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This study was conducted in order to evaluate prospective health care professionals’ (HCPs) awareness and attitudes regarding new psychoactive substances (NPSs) in the context of their future role in the prevention and treatment of NPS overdose and addiction. Correlates of NPS perception and use were also examined. This cross-sectional survey was performed on 490 students of the Faculty of Medicine, Novi Sad, Serbia, during 2017. NPS awareness was better in pharmacy students (IRR: 1.926, CI: 1.173–3.163, p = 0.010) than in medicine students—pharmacy students recognized 92.6% more NPS names than their peers studying medicine. Female students knew 36.5% less NPS names than their male colleagues (IRR: 0.635, CI: 0.399–1.013, p = 0.049). Number of NPS names students knew was rising by 15.9% with each age group—the higher the age, the larger the number of NPSs they were aware of (IRR: 1.159, CI: 1.025–1.310, p = 0.018). Students who had used marijuana knew 52.6% more NPS names than those who had never had experience with cannabis (IRR: 1.526, CI: 0.953–2.445, p = 0.049). Although a high number of future HCPs claimed to know what NPSs are, numerous misconceptions were noticed. Further educational efforts are necessary to improve their awareness and attitudes regarding NPSs.

Background To counteract the spread of new psychoactive substances (NPS) and to prevent the emergence of novel substances, specifically designed as a response to the legal control of individual substances, a new law was introduced in Germany in 2016: the New Psychoactive Substances Act (NpSG). The NpSG combines a generic approach with the waiver of criminal liability for the acquisition and possession of NPS for personal use, which is a novelty in German narcotics law. The present study aimed at exploring the impact of the introduction of the NpSG from three different perspectives—NPS users, staff of addiction care facilities, and members of law enforcement authorities—to better understand the dynamics surrounding such a change in legislation and to contribute to the body of international experience in dealing with NPS. Methods Semi-structured narrative interviews were conducted with a total of 193 representatives of the three different groups affected by the law. These interviews included questions on perceived changes associated with the introduction of the NpSG as well as questions on opinions regarding legal and criminal policy issues. The analysis was carried out using qualitative content analysis according to Mayring. Results Most interviewees welcomed the non-criminalisation approach of the NpSG but also noticed that, in practice, not much has changed for users. Nevertheless, the changes in legislation have had an impact on the market. For example, novel substances have emerged circumventing the new legislation. According to users, this has led some to reduce NPS use and others to adopt more hazardous consumption patterns. Overall, most respondents did not expect the introduction of the NpSG to bring any significant changes. Conclusions Although the idea of non-criminalisation inherent to the NpSG is appreciated and the generic approach has been well implemented in the law, thus covering a wide range of substances, the introduction of the law—perhaps for that very reason—has also had unintended and negative consequences, taking the cat-and-mouse game to the next level. To end the game, or at least to defuse the game situation, a combination of different strategies will be necessary, with legislation always playing a key role.

New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.

The present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects. NPS have been identified through an innovative crawling/navigating software, called the 'NPS.Finder®', created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available. Using the 'NPS.Finder®' approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines. The ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.

•Summary of fatalities with findings of new psychoactive substances previously described in scientific literature.•Overview of postmortem concentrations of new psychoactive substances determined in various biological matrices.•The compiled data assist forensic toxicologists with the interpretation of death cases involving new psychoactive substances. In the last decades, more and more new psychoactive substances (NPS) were introduced on the drug market which were sold as “legal” alternatives for classic drugs and misused medications. Due to an increased number of available substances and a growing utilization by users of common drugs but also by inexperienced users because of the supposed “legal” status, also undesired adverse effects of these NPS, at worst leading to death, became apparent. This review summarizes fatalities previously described in scientific literature which were attributed to the use of NPS or such cases, in which intake of NPS was proven or even assumed to contribute to death. This summary includes an overview of substances involved (particularly synthetic cannabinoids (“spice”), novel opioids and synthetic cathinones (“bath salts”)) as well as of postmortem concentrations determined in various biological matrices. The compiled data assist forensic toxicologists with the interpretation of death cases involving NPS.

Graphical abstract

Novel synthetic opioids continue to emerge on recreational drug markets worldwide. In response to legislative bans on fentanyl analogues, non-fentanyl structural templates, such as 2-benzylbenzimidazoles (‘nitazenes’), are being exploited to create new μ-opioid receptor (MOR) agonists. Here, we pharmacologically characterize an emerging cyclic analogue of etonitazene, called N- pyrrolidino etonitazene (etonitazepyne), using in vitro and in vivo methods. A series of analytically confirmed fatalities is described to complement preclinical findings. Radioligand binding assays in rat brain tissue revealed that N- pyrrolidino etonitazene has high affinity for MOR (Ki = 4.09 nM) over δ-opioid (Ki = 959 nM) and κ-opioid (Ki = 980 nM) receptors. In a MOR-β-arrestin2 activation assay, N- pyrrolidino etonitazene displayed high potency (EC 50  = 0.348 nM), similar to etonitazene (EC 50  = 0.360 nM), and largely exceeding the potencies of fentanyl (EC 50  = 14.9 nM) and morphine (EC 50  = 290 nM). When administered s.c. to male Sprague Dawley rats, N- pyrrolidino etonitazene induced opioid-like antinociceptive, cataleptic, and thermic effects. Its potency in the hot plate test (ED 50  = 0.0017 mg/kg) was tenfold and 2,000-fold greater than fentanyl (ED 50  = 0.0209 mg/kg) and morphine (ED 50  = 3.940 mg/kg), respectively. Twenty-one overdose fatalities associated with N- pyrrolidino etonitazene were found to contain low blood concentrations of the drug (median = 2.2 ng/mL), commonly in the context of polysubstance use. N- Pyrrolidino etonitazene was reported as a cause of death in at least two cases, demonstrating toxicity in humans. We demonstrate that N- pyrrolidino etonitazene is an extremely potent MOR agonist that is likely to present high risk to users. Continued vigilance is required to identify and characterize emergent 2-benzylbenzimidazoles, and other non-fentanyl opioids, as they appear in the marketplace.

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.

In addition to well-known traditional synthetic illicit drugs like cocaine, amphetamines, and heroin, an increasing number of new psychoactive substances (NPS) are appearing on the global drug market. Among them, cathinones represent a prominent class. These amphetamine-like compounds contain a stereogenic center, resulting in the possible presence of two enantiomers. Pure enantiomers of cathinone derivatives are not commonly available, and their production is cost-intensive. Thus, there is very little knowledge about the possible distinct effects of single enantiomers of cathinones. The objective of this study was to evaluate the stability of a set of eight cathinone derivatives, namely 3-methylethcathinone, 3-methylmethcathinone, 4-methylethcathinone, 4-methylmethcathinone, ethylone, 3,4-trimethylene-α-ethylaminovalerophenone, 3,4-tetramethylene-α-pyrrolidinovalerophenone, and 3,4-trimethylene-α-pyrrolidinobutiophenone, over a six-month period. Any racemization that may have occurred under different storage and solution conditions was monitored and compared. Pure enantiomeric fractions were collected on a multi-milligram scale using semi-preparative HPLC under isocratic normal-phase conditions. A Phenomenex Lux® i-Cellulose-5, 5 μm 250 × 10 mm column containing cellulose tris(3,5-dichlorophenylcarbamate) served as the chiral selector. The tests showed that aqueous conditions, pH, temperature, chemical structure, sunlight, and oxygen influence compound stability. The long-term storage of cathinone derivative enantiomers was found to be optimal as solids under deep-freezing conditions or in a slightly acidified solvent where they are protected from air and light.

•Carfentanil has contributed to an increase in opioids-related intoxications in recent years.•It is often detected in heroin, other street drugs and counterfeit pharmaceuticals.•Detection of carfentanil requires specific and sensitive analytical methods that are not commonly available in hospitals.•There is no particular toxic or lethal blood carfentanil concentration.•Standard naloxone doses may be insufficient to reverse carfentanil-induced respiratory depression. The use of novel synthetic opioids as recreational drugs has become a public health concern as they are implicated in numerous fatal intoxications across the world. Synthetic opioids have played a major role in the United States opioid crisis and may contribute to a similar opioid epidemic in Europe. The most prominent group of designer opioids consists of fentanyl and its analogues. At present, carfentanil is the most dangerous fentanyl derivative. It was recently detected as an adulterant to other illicit drugs and counterfeit pharmaceuticals, contributing to life-threatening hospital admissions and fatalities. Toxic exposure to carfentanil typically occurs through injection, insufflation or inhalation. Carfentanil produces similar pharmacotoxicological effects to other opioids. However, due to its extraordinary potency, reversing carfentanil-induced severe and recurring respiratory depression requires administration of multiple or higher than standard doses of naloxone. Toxicological reports indicate that carfentanil use is strongly connected to polydrug use. Detection of carfentanil requires specific and sensitive analytical methods that are not commonly available in hospitals. Since abuse of carfentanil is an emerging problem, particularly in the United States, there is an urgent need to develop new techniques for rapid determination of intoxication evoked by this drug as well as new treatment regimens for effective overdose maintenance. This review presents current knowledge on pharmacological activity of carfentanil, prevalence and patterns of use, and analytical methods of its detection. Special emphasis is given to carfentanil-related non-fatal and lethal overdose cases.