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Markus R Meyer
This review article covers English-written and PubMed-listed review articles and original studies published between January 2015 and April 2016 dealing with the toxicodynamics and toxicokinetics of new psychoactive substances. Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, NBOMes, phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on timely review articles followed by an overview and discussion on recent original studies...
October 2016: Archives of Toxicology
Natalie R Sealover, Bruce Felts, Charles P Kuntz, Rachel E Jarrard, Gregory H Hockerman, Eric L Barker, L Keith Henry
The substituted amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy), is a widely used drug of abuse that induces non-exocytotic release of serotonin, dopamine, and norepinephrine through their cognate transporters as well as blocking the reuptake of neurotransmitter by the same transporters. The resulting dramatic increase in volume transmission and signal duration of neurotransmitters leads to psychotropic, stimulant, and entactogenic effects. The mechanism by which amphetamines drive reverse transport of the monoamines remains largely enigmatic, however, promising outcomes for the therapeutic utility of MDMA for post-traumatic stress disorder and the long-time use of the dopaminergic and noradrenergic-directed amphetamines in treatment of attention-deficit hyperactivity disorder and narcolepsy increases the importance of understanding this phenomenon...
September 13, 2016: Biochemical Pharmacology
Albert Garcia-Romeu, Brennan Kersgaard, Peter H Addy
Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use...
August 2016: Experimental and Clinical Psychopharmacology
Monika Židková, Igor Linhart, Marie Balíková, Michal Himl, Lubomír Váňa, Michal Vetýška, Tomáš Páleníček, Eva Lhotková, Martin Dušek
1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation...
July 12, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Lewis Jones, Phil Reed, Andrew Parrott
AIMS: The purpose of this study was to compare the effects of mephedrone and 3,4-methylenedioxy-methamphetamine (MDMA), as reported by young recreational polydrug users. METHODS: 152 MDMA users and 81 mephedrone users were recruited through snowballing on social network sites. They completed a standard online questionnaire for either mephedrone or MDMA. The questions covered the average amount taken per session, the longest duration of usage in the last 12-months, subjective effects while on-drug, and recovