Illicit and Counterfeit Drug Analysis by Morphologically Directed Raman Spectroscopy

Morphologically directed Raman spectroscopy (MDRS) is a novel tool for the forensic analysis of illicit and counterfeit drug samples. MDRS combines Raman microspectroscopy with automated particle imaging so that physical and chemical information about the components of a mixture sample can be obtained. Results of automated particle imaging are used to determine samples for Raman analysis. The use of MDRS for these types of samples can be employed for both forensic investigations and adjudications of cases. The method provides insight about the physical and chemical composition of the sample, as well as about manufacturing and sample history. Here, MDRS was used in four different illicit and counterfeit drug analyses: (1) examination of a multicomponent drug mixture where the results could be used for comparative source attribution, (2) the detection of low (or trace) concentration particles in a drug sample, (3) the analysis of synthetic cathinone samples (i.e., bath salts), and (4) a study of counterfeit pharmaceutical products

User Experiences of Development of Dependence on the Synthetic Cannabinoids, 5f-AKB48 and 5F-PB-22, and Subsequent Withdrawal Syndromes

Emergence of synthetic cannabinoids (SCBs) in herbal smoking mixtures is a public health concern. New SCB’s such as 5f-AKB48 and 5F-PB-22 have been detected in French seizures and in sudden death post mortems in the US. The aim was to describe development of dependence on herbal smoking mixtures containing the SCB’s, 5f-AKB48 and 5F-PB-22 and subsequent withdrawal syndromes. Dependent users of herbal smoking mixtures known to contain the SCB’s 5f-AKB48 and 5F-PB-22 with an average Severity of Dependence Score (SDS) of 13 were interviewed using a structured guide (three males/three females). Narratives were analysed using the Empirical Phenomenological Psychological (EPP) five step method. Six themes with 68 categories emerged from the analysis. Themes are illustrated as 1) Networks and Product Availability; 2) Drivers and Motives for Use; 3) Effect and Pathways toward Dependence; 4) Poly Substance Use and Comparisons to Natural Cannabis; 5) Dependence and Withdrawal and 6) Self-detoxification Attempts. Two higher levels of abstraction above these theme-levels emerged from the data, with sole use of herbal smoking mixtures containing 5f-AKB48 and 5F-PB-22 centering on the interplay between intense cravings, compulsive all-consuming seeking, use and re-dose behaviours, and fear of the psychiatric and self-harms caused when in withdrawal. This is the first study describing dependence and withdrawal experiences in users dependent on 5f-AKB48 and 5F-PB-22. Given the potential for adverse psychiatric and physical consequences of dependent use, further development of specific clinical responses and clinical research around toxicity and withdrawal severity are warranted

Assessing the experience of using synthetic cannabinoids by means of interpretative phenomenological analysis

BACKGROUND: New psychoactive substances (NPS) have been increasingly consumed by people who use drugs in recent years, which pose a new challenge for treatment services. One of the largest groups of NPS is synthetic cannabinoids (SCs), which are intended as a replacement to cannabis. While there is an increasing body of research on the motivation and the effects associated with SC use, little is known about the subjective interpretation of SC use by the people who use drugs themselves. The aim of this study was to examine the experiences and personal interpretations of SC use of users who were heavily dependent on SC and are in treatment. METHODS: A qualitative research method was applied in order to explore unknown and personal aspects of SC use. Semi-structured interviews were conducted with six participants who had problematic SC use and entered treatment. The research was conducted in Hungary in 2015. We analyzed data using interpretative phenomenological analysis (IPA). RESULTS: Participants perceived SCs to be unpredictable: their initial positive experiences quickly turned negative. They also reported that SCs took over their lives both interpersonally and intrapersonally: the drug took their old friends away, and while initially it gave them new ones, in the end it not only made them asocial but the drug became their only friend, it hijacked their personalities and made them addicted. CONCLUSIONS: Participants experienced rapid development of effects and they had difficulties interpreting or integrating these experiences. The rapid alteration of effects and experiences may explain the severe psychopathological symptoms, which may be important information for harm reduction and treatment services. Since, these experiences are mostly unknown and unpredictable for people who use SCs, a forum where they could share their experiences could have a harm reducing role. For a harm reduction point of view of SCs, which are underrepresented in literature, it is important to emphasize the impossibility of knowing the quantity, purity, or even the number of different SC compounds in a particular SC product. Our study findings suggest that despite the adverse effects, including a rapid turn of experiences to negative, rapid development of addiction and withdrawal symptoms of SCs, participants continued using the drug because this drug was mostly available and cheap. Therefore, a harm reduction approach would be to make available and legal certain drugs that have less adverse effects and could cause less serious dependence and withdrawal symptoms, with controlled production and distribution (similarly to cannabis legalization in the Netherlands)

Phase I Hydroxylated Metabolites of the K2 Synthetic Cannabinoid JWH-018 Retain In Vitro and In Vivo Cannabinoid 1 Receptor Affinity and Activity

K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from Δ(9)-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation of novel, biologically active metabolites may be responsible for the distinct effects associated with K2 use. The present study proposes that K2's high adverse effect occurrence is due, at least in part, to distinct JWH-018 metabolite activity at the cannabinoid 1 receptor (CB1R).JWH-018, five potential monohydroxylated metabolites (M1-M5), and one carboxy metabolite (M6) were examined in mouse brain homogenates containing CB1Rs, first for CB1R affinity using a competition binding assay employing the cannabinoid receptor radioligand [(3)H]CP-55,940, and then for CB1R intrinsic efficacy using an [(35)S]GTPγS binding assay. JWH-018 and M1-M5 bound CB1Rs with high affinity, exhibiting K(i) values that were lower than or equivalent to Δ(9)-THC. These molecules also stimulated G-proteins with equal or greater efficacy relative to Δ(9)-THC, a CB1R partial agonist. Most importantly, JWH-018, M2, M3, and M5 produced full CB1R agonist levels of activation. CB1R-mediated activation was demonstrated by blockade with O-2050, a CB1R-selective neutral antagonist. Similar to Δ(9)-THC, JWH-018 and M1 produced a marked depression of locomotor activity and core body temperature in mice that were both blocked by the CB1R-preferring antagonist/inverse agonist AM251.Unlike metabolites of most drugs, the studied JWH-018 monohydroxylated compounds, but not the carboxy metabolite, retain in vitro and in vivo activity at CB1Rs. These observations, combined with higher CB1R affinity and activity relative to Δ(9)-THC, may contribute to the greater prevalence of adverse effects observed with JWH-018-containing products relative to cannabis

Health and social problems associated with recent Novel Psychoactive Substance (NPS) use amongst marginalised, nightlife and online users in six European countries.

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland (n = 3023). Some respondents were unable to categorise NPS they had used. Use of ‘herbal blends’ and ‘synthetic cannabinoids obtained pure’ was most reported in Germany, Poland and Hungary, and use of ‘branded stimulants’ and ‘stimulants/empathogens/nootropics obtained pure’ was most reported in the Netherlands. Increased heart rate and palpitation, dizziness, anxiety, horror trips and headaches were most commonly reported acute side effects. Marginalised users reported substantially more acute side effects, more mid- and long-term mental and physical problems, and more social problems. Development of country-specific NPS awareness raising initiatives, health and social service needs assessments, and targeted responses are warranted

Randomised trials in context: practical problems and social aspects of evidence-based medicine and policy

Randomised trials can provide excellent evidence of treatment benefit in medicine. Over the last 50 years, they have been cemented in the regulatory requirements for the approval of new treatments. Randomised trials make up a large and seemingly high-quality proportion of the medical evidence-base. However, it has also been acknowledged that a distorted evidence-base places a severe limitation on the practice of evidence-based medicine (EBM). We describe four important ways in which the evidence from randomised trials is limited or partial: the problem of applying results, the problem of bias in the conduct of randomised trials, the problem of conducting the wrong trials and the problem of conducting the right trials the wrong way. These problems are not intrinsic to the method of randomised trials or the EBM philosophy of evidence; nevertheless, they are genuine problems that undermine the evidence that randomised trials provide for decision-making and therefore undermine EBM in practice. Finally, we discuss the social dimensions of these problems and how they highlight the indispensable role of judgement when generating and using evidence for medicine. This is the paradox of randomised trial evidence: the trials open up expert judgment to scrutiny, but this scrutiny in turn requires further expertise