Validation of an LC-MS/MS method for the quantitative analysis of 1P-LSD and its tentative metabolite LSD in fortified urine and serum samples including stability tests for 1P-LSD under different storage conditions

A variety of hallucinogens of the lysergamide type has emerged on the drug market in recent years and one such uncontrolled derivative of lysergic acid diethylamide (LSD) is 1 propionyl LSD (1P LSD). Due to the high potency of LSD and some of its derivatives (common doses: 50-200 µg), sensitive methods are required for the analysis of biological samples such as serum and urine. The occurrence of an intoxication case required the development of a fully validated, highly sensitive method for the quantification of 1P LSD and LSD in urine and serum using LC-MS/MS. Given that LSD is unstable in biological samples when exposed to light or elevated temperatures, we also conducted stability tests for 1P LSD in urine and serum under different storage conditions. The validation results revealed that the analysis method was accurate and precise with good linearity over a wide calibration range (0.015-0.4 ng mL-1). The limit of detection (LOD) and the lower limit of quantification (LLOQ) of 1P-LSD and LSD in serum and urine were 0.005 ng mL-1 and 0.015 ng mL-1, respectively. The stability tests showed no major degradation of 1P LSD in urine and serum stored at -20 °C, 5 °C or at room temperature for up to five days, regardless of protection from light. However, LSD was detected in all samples stored at room temperature showing a temperature-dependent hydrolysis of 1P LSD to LSD to some extent (up to 21% in serum). Serum samples were particularly prone to hydrolysis possibly due to enzymatically catalyzed reactions. The addition of sodium fluoride prevented the enzymatic formation of LSD. The method was applied to samples obtained from the intoxication case involving 1P LSD. The analysis uncovered 0.51 ng mL-1 LSD in urine and 3.4 ng mL-1 LSD in serum, whereas 1P LSD remained undetected. So far pharmacokinetic data of 1P LSD is missing, but with respect to the results of our stability tests and the investigated case rapid hydrolysis to LSD in vivo seems more likely than instabilities of 1P¬LSD in urine and serum samples

Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones

Introduction and AimsThe current study documents the characteristics associated with the use of two novel psychoactive substances: synthetic cannabinoids and synthetic cathinones.Design and MethodsNationally representative samples of students in 8th (n = 9665), 10th (n = 10 655) and 12th (n = 10 057) grades across the US were included in the Monitoring the Future study from 2012 to 2014.ResultsThere were relatively few differences in prevalence based on sociodemographic characteristics, although boys were at greater risk for use of synthetic cannabinoids in 12th grade (used by 10.3% of boys and 6.4% of girls) and for use of synthetic cathinones in 10th grade (used by 1.0% of boys and 0.4% of girls). Synthetic drug use was also associated with truancy and use of cigarettes, alcohol, and marijuana.Discussion and ConclusionsPrevention and intervention efforts for novel psychoactive substance use should focus primarily on polysubstance users and youth who are disengaged from school.[Patrick M, O’Malley P, Kloska D, Schulenberg J, Johnston L, Miech R, Bachman J. Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones. Drug Alcohol Rev 2016;35:586–590]Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134241/1/dar12372.pd

Acute myocardial infarction, associated with the use of a synthetic adamantyl-cannabinoid: a case report

BACKGROUND: “Legal highs” are novel psychoactive substances that have evaded statutory control. Synthetic cannabinoid compounds with adamantane moieties have recently been identified, which have high potency at target receptors and are undetectable on conventional toxicology testing. However, little is known about any harmful effects, and their potential to cause serious ill health. We describe a case of myocardial infarction following the use of this class of drug. CASE PRESENTATION: We report the case of a 39-year-old man admitted after an out-of-hospital cardiac arrest, in whom ECG and elevated cardiac enzymes confirmed ST-elevation myocardial infarction. Normal coronary perfusion was restored after thrombectomy and coronary artery stenting. In the hours preceding his admission, the patient is known to have consumed the legal high product “Black Mamba”. Subsequent urine testing confirmed the presence of an adamantyl-group synthetic cannabinoid, whilst cannabis, cocaine, amphetamines and other drugs of abuse were not detected. CONCLUSION: The use of legal highs is being increasingly recognised, but the chemical compositions and physiological effects of these drugs are poorly characterised and are continually changing. Synthetic cannabinoids, rarely identified on toxicological testing, can be linked to serious adverse cardiovascular events. This case highlights the importance of testing for novel psychoactive compounds, and recognising their potential to cause life-threatening conditions

New/emerging psychoactive substances and associated psychopathological consequences

Submitted 24 November 2018, Revised 18 June 2019, Accepted 26 June 2019, Published online 22 July 2019BackgroundThe 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.MethodsNPS 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.ResultsUsing 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.ConclusionsThe 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.Peer reviewe

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

Update of the Scientific Opinion on opium alkaloids in poppy seeds

The CONTAM Panel wishes to thank the hearing experts: Pavel Cihlar, Daniel Doerge and Vaclav Lohr for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data on opium alkaloids in food, and supported the data collection for the Comprehensive European Food Consumption Database. Adopted: 22 March 2018 Reproduction of the images listed below is prohibited and permission must be sought directly from the copyright holder:Figure A.1 in Appendix A: © Elsevier.Peer reviewedPublisher PD

Annual banned-substance review: Analytical approaches in human sports drug testing.

A number of high profile revelations concerning anti-doping rule violations over the past 12 months have outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti-doping system. At this time, the necessity to enhance, expand, and improve analytical test methods in response to the substances outlined in the World Anti-Doping Agency (WADA) Prohibited List represents an increasingly crucial task for modern sports drug testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug testing assays, drug elimination profiles, and alternative sample matrices, together with recent advances in instrumental developments. This annual banned-substance review evaluates literature published between October 2017 and September 2018 offering an in-depth evaluation of developments in these arenas and their potential application to substances reported in WADA's 2018 Prohibited List