatographic conditions including 95% water/methanol ratio with 0.1% added formic acid and a prolonged LC gradient run-time (15 min) improved the peak shape of polar compounds and enhanced signal strength by 5%. Under 4-fold dilution, all analytes were within 80–120% of tolerance response levels, indicating that the matrix effect was insignificant. In experiments, the limit of detection (LOD) ranged from 0.05 to 0.5 ng mL−1, while the coefficient of determination (R2) was > 0.9950. The retention time shift of each peak remained at < 2% with an inter-day relative standard deviation (RSD) of 0.9–14.9% and intra-day RSD of 1.1%− 13.8%. The rapid dilute-and-shoot presents a high-sensitivity, significant stability, robustness and reproducibility without serious interference. To demonstrate the effectiveness of the system, 532 urine samples were collected from suspected drug abusers, and the proposed method was used for rapid analysis. Of these samples, 79.5% contained between one and twelve analytes, and 12.4% tested positive for new psychoactive substances, mostly derivatives of amphetamine and synthetic cathinones. The study presents a high-sensitivity analytic system that is capable of detecting substances from multiple classes and can be used for effective monitoring of substance prevalence in urine.

Epidemiological patterns of new psychoactive substances use in Tunisian school adolescents, 2021

IntroductionThe emergence of New Psycho-active Substances (NPS) such as Synthetic cannabinoid and cathinone, represents a challenging issue for drug policy globally. In order to set up new adjusted measures to limit this phenomenon extension, objective epidemiologic indicators are requested.ObjectivesWe aimed to determine the prevalence of Synthetic cannabinoid and cathinone consumption in Tunisian adolescents by gender and regional distribution.MethodsData from the Mediterranean school survey on alcohol and other drugs (MedSPAD III-2021) were used. Based on three-stage stratification sampling method, high school teenagers in first and second grades of secondary education, were enrolled. Data collection was performed using a self-administered standardized questionnaire. We examined weighted prevalence estimates of NPS use at least once in a lifetime (Synthetic cannabinoid and cathinone) by gender and regional distribution. Epi data software was used for data entry and all statistical analysis were performed with STATA software.ResultsThe survey included 6201 adolescents with a mean age of 16.8 years and a sex ratio female/male of 1.5. Synthetic cannabinoid’s use was reported by 1.9%, 95% CI [1.57-2.39] of students, with statistically significant difference between boys (4.1%) and girls (0.6%), p-value&lt;10-4 . This consumption was the highest in Tunis the capital city, the center-east and the north-east (2.7%, 2.2% and 2% respectively). As for synthetic cathinone’s use, it was reported by 0.36% 95%CI [0.24-0.56] of our study sample, with statistically significant difference between boys (0.8%) and girls (0.8%), p-value&lt;10-4 .ConclusionsOur study highlighted an emerging use of NPS among high school students with significant male predominance. Further research on NPS epidemiology is, hence, needed to reinforce evidence-based management strategies aiming at fighting this phenomenon. Sensitization of decision makers to control accessibility, and increasing awareness among adolescents’ close family / school-staff environment regarding this issue, are strongly recommended.Disclosure of InterestNone Declared

Neuropsychiatric effects of Synthetic Cathinones - a review

IntroductionThe emergence of new psychoactive substances (NPS) has had a substantial impact worldwide. NPS mimic the effect of “existing” drugs and are specifically manufactured so that the new substances fall out of regulatory frameworks. Although the structural changes might be minimal, NPS often have marked differences in potency and subsequent harm.The population of the Azores archipelago has been particularly affected by the rapid growing and changing nature of this phenomenon, mainly caused by the introduction and spread of the “newly” synthetic cathinones as a inexpensive and easily available street drug.Before any educational, public health and socioeconomic policy changes be proposed to accurately tackle the problem, the basic step of knowing how these substances have been affecting their users, specially their neuropsychiatric effects, must be taken.ObjectivesThis project aims to characterize the neuropsychiatric side effects caused by the acute intoxication of NPS with a psychostimulant profile, namely synthetic cathinones.MethodsDescription of the neuropsychiatric symptoms of intoxicated users of stimulant NPS that present to non-governmental organizations specialized in addictions and also to the psychiatry emergency department in Sao Miguel - Azores.Review of the forensic records of the deaths by suicide in 2021 in Sao Miguel, looking for evidence of recent abuse of NPS or previous history of “NPS use disorder”.Non-systematic review of the recent and relevant scientific literature on this topic.ResultsThe desired effects are increased energy, mood enhancement, euphoria, mental clarity, improved concentration, improved sociability, increased talkativeness, empathy inducing effects, amplification of sound and colour and prosexual effects. Nevertheless, in the case of intoxication, the frequent neuropsychiatric side effects tend to be agitation, agressiveness, irritability, altered consciousness, brief psychosis with paranoid delusion, visual and auditive hallucinations, transient mania, enhanced sensorial experiences, headaches, dizzyness, seizures, confusion and amnesia. Usually, the acjute intoxication period tend to be followed by a “crash” with depression, craving, anxiety, panic, suicidal ideation and behaviours. A third of the deaths by suicides in Sao Miguel Island in 2021, 7 out of 21, were in stimulant NPS active or recent users.ConclusionsReview of the neuropsychiatric effects of New Psychoactive Substances with a psychostimulant profile. Further studies of this population of synthetic cathinone users in the Azores are due, namely studying their socioeconomic background, looking for risk and protective factors, and also the long-term side effects.Disclosure of InterestNone Declared

Stability studies of ALD-52 and its homologue 1P-LSD.

With the emergence of new psychoactive substances (NPSs) over the years, the substances detected on stamps (also known as blotter papers) have also evolved from the traditional drug-lysergic acid diethylamide (LSD) to the multiple variants of lysergamides such as ALD-52 and 1P-LSD. The analysis of such blotter papers is usually done by solvent extraction followed by identification using gas chromatography-mass spectrometry (GC-MS). This study has shown that hydrolysis to form LSD was observed in GC-MS analysis when ALD-52 was extracted with methanol. The extraction of ALD-52 using other solvents such as acetonitrile, ethanol, isopropyl alcohol, ethyl acetate, and acetone, followed by GC-MS analysis, was investigated. It is shown that alcoholic solvents such as methanol and ethanol will result in the conversion of ALD-52 to LSD during GC-MS analysis, whereas the sterically hindered isopropyl alcohol will prevent this conversion. Investigation also shows that the hydrolysis of ALD-52 to LSD occurs at the GC injector port. It was also observed that the degree of hydrolysis was more pronounced at a lower concentration (0.1mg/mL). The study was extended to a close analog-1P-LSD, and the results showed that 1P-LSD similarly hydrolyzes to LSD. However, 1P-LSD was observed to be more stable than ALD-52 due to steric hindrance because of the propanoyl group.

Rapid Detection of Synthetic Cannabinoid Receptor Agonists Impregnated into Paper by Raman Spectroscopy

Abstract English The last decade has witnessed the emergence of new psychoactive substances that are analogues of classical drugs of abuse in order to escape the regulations surrounding the latter drugs. These drugs were of both herbal and synthetic origin and were advertised initially as ‘legal highs’; thus, they were perceived as safe by users. Hence, upon their emergence, they were not controlled by the Misuse of Drugs Act 1971, which contributed to their popularity and increased sales online and within street markets. In 2016, the Psychoactive Substance Act introduced a blanket ban on all new psychoactive substances except for caffeine, alcohol, and nicotine. This in turn, contributed to the change in the sale of new psychoactive substances products that have been sold as concealed in different matrices, including herbal products, papers, fabrics, and textiles. Concealing drugs in paper has been very popular, especially since the drug product is of lightweight and can be sent via postal services. However, new psychoactive concealed in papers are toxic not only to the users; but also, to the person handling them (i.e. mail employees). One of the classes of new psychoactive substances that have been commonly concealed in papers and that have been linked to toxicity and hospitalization cases is synthetic cannabinoids. Therefore, there is a need to identify new psychoactive substances concealed in papers non-destructively and rapidly to prevent toxicity linked to them. Handheld Raman spectroscopy offers this advantage as it is of lightweight and carries the sample to the matrix. Therefore, this work used handheld Raman spectroscopy for identifying synthetic cannabinoids concealed in papers using Raman spectroscopy combined with machine learning analytics. Synthetic cannabinoid and paper samples were measured non-destructively using a handheld Raman spectrometer equipped with a 1064 nm laser wavelength. Spectral data was exported into Matlab 2020b where machine learning analytics including identification and prediction was. The results showed that Raman spectroscopy could identify specific synthetic cannabinoids in papers that were either deposited on the surface of the paper or diffused inside the paper substrate. When machine learning analytics were applied to the Raman spectra of the papers, quantitative information was obtained regarding the amount of synthetic cannabinoid deposited on the paper surface. In summary, handheld Raman spectroscopy could identify and quantify synthetic cannabinoids on paper rapidly and non-destructively. Future work involves testing other classes of new psychoactive substance and applying deep learning analytics

One-step extraction and determination of 513 psychoactive substances, drugs, and their metabolites from hair by LC–MS/MS

The emergence of new psychoactive substances on the market is a significant problem on a global scale. This type of substance in society is associated with many negative consequences, such as traffic accidents, accidents at work, rape, homicide, poisoning, or overdose deaths. The analysis of these substances in biological samples is very important for further legal action and saving lives. Therefore, laboratories face a tremendous challenge in tackling the evolving drug market. The paper describes the optimization of the analytical LC–MS/MS method to identify and determine 513 psychoactive substances in hair samples. A method of chromatographic separation was developed, and the working parameters of the mass spectrometer were selected for each analyte. The method has been validated, and the results are as follows: the limit of quantification of the developed method ranges from 0.025 to 1.25 ng/mg hair. The mean recovery of the tested analytes ranges from 80 to 120%. The achieved coefficient of variation in within-run precision ranged from 1.05 to 19.99%. The results achieved for BIAS are in the range of ± 20%.

Newly emerging synthetic cannabinoids and novel modes of use of benzodiazepines in prisons: An update from the Scottish Prisons Non-Judicial Seizures Drug Monitoring Project

In July 2021, the Chinese government implemented analogue controls for synthetic cannabinoid receptor agonists (SCRAs) covering the most popular compounds on the market at the time. International legislation is one of the main driving forces of market change and prisons can act as an early warning system for the emergence of new psychoactive substances (NPS) and novel modes of use. This study reports the latest synthetic cannabinoid receptor agonists (SCRAs) and benzodiazepines to emerge in the Scottish prisons following the international controls and the new modes of use of benzodiazepines that have emerged. Since the start of the Scottish Prisons Non-Judicial Seizures Drug Monitoring Project in September 2018, over 1600 individual samples from over 1200 unattributable suspected drug seizures have been tested. Samples included infused paper and card, tablets, powders, infused clothing, and blotters. Qualitative screening of seized samples suspected to contain controlled substances was carried out using gas chromatography-mass spectrometry (GC-MS) with verification by comparison to reference standards and/or orthogonal analysis by ultra-performance liquid chromatography with quadrupole time of flight mass spectrometry (UPLC-QToF-MS) if reference standards were not available. Following the enactment of the Chinese analogue controls for SCRAs in July 2021, seven new (or re-emerged) compounds have been detected in the Scottish prisons that circumvent this legislation, including 5F-3,5-AB-PFUPPYCA and 5,3-ADB-4en-PFUPPYCA in Q3 2021; BZO-HEXOXIZID (MDA-19), MDMB-5Br-INACA, ADB-5Br-INACA, and ADB-FUBIATA in Q4 2021; and CH-PIATA in Q1 2022. However, despite being controlled by this Chinese legislation, ADB-BUTINACA has remained the most common SCRA detected within the Scottish Prisons, appearing in over 66% of all SCRA samples since its first detection in Q1 2021. This could be due to a supply stockpile; production in other countries, such as India; or a new “self-assembly” product where people buy a pre-synthesis product, such as ADB-5Br-INACA, in a set with additional chemicals and instructions to complete the synthesis themselves. Etizolam was the most commonly detected benzodiazepine, appearing in over 81% of all benzodiazepine samples since Q1 2021, despite its international control in March 2020. Once again, this could be due to a supply stockpile or production in other countries without an etizolam control, such as India. Although there may be other routes of supply for etizolam, other benzodiazepines have emerged that are not internationally controlled, including flubromazepam and bromazolam. Flubromazepam emerged in Q3 2021 and since then has been detected in over 35% of benzodiazepine samples. In Q4 2020, benzodiazepines began to be detected in infused card and paper, a method previously almost exclusively used with SCRAs. By Q3 2021, card and paper became the most common matrix for benzodiazepines in the Scottish prisons. Benzodiazepine-infused cards and papers are often boiled in kettles and the liquid ingested; however, they are also vaped. There is little, if any, published information to date regarding the effects or harms of smoking or vaping benzodiazepines. Near-real time analysis of seized samples is vital for the rapid detection of new NPS compounds emerging in prisons and the general population in response to changes in international legislation. Compounds may have different potency and/or effects depending on the mode of use, so it is important for intelligence around modes of use to be gathered and investigated.

Serotonin syndrome onset following 25H-NBOH and MDPHP consumption: A case report

The continual emergence of new psychoactive substances remains a global health issue. We reported a case of serotoninergic syndrome following the consumption of 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) and 25H-NBOH documented by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). A 23-year-old man, with a history of cathinone regular use, presented a seizure and a loss of consciousness 30 min after the consumption of a powder identified as 25I-NBOH. The way of exposure was not documented. On arrival at the mobile emergency unit, the patient exhibited a serotonin syndrome with hyperthermia at 41 °C, hypertonia of the upper limbs, bilateral mydriasis, Glasgow coma 3, hypertension at 16/8, tachycardia at 180 bpm, and SaO 2 = 50%. During the hospitalization, he developped acute renal failure, acute liver failure, rhabdomyolysis and disseminated intravascular coagulation. He was discharged after 20 days of hospitalization but kept neurological sequelae. Following his hospital admission, blood and urine samples were drawn and sent to the toxicology laboratory to determine the cause of poisoning. In total, 200 μL of plasma and urine samples were extracted with QuEChERS salts and acetonitrile. The extracts were analyzed by liquid chromatography hyphenated to high-resolution mass spectrometry (Orbitrap, Exploris 120) allowing both a non-targeted screening and the simultaneous quantification of 132 compounds frequently found in poisonings. Analysis was realized in full scan experiment with a nominal resolving power of 60,000 FWHM within the 125–650 m/z mass range, followed by four cycles of DDA with a mass resolution of 16,000 FWHM. Pharmaceuticals administered to the patient during his medical care were found in plasma and urine: midazolam, hydroxyzine and its metabolite cetirizine, ketamine, etomidate, laudanosine (atracurium metabolite), lidocaine. Additionally, two NPS were identified and then confirmed with certified reference materials (CRM): MDPHP in plasma and urine, and 25H-NBOH in urine. 25H-NBOH was not detected in plasma despite a limit of detection being 0.01 ng/mL. Unfortunately, there were not enough remaining samples after the screening analyzes, therefore the quantification could not be carried out. In order to estimate the concentration, a calibration curve was carried out with the two compounds under the same conditions as the screening analysis (same pretreatment, same internal standards at the same concentrations, as well as the same analytical conditions), and the data corresponding to the initial acquisition was then reprocessed. MDPHP concentration was 1 ng/mL in plasma and 48 ng/mL in urine, 25H-NBOH concentration was 0.4 ng/mL in urine. 25I-NBOH was specifically searched in both samples and was not detected. MDPHP is a synthetic cathinone of the pyrovalerone type (e.g. MDPV), it acts as a stimulant on the release of dopamine and norephedrine and simultaneously as reuptake inhibitor, causing a pronounced stimulatory effect on the central nervous system (Grapp M, et al., Drug Test Anal 2020;12:1320–35). 25H-NBOH is a psychedelic belonging to the NBOMe family, they are potent agonists of 5-HT2A receptor (Pottie et al., Biochem Pharmacol 2020;182:114251). The clinical manifestations observed here are similar to those described in cases of NBOMe poisoning, and are probably attributable to 25H-NBOH, they may have been potentiated by the presence of MDPHP (Kyriakou C, et al., Eur Rev Med Pharmacol Sci 2015;19:3270–81). To our knowledge, very few study have been dedicated to MDPHP poisoning, and this is the first describing 25H-NBOH poisoning.

Application of Metabonomics in Substance Abuse Toxicology Research.

