Amira Guirguis

Analysis of ‘legal high’ substances and common adulterants using handheld spectroscopic techniques

The identification of ‘legal highs’ is challenging as they often do not match their label claim and contain a wide range of impurities and/or adulterants. In addition, there is a need for techniques to be on-site, rapid and non-destructive. The feasibility of using the in-built algorithms of handheld near-infrared (NIR), Raman and attenuated total reflectance Fourier transform-infrared (ATR-FT-IR) spectroscopy for the identification of ‘legal high’ substances was investigated. Spectral libraries were constructed using three substances found in ‘legal highs’ (i.e., dextromethorphan, 2-aminoindane and lidocaine) and their 50 : 50 mixtures with caffeine. Model dilution mixtures with caffeine (i.e., 5–95% m/m) and seven ‘legal high’ Internet products were used to test the method. The ‘legal high’ constituents in most of the model mixtures were identified within a minimum range of 30–60% m/m for NIR, 20–75% m/m for Raman, and 41–85% m/m for ATR-FT-IR. This demonstrates that simple library mixtures could be used to identify test substances when the concentrations are variable. Below and above these levels, the test mixtures often correlated to the component in higher concentration. Collectively, the instruments identified the main constituents in the seven Internet products with varying correlation criteria. The NIR and ATR-FT-IR provided complementary information compared to Raman when carbohydrate cutting agents were added to the product, yet the Raman showed a high fluorescence signal for three products hindering identification. These initial studies indicate the suitability of three complementary techniques for rapid identification of ‘legal high’ products. Further development of spectral libraries, algorithms, and use of alternative Raman excitation wavelengths is needed to provide adequate tools for in-field analysis by non-experts.

Intended and Unintended Use of Cathinone Mixtures

Cathinones are one of the most popular categories of new psychoactive substances (NPS) consumed. Cathinones have different pharmacological activities and receptor selectivity for monoamine transporters based on their chemical structures. They are incorporated into NPS mixtures and used with other NPS or ‘traditional’ drugs. Cathinone use represents significant health risks to individuals and is a public health burden.

Survey of knowledge of legal highs (novel psychoactive substances) amongst London pharmacists

Purpose – The purpose of this paper is to determine pharmacists’ knowledge of legal highs (novel psychoactive substances (NPS)). Design/methodology/approach – A questionnaire was handed out at two London pharmacist continuing education events in mid-2014. These events update pharmacists about developments of interest/relevance to the profession and to improve their practice. A total of 54 forms were returned; a response rate of 26 percent. Findings – Most pharmacists had poor knowledge of NPS and many considered that NPS were not important to their work, with few having had to advise customers in this area. Despite this, the majority thought that they had insufficient information about NPS. There was a negative correlation between the age of the pharmacist and knowledge of NPS. Research limitations/implications – The sample is a self-selected one drawn from registered pharmacists working in community pharmacies in northwest London, and thus does not include hospital pharmacies. Self-selection means that r...

Drowning in diversity? A systematic way of clustering and selecting a representative set of new psychoactive substances

New psychoactive substances (NPS) can be generally described as a set of compounds that have been designed to mimic the effects of illegal recreational drugs, but are not subject to restriction or control with respect to existing regulations and legislation. In recent years, the number and chemical diversity of emergent NPS has increased substantially, and regulators have struggled to develop methods for accurate detection of NPS at the same rate. Existing approaches to NPS classification are pragmatic and/or semi-systematic and do not lend themselves to objective spectroscopic classification of emergent NPS. As such, this research discusses the identification of a systematic NPS classification based on chemical structures. A set of 478 NPS were grouped according to the similarity between their chemical structural features using hierarchical clustering and a maximum common substructure of 9 atoms, which included both hydrogen and heavy atoms. The rationale for including hydrogen atoms is that accurate spectroscopic identification of NPS will be dependent upon variations in substitution patterns in the molecules. This analysis generated 79 clusters, arising from 21 superclusters. The medoid substances of each cluster were used to form a dataset that was representative of the chemical space encompassed by known NPS. Subsequent categorisation of a test set of NPS showed that the test substances were assigned to an appropriate cluster when the Tanimoto similarity coefficient between the cluster medoid and the test substance was at least 0.5. This indicates that the cluster medoids could be used for assignment of emerging NPS to systematically-defined categories based on chemical structure. These medoids will also aid in the prediction of spectroscopic properties for emergent NPS, which will be invaluable for structure-based classifications and development of methods for detection of emerging NPS.

