Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan

New Psychoactive Substances (NPS) are a global concern since they are spreading at an unprecedented rate. Despite their commerce still being limited compared to traditional illicit drugs, the identification of NPS in seizures may represent a challenge because of the variety of possible structures. In this study we report the successful application of molecular networking (MN) to identify unexpected fentanyl analogs in two seizures. The samples were extracted with 1 mL of methanol and analyzed with an untargeted data-dependent acquisition approach by LC–HRMS. The obtained data were examined using the MN workflow within the Global Natural Product Search (GNPS). A job was submitted to GNPS by including both seizures and standard mixtures containing synthetic cannabinoids and fentanyls raw files; spectra obtained from standards were used to establish representative networks for both molecular classes. All synthetic cannabinoids in the mixture were linked together resulting in a molecular network despite their different fragmentation spectra. Looking at fentanyls, all the molecules with the typical 188.143 and 105.070 fragments were combined in a representative network. By exploiting the standard networks two unexpected fentanyls were found in the analyzed seizures and were putatively annotated as para-fluorofuranylfentanyl and (iso)butyrylfentanyl. The identity of these two fentanyl analogs was confirmed by NMR analysis. Other m/z ratios in the seizures were compatible with fentanyl derivatives; however, they appeared to be minor constituents, probably impurities or synthetic byproducts. The latter might be of interest for investigations of common fingerprints among different seizures.

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Screening of 104 New Psychoactive Substances (NPS) and Other Drugs of Abuse in Oral Fluid by LC–MS-MS

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa089 ◽

2020 ◽

Vol 44 (7) ◽

pp. 697-707

Author(s):

Kelly Francisco da Cunha ◽

Karina Diniz Oliveira ◽

Marilyn A Huestis ◽

Jose Luiz Costa

Keyword(s):

Oral Fluid ◽

Drugs Of Abuse ◽

Matrix Effects ◽

Synthetic Cannabinoids ◽

Screening Method ◽

Simultaneous Detection ◽

New Psychoactive Substances ◽

Major Public Health Problem ◽

Psychoactive Substances ◽

Wide Range

Abstract New psychoactive substances (NPS) are a major public health problem, primarily due to the increased number of acute poisoning cases. Detection of these substances is a challenge. The aim of this research was to develop and validate a sensitive screening method for 104 drugs of abuse, including synthetic cannabinoids, synthetic cathinones, fentanyl analogues, phenethylamines and other abused psychoactive compounds (i.e., THC, MDMA, LSD and their metabolites) in oral fluid by liquid chromatography–tandem mass spectrometry (LC–MS-MS). The Quantisal™ oral fluid device was used to collect oral fluid samples. The oral fluid–elution buffer mixture (500-μL sample) was extracted with t-butyl methyl ether, and chromatographic separation was performed on a Raptor™ biphenyl column (100 × 2.1 mm ID, 2.7 μm), with a total run time of 13.5 min. Limits of detection were established at three concentrations (0.05, 0.1 or 1 ng/mL) for most analytes, except for acetyl norfentanyl and mescaline (5 ng/mL). Matrix effects were generally <20% and overall extraction recoveries >60%. The highest matrix effect was observed within the synthetic cannabinoid group (PB22, −55.5%). Lower recoveries were observed for 2C-T (47.2%) and JWH-175 (58.7%). Recoveries from the Quantisal™ device were also evaluated for all analytes (56.7–127%), with lower recoveries noted for 25I-NBOMe, valerylfentanyl and mCPP (56.7, 63.0 and 69.9%, respectively). Drug stability in oral fluid was evaluated at 15, 60 and 90 days and at 25, 4 and −20°C. As expected, greater stability was observed when samples were stored at −20°C, but even when frozen, some NPS (e.g., synthetic cannabinoids) showed more than 20% degradation. The method was successfully applied to the analysis of seven authentic oral fluid samples positive for 17 different analytes. The method achieved good sensitivity and simultaneous detection of a wide range of NPS.

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Recent bionalytical methods for the determination of new psychoactive substances in biological specimens

Bioanalysis ◽

10.4155/bio-2020-0148 ◽

2020 ◽

Vol 12 (21) ◽

pp. 1557-1595

Author(s):

Ana Y Simão ◽

Mónica Antunes ◽

Hernâni Marques ◽

Tiago Rosado ◽

Sofia Soares ◽

...

Keyword(s):

Acute Toxicity ◽

Analytical Methods ◽

Synthetic Cannabinoids ◽

New Psychoactive Substances ◽

Screening Methods ◽

Psychoactive Substances ◽

Clinical Action ◽

One Step ◽

Preparation Techniques

One of the problems associated with the consumption of new psychoactive substances is that in most scenarios of acute toxicity the possibility of quick clinical action may be impaired because many screening methods are not responsive to them, and laboratories are not able to keep pace with the appearance of new substances. For these reasons, developing and validating new analytical methods is mandatory in order to efficiently face those problems, allowing laboratories to be one step ahead. The goal of this work is to perform a critical review regarding bionalytical methods that can be used for the determination of new psychoactive substances (phenylethylamines, cathinones, synthetic cannabinoids, opioids, benzodiazepines, etc), particularly concerning sample preparation techniques and associated analytical methods.

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Streets of the ‘spice zombies’: Dependence and poverty stigma in times of austerity

Crime Media Culture An International Journal ◽

10.1177/1741659019835274 ◽

2019 ◽

Vol 16 (1) ◽

pp. 97-113 ◽

Cited By ~ 8

Author(s):

Liviu Alexandrescu

Keyword(s):

Synthetic Cannabinoids ◽

Public Spaces ◽

Cultural Analysis ◽

New Psychoactive Substances ◽

The Political ◽

Psychoactive Substances ◽

Political Discourses ◽

The United Kingdom ◽

The Poor ◽

National Media

Following the 2016 general ban on new psychoactive substances, synthetic cannabinoids (‘spice’-type drugs) have moved into unregulated street markets and have become popular among homeless populations in the United Kingdom. Images of so-called ‘spice zombies’, rough sleepers in public spaces experiencing severe substance-induced fits, have been used by local and national media to suggest the growing scale of the problem. This article proposes that such depictions should be read through a cultural analysis rooted in the political economy of austerity policies, where the twofold stigma of substance and welfare dependencies directs guilt at the poor, concealing the systemic cruelty of benefits reforms. Through the circulation of such tropes and the ridiculing of a superfluous abject underclass that embodies them, media and political discourses of the ‘broken society’ highlight an evident need for welfare reduction and more generally for the austerity project.

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MT-45: A new, dangerous legal high

Journal of Opioid Management ◽

10.5055/jom.2014.0219 ◽

2014 ◽

Vol 10 (5) ◽

pp. 301 ◽

Cited By ~ 5

Author(s):

Maurizio Coppola, MD ◽

Raffaella Mondola, MD

Keyword(s):

Prescription Drugs ◽

Synthetic Cannabinoids ◽

Epidemiological Data ◽

New Psychoactive Substances ◽

Psychoactive Substances ◽

Legal Highs ◽

Smart Drugs ◽

Research Chemicals ◽

Medical Emergencies ◽

Legal High

Epidemiological data confirm that the use of new psychoactive substances is on the rise around the world.1 Numerous reports have described medical emergencies associated with the consumption of unconventional drugs of misuse bought in “head” or “smart” shops or online.1 New psychoactive substances, also referred as “legal highs,” “smart drugs,” or “research chemicals,” are a large group of both plant derivatives and synthetic compounds, also in combination, purposefully designed as legal alternatives to illicit substances of abuse. The most popular and widely-spread new psychoactive substances are synthetic cannabinoids and synthetic cathinones, however, various different compounds such as amphetamine-like molecules, arylcyclohexylamines, synthetic hallucinogens, prescription drugs and hormones have been found in recreational products marketed as legal highs.1

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New psychoactive substances: psychiatrist's view

Interactive science ◽

10.21661/r-497066 ◽

2019 ◽

pp. 57-67

Author(s):

Andrey Viktorovich Antsyborov ◽

Irina Vladimirovna Dubatova

Keyword(s):

Opioid Receptors ◽

Psychotic Disorders ◽

Synthetic Cannabinoids ◽

Designer Drugs ◽

New Psychoactive Substances ◽

Psychoactive Substances ◽

Gaba A ◽

Psychoactive Effects ◽

Legal High ◽

Derivatives Of

Appearing not long ago, new psychoactive substances (designer drugs), including synthetic cannabinoids, derivatives of cathinone, phenethylamines, new stimulants, synthetic opioids, tryptamine derivatives, phencyclidine, piperazine, the GABA (A/B) receptors agonists, have become a serious problem for consumers and for physicians. Consumers of these substances are attracted primarily by the intensity of psychoactive effects, and the «legal high» declared by the black manufacturers, which indicates that significant difficulties in a laboratory identification of new surfactants. Designer drugs, when ingested, can be influenced on many neurotransmitter pathways/receptors: dopamine, cannabinoid (CB1), GABA (A/B), 5-HT2A, glutamate, and k-opioid receptors (KOR), the imbalance of which leads to the development of polymorphic psychotic disorders.

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Sex and Gender Differences in the Effects of Novel Psychoactive Substances

Brain Sciences ◽

10.3390/brainsci10090606 ◽

2020 ◽

Vol 10 (9) ◽

pp. 606

Author(s):

Liana Fattore ◽

Matteo Marti ◽

Rafaela Mostallino ◽

Maria Paola Castelli

Keyword(s):

Gender Differences ◽

Illicit Drugs ◽

Drugs Of Abuse ◽

Subjective Effects ◽

Synthetic Cannabinoids ◽

New Psychoactive Substances ◽

Sex And Gender ◽

Psychoactive Substances ◽

And Gender ◽

Sex And Gender Differences

Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of “classic” drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood.

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The synthetic cannabinoids: JWH, four years of analysis

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.123 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S115-S116 ◽

Cited By ~ 1

Author(s):

L. Galindo ◽

M. Grifell ◽

P. Quintana ◽

A. Palma ◽

J. Tirado ◽

...

Keyword(s):

Cannabinoid Receptors ◽

Scientific Evidence ◽

Synthetic Cannabinoids ◽

Gas Chromatography Mass Spectrometry ◽

New Psychoactive Substances ◽

Psychoactive Substances ◽

Legal Highs ◽

Energy Control ◽

Competing Interest ◽

Herbal Mixtures

IntroductionSince 2004, herbal mixtures for smoking use have been sold under the generic brand “Spice”. Many of them contain synthetic cannabinoids (agonists of the cannabinoid receptors). JWH-018 was one of the first spice drugs. There is no scientific evidence of their effects on humans, except cases of intoxications and users opinions.ObjectiveThe present study describes the presence of the synthetic cannabinoids JWH's and their characteristics in the samples delivered for analysis to the harm reduction NGO Energy Control from 2010 to 2014 in Spain.MethodsFrom 15,814 samples analyzed from 2010 to 2014, those containing synthetic cannabinoids JWH's were studied (n = 47). Analysis was done by gas chromatography–mass spectrometry.ResultsFrom these 47 samples containing JWH, 55% were delivered as “legal highs” (n = 21) and 44% as JWH. Most common presentations were powder 47% and herbals 32%. Samples containing JWH 45%(n = 21) were mixed with more than one kind of JWH or were adulterated and other active principles were found 28% (n = 13) JWH-018, 11% (n = 5) JWH-210, 8% (n = 4) JWH-081 and the 6% WH-250 (n = 3). Origin of the sample was Catalunya 23% (n = 11), other provinces of Spain 46% (n = 22); other EU countries 23% (n = 11) and internet-unknown country 8% (n = 8). From the (n = 47) samples, were delivered (n = 16) in 2012, (n = 12) in 2013, (n = 11) in 2011, (n = 3) in 2010 and (n = 3) in 2014.ConclusionJWH'S represent a low percentage of new psychoactive substances analyzed. Its presence in the market seems decreasing.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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New Psychoactive Substances and Suicidality: A Systematic Review of the Current Literature

Medicina ◽

10.3390/medicina57060580 ◽

2021 ◽

Vol 57 (6) ◽

pp. 580

Author(s):

Stefania Chiappini ◽

Alessio Mosca ◽

Andrea Miuli ◽

Maria Chiara Santovito ◽

Laura Orsolini ◽

...

Keyword(s):

Mental Health ◽

Synthetic Cannabinoids ◽

Cochrane Library ◽

New Psychoactive Substances ◽

Psychoactive Substances ◽

Clinical Issue ◽

The Past ◽

Synthetic Opioids ◽

Online Databases ◽

Health Related

Background and Objectives: Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated with health-related risks, especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self-injurious behavior. This paper aims at providing an overview of NPS abuse and the effects on mental health and suicidality issues, by performing a literature review of the current related knowledge, thereby identifying those substances that, more than others, are linked to suicidal behaviors. Materials and Methods: A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been undertaken. An electronic search was performed, including all papers published up to March 2021, using the following keywords “NPS” OR “new psychoactive substances” OR “novel psychoactive substances” OR “synthetic cannabinoids” OR “phenethylamines” OR “synthetic cathinones” OR “tryptamines” OR “piperazines” OR “new synthetic opioids” OR “designer benzodiazepines” AND (“suicide” OR “suicidality”) NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. Results: Suicidality and self-injurious behavior appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. The results are organized according to the substances recorded. Conclusion: The growing use of NPS has become a significant clinical issue, causing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviors, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring, and restriction of NPS.

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Unexpected results found in larvae samples from two postmortem forensic cases

Forensic Toxicology ◽

10.1007/s11419-021-00601-x ◽

2021 ◽

Author(s):

Olwen Groth ◽

Simon Franz ◽

Helena Fels ◽

Julia Krueger ◽

Gabriele Roider ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Illicit Drugs ◽

Synthetic Cannabinoids ◽

Stomach Contents ◽

Pericardial Fluid ◽

Supplementary Information ◽

New Psychoactive Substances ◽

Psychoactive Substances ◽

Toxicological Analysis

Abstract Purpose In forensics, entomological specimens can be used as additional/alternative matrices to detect xenobiotics when human specimens are limited in their application. Despite some advantages over implementing putrefied human remains, most medico-legal laboratories do not include entomotoxicological procedures as routine analytical methods. We thus applied two authentic cases to evaluate necrophagous larvae’s potential as complementary matrices for toxicological analysis after extensive postmortem decomposition. Methods Larvae and postmortem human samples, including hair, stomach contents, pericardial fluid, liver, lung, and skeletal muscle, were collected at autopsy. Samples were analyzed by liquid chromatography–tandem mass spectrometry and liquid chromatography–quadrupole time-of-flight mass spectrometry for pharmaceutical substances, illicit drugs, and new psychoactive substances, including synthetic cannabinoids, benzodiazepines, new synthetic opioids, and stimulants. Results Nearly all substances detected in human specimens, including several benzodiazepines and synthetic cannabinoids, were also detected in larvae. Surprisingly, some drugs, including the new psychoactive substances EAM-2201 and U-47700, were found exclusively in larvae and hair. The benzodiazepine etizolam was detected only in liver, lungs, and stomach contents, possibly resulting from characteristic tissue distribution in humans and/or larvae. Conclusions Antemortem external hair contamination with synthetic cannabinoids from side-stream smoke and postmortem hair contamination with substances in putrefaction fluids can be supposed in these cases. Our findings suggest that supplementary information can indeed be gained from analyzing larvae additional to those human specimens that are typically used for toxicological analysis after extensive postmortem decomposition. Nevertheless, these results represent merely two cases, requiring in-depth studies to determine whether such findings can identify acute intoxications as possible causes of death.

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