Abstrct: Metabonomics is a relative discipline that develops after genomics and proteomics, and it is an important component of systems biology. It uses high-throughput and high-sensitivity instruments to perform qualitative and quantitative analysis of all metabolic components in specific biological samples under limited conditions and combines with multivariate statistics to analyze and process the data to obtain information about physiological, pathological or toxicological changes in organisms. In recent years, because of the complicated mechanism of substance abuse and the continuous emergence of new psychoactive substances, metabonomics is increasingly used in substance abuse research. Therefore, this article reviews the application of metabonomics of substance abuse in the toxic mechanism, the mechanism of addiction and the discovery of biomarkers.

Pharmacological affinity fingerprints derived from bioactivity data for the identification of designer drugs

Facing the continuous emergence of new psychoactive substances (NPS) and their threat to public health, more effective methods for NPS prediction and identification are critical. In this study, the pharmacological affinity fingerprints (Ph-fp) of NPS compounds were predicted by Random Forest classification models using bioactivity data from the ChEMBL database. The binary Ph-fp is the vector consisting of a compound’s activity against a list of molecular targets reported to be responsible for the pharmacological effects of NPS. Their performance in similarity searching and unsupervised clustering was assessed and compared to 2D structure fingerprints Morgan and MACCS (1024-bits ECFP4 and 166-bits SMARTS-based MACCS implementation of RDKit). The performance in retrieving compounds according to their pharmacological categorizations is influenced by the predicted active assay counts in Ph-fp and the choice of similarity metric. Overall, the comparative unsupervised clustering analysis suggests the use of a classification model with Morgan fingerprints as input for the construction of Ph-fp. This combination gives satisfactory clustering performance based on external and internal clustering validation indices.

Controlling new psychoactive substances in New Zealand

ABSTRACT The emergence of new psychoactive substances into the global drug market has presented challenges for effective drug legislation and enforcement. One approach to prohibition uses controlled drug analogue legislation, which involves assessing the structural similarity of new substances compared to listed controlled drugs, as opposed to the new substance being specifically listed in legislation itself. An issue arises of there being no clear definition for what constitutes similarity between two substances, and as such, there is level of subjectivity in any decision made. This paper outlines the global and local drug scene in New Zealand, including the emergence of new psychoactive substances, and the legislation that is available for the control of illicit substances in a New Zealand context and the current method for considering new psychoactive substances as potential controlled drug analogues. The authors go on to propose an alternative method to this assessment process, which involves an objective and reproducible similarity scoring mechanism.

Jump-starting the conversation about harm reduction: making sense of drug effects

This paper describes the history of the development of taxonomies of psychoactive drug use, and discusses the conceptualization of three recent taxonomies: comparing their features, and considering their application in education, treatment, and harm reduction settings. Firstly, the Drugs Wheel was created in 2012, prompted by the emergence of New Psychoactive Substances and rapid developments in their legislative control. It was created in collaboration with health professionals and trainers in the drugs field, people who use drugs, and harm reduction non-government organizations, as a learning tool for NPS. Secondly, by contrast, the Drug Pyramid was an academic creation published in 2016 that aimed to conceptualize the multitude of NPS then being developed at a rate of two per week, as primarily an educational project. Finally, building from limitations identified in the previous two models, the Drugs Venn was created by the authors for the purpose of this paper and in consultation with staff at a drug checking service provider, with the intention of future application in delivery of drug checking consultations. Viewed together, each model addresses objections raised to its predecessor, and in doing so highlights the multi-dimensional nature of taxonomies, and their potential for generation of further hypotheses.

An Update on the Implications of New Psychoactive Substances in Public Health.

The emergence of new psychoactive substances has earned a great deal of attention, and several reports of acute poisoning and deaths have been issued involving, for instance, synthetic opiates. In recent years, there have been profound alterations in the legislation concerning consumption, marketing, and synthesis of these compounds; rapid alert systems have also been subject to changes, and new substances and new markets, mainly through the internet, have appeared. Their effects and how they originate in consumers are still mostly unknown, primarily in what concerns chronic toxicity. This review intends to provide a detailed description of these substances from the point of view of consumption, toxicokinetics, and health consequences, including case reports on intoxications in order to help researchers and public health agents working daily in this area.