Technical report on 1-phenyl-2- (pyrrolidin-1-yl)pentan-1-one (α-pyrrolidinovalerophenone, α-PVP)

This publication presents the data and findings of the risk assessment on α-PVP (1-phenyl- 2-(1-pyrrolidinyl)-1-pentanone), carried out by the extended Scientific Committee of the EMCDDA on 18 November 2015. α-PVP is the eleventh new psychoactive substance to be risk assessed under the terms of Council Decision 2005/387/JHA. On the basis of the Risk Assessment Report — and on the initiative of the European Commission — on 27 June 2016, the Council decided that α-PVP should be subject to control measures across the Member States

Technical report on 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe). Annex 2 to the “Risk Assessment Report of a new psychoactive substance: 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe)”.

This report forms the basis for a risk assessment, which is convened by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under auspices of its Scientific Committee and other externally invited experts. Furthermore, the Commission, Europol and the EMA are invited to participate in the risk assessment meetings. The risk assessment takes into account all factors that, according to the 1961 United Nations Single Convention on Narcotic Drugs or the 1971 United Nations Convention on Psychotropic Substances, would warrant the placing of a substance under international control (see http://www.emcdda.europa.eu/html.cfm/index16776EN.html)

N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylarnine Analogues

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5- dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotonin receptors showed that most of the compounds had the highest affinity at the 5-HT2 family receptors. Substitution at the para position of the benzyl group resulted in reduced affinity, whereas substitution in either the ortho or the meta position enhanced affinity. In general, introduction of a large lipophilic group improved affinity, whereas functional activity often followed the opposite trend. Tests of the compounds for functional activity utilized intracellular Ca2+ mobilization. Function was measured at the human 5-HT2A, 5-HT2B, and 5-HT2C receptors, as well as at the rat 5-HT2A and 5-HT2C receptors. There was no general correlation between affinity and function. Several of the tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM), but most were partial agonists. Tests in the mouse head twitch assay revealed that many of the compounds induced the head

Exposure of benthic invertebrates to sediment vibration: From laboratory experiments to outdoor simulated pile-driving

This is the final version of the article. Available from Acoustical Society of America via the DOI in this record.Fourth International Conference on the Effects of Noise on Aquatic Life, Dublin, Ireland, 10-16 July 2016Activities directly interacting with the seabed, such as pile-driving, can produce vibrations that have the potential to impact benthic invertebrates within their vicinity. This stimuli may interfere with crucial behaviors such as foraging and predator avoidance, and the sensitivity to vibration is largely unknown. Here, the responsiveness of benthic invertebrates to sediment vibration is discussed in relation to laboratory and semi-field trials with two marine species: the mussel (Mytilus edulis) and hermit crab (Pagurus bernhardus). Sensory threshold curves were produced for both species in controlled laboratory conditions, followed by small-scale pile-driving exposures in the field. The merits of behavioral indicators are discussed, in addition to using physiological measures, as a method of determining reception and measuring responses. The measurement and sensors required for sediment vibration quantification are also discussed. Response and threshold data were related to measurements taken in the vicinity of anthropogenic sources, allowing a link between responsiveness and actual operations. The impact of pile-driving on sediment-dwelling invertebrates has received relatively little research, yet the data here suggest that such activities are likely to impact key coastal species which play important roles within the marine environment.LR would like to thank the organizers and sponsors of the 2016 conference for supporting her attendance for which she is extremely grateful. This study was partially funded by a research award from the Malacological Society of London to LR. The authors would also like to acknowledge Defra and NERC who funded the laboratory and field work aspects respectively, and the staff at the OREC field site, Blyth

First Reported Fatalities Associated with the 'Research Chemical' 2-Methoxydiphenidine

2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework. The 2-, 3- and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework

Analytical characterization of bioactive N-benzyl-substituted phenethylamines and 5-methoxytryptamines

RationaleSubstances based on the N-(2-methoxybenzyl)phenethylamine template ('NBOMe' derivatives) play an important role in medicinal research but some of these derivatives have also appeared as 'research chemicals' for recreational use which has attracted attention worldwide. A major challenge associated with newly emerging substances includes the lack of analytical data and the ability to correctly identify positional isomers.Methods Six N-benzylphenethylamines based on the 2,5-dimethoxy-4-iodophenethylamine structure ('25I') and twelve substituted N-benzyl-5-methoxytryptamines ('5MT') have been prepared and extensively characterized. Techniques used for characterization were gas chromatography/ion trap mass spectrometry in electron and chemical ionization mode, liquid chromatography/diode array detection (DAD), infrared spectroscopy, electrospray high mass accuracy quadrupole time-of-flight tandem mass spectrometry, and triple quadrupole tandem mass spectrometry.ResultsThe characterization of 18 'NBOMe' compounds provided a comprehensive collection of chromatographic and spectral data. Four groups of three positional isomers, i.e. 25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25I-NB3B, 25I-NB4B and their 5-methoxytryptamine counterparts, were included and assessed for ability to obtain differentiation. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine (CF3, F, CH3, Cl, I, SCH3) were also studied.Conclusions The implementation of mass spectral techniques was helpful for the differentiation between isomers, for example, when considering the difference in a number of ion ratios. This was considered beneficial in cases where chromatographic separation was only partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD analysis was also found to be valuable for this particular purpose, which confirmed the integrative value of complementary techniques used in areas related to forensic toxicology

Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD).

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a 'research chemical' in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A -receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025-0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50  = 349.6 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd

Technical report on N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyrylfentanyl; 4F-iBF). Annex 1 to the Risk Assessment Report on N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide (4-fluoroisobutyrylfentanyl; 4F-iBF)

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances

Technical report on N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]oxolane-2-carboxamide (tetrahydrofuranylfentanyl; THF-F). Annex 1 to the Risk Assessment Report on N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]oxolane-2- carboxamide (tetrahydrofuranylfentanyl).

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances

Technical report on 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide (CUMYL-4CN-BINACA). Annex 1 to the Risk Assessment Report on 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3- carboxamide (CUMYL-4CN-BINACA).

In accordance with Article 6 of Council Decision 2005/387/JHA on the information exchange, risk assessment and control of new psychoactive substances