New psychoactive substances: a public health issue

The recreational drug scene has evolved dramatically over the last decade with the emergence of new psychoactive substances (NPS) supplementing rather than replacing the known drug repertoire. NPS are natural and synthetic recreational molecules, which mimic the effects of traditional drugs of abuse (TDA) (e.g. cocaine, amphetamine and ecstasy), yet they are not internationally controlled under the United Nations 1961 and 1971 conventions. The wide prevalence of NPS and complex nature inherent in NPS pose public health risks and represent great challenges to policymakers, front-line staff and healthcare professionals (HCPs). Evidence shows that NPS have caused global problems, shortand long-term health harms, and they are ‘more than a one night wonder’. New psychoactive substances are characterised by a complex life cycle. They are initially synthesised in bulk by chemical companies based in China and India; shipped by air or sea to Europe; sold directly in the illicit drug market or cut; and packaged as ‘research chemicals’, food supplements or branded products. These labels support the covert marketing techniques undertaken by clandestine chemists and circumvent international legislation. NPS are sold online or in headshops. They first appear on the deep web targeting NPS wholesalers, and then, the surface web via professional-like websites backed up with multibuy deals. During the first phase, the drug is mainly purchased and consumed by psychonauts (explorers of mind-altering activities using new NPS), who share their experiences on drug fora. This is followed by a displacement or substitution of a less popular NPS, death or birth of a new NPS. Unlike pharmaceuticals, NPS are not produced in line with good manufacturing practices or any type of quality assurance or clinical testing. They are tested directly on the consumer. New psychoactive substances epidemic cycles evidence their prevalence among all age groups and defined societal sectors such as school and university students, MSM (men who have sex with men), heroin injectors, prisoners and music festival goers. Their wide popularity is believed to be due to their perceived ‘legal’ status, potential for new experiences and desirable effects (e.g. increased libido, euphoria) wide availability, relative cheapness and lack of detection. The umbrella of NPS has recently widened (>740 NPS) to include not only newly invented drugs but re-emerging failed pharmaceutical patents, diverted use of prescription-only, pharmacyonly and over-the-counter medicines and the so-called smart drugs (cognitive, image, mood & behaviour and sexual enhancers; and muscle and weight-loss drugs). New psychoactive substances pose significant public health concerns. Their complex pharmacological profile results in a combination of psychoactive effects (e.g. both cocaine and MDMA-like effects) previously only possible through cocktails of TDA. Clinical challenges faced by HCPs include the different routes of administration of NPS, inconsistent content in and potency of branded products, unclaimed active ingredients, frequent dosing, poly-drug use, presence of complex mixtures, lack of knowledge of their toxicodynamics and toxicokinetics, different formulations and unknown knowledge of the consequences of chronic use. On presentation to emergency departments, users rarely know what they have taken, which reduces the effectiveness of subsequent clinical interventions. Another major challenge to HCPs is how to categorise NPS, which often leads to the adoption of a symptommanagement approach, particularly with the lack of information via professional databases such as Toxbase. Management should preferably be tailored to patients and supported by a multidisciplinary approach. Regular users with problems of poly-drug use may also suffer from a dual diagnosis, that is an addiction problem associated with psychiatric disorders. Users may also suffer from secondary issues, for example cellulitis resulting from injecting NPS. Available classifications such as those suggested in the NEPTUNE guidelines and the Drug Wheel offer a great support to HCPs, yet a regular update is necessary to map the new NPS on the drug scene. Limitations also include the ability of these tools to classify NPS from their complex names, for example discriminating between the opioid U-47,700 and the classical cannabinoid HU-210. Another challenge faced by HCPs is that

Detection of Newly Emerging Psychoactive Substances Using Raman Spectroscopy and Chemometrics

A novel approach for the identification of New Psychoactive Substances (NPS) by means of Raman spectroscopy coupled with Principal Components Analysis (PCA) employing the largest dataset of NPS reference materials to date is reported here. Fifty three NPS were selected as a structurally diverse subset from an original dataset of 478 NPS compounds. The Raman spectral profiles were experimentally acquired for all 53 substances, evaluated using a number of pre-processing techniques, and used to generate a PCA model. The optimum model system used a relatively narrow spectral range (1300–1750 cm−1) and accounted for 37% of the variance in the dataset using the first three principal components, despite the large structural diversity inherent in the NPS subset. Nonetheless, structurally similar NPS (i.e., the synthetic cannabinoids FDU-PB-22 & NM-2201) grouped together in the PCA model based on their Raman spectral profiles, while NPS with different chemical scaffolds (i.e., the benzodiazepine flubromazolam and the cathinone α-PBT) were well delineated, occupying markedly different areas of the three-dimensional scores plot. Classification of NPS based on their Raman spectra (i.e., chemical scaffolds) using the PCA model was further investigated. NPS that were present in the initial dataset of 478 NPS but were not part of the selected 53 training set (validation set) were observed to be closely aligned to structurally similar NPS within the generated model system in all cases. Furthermore, NPS that were not present in the original dataset of 478 NPS (test set) were also shown to group as expected in the model (i.e., methamphetamine and N-ethylamphetamine). This indicates that, for the first time, a model system can be applied to potential ‘unknown’ psychoactive substances, which are new to the market and absent from existing chemical libraries, to identify key structural features to make a preliminary classification. Consequently, it is anticipated that this study will be of interest to the broad scientific audience working with large structurally diverse chemical datasets and particularly to law enforcement agencies and associated scientific analytical bodies worldwide investigating the development of novel identification methodologies for psychoactive substances.

Synthetic Cathinones—Prevalence and Motivations for Use

This chapter considers the prevalence of and motivations for use of synthetic cathinones. As part of the scene-setting, the availability, legal status, numbers of cathinones, number and quantities confiscated are reviewed. This leads to the first substantive section of the chapter—an epidemiological investigation of the nature and extent of what is known about the use of these molecules. The second major section is more qualitative in its approach to understanding motivations for the use of any drug, Novel Psychoactive Substances (NPS), and then synthetic cathinones. An examination is conducted of how cathinones may be compared to other stimulants and why particular cathinones may be preferred to others. The converse situation is then examined, what might be the motivations and reasons for ceasing to take cathinones and why this may not be a rational decision. A brief examination of the consequences of ceasing versus continued use is presented. As it is very likely that further synthetic cathinones will continue to emerge, it is important to gain a much fuller insight into what motivates or causes individuals to use or cease using these molecules, so that communities and societies can respond in appropriate ways to the varying challenges that face them and their citizens.

CHAPTER 9:Raman Spectroscopy for the Analysis of Novel Psychoactive Substances (NPS)

In this chapter, the use of Raman spectroscopy, a light-based scattering technique, will be examined for its chemical detection of novel psychoactive substances (NPS) in forensic applications. As it is a vibrational technique based on changes in polarisability, Raman spectroscopy has been shown to decipher NPS chemical analogues as well as the NPS from cutting agents and adulterants present in associated products. Analysis can be done in the laboratory or in-field using handheld versions, in which the latter often have in-built matching algorithms for a quick response for non-experts. Analysis can often be carried out through the product packaging (i.e., glass and plastic), however the presence of impurities or cutting agents can lead to high levels of fluorescence which often masks the instrument response from an NPS. Methods for overcoming fluorescence interference includes spectral pre-processing, use of lower energy source radiation, and Surface Enhanced Raman Spectroscopy (SERS). In particular, the availability of handheld Raman spectrometers and the signal enhancements observed for SERS show much potential for application in crime scene investigations.

Exploration of the Use of New Psychoactive Substances by Individuals in Treatment for Substance Misuse in the UK

Substance misuse services need to meet the growing demand and needs of individuals using new psychoactive substances (NPS). A review of the literature identified a paucity of research regarding NPS use by these individuals and UK guidelines outline the need for locally tailored strategies. The purpose of this qualitative study was to identify and explore key themes in relation to the use of NPS by individuals receiving community treatment for their substance use. Electronic records identified demographics and semi-structured interviews were undertaken. A thematic analysis of transcripts identified a variety of substance use histories; 50% were prescribed opiate substitutes and 25% used NPS as a primary substance. All were males, age range 26–59 years (SD = 9), who predominantly smoked cannabinoids and snorted/injected stimulant NPS. The type of NPS used was determined by affordability, availability, side-effect profile and desired effects (physical and psychological: 25% reported weight loss as motivation for their use). Poly-pharmacy, supplementation and displacement of other drugs were prevalent. In conclusion, NPS use and associated experiences vary widely among people receiving substance use treatment. Development of effective recovery pathways should be tailored to individuals, and include harm reduction strategies, psychosocial interventions, and effective signposting. Services should be vigilant for NPS use, “on top” use and diversion of prescriptions.

Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review

Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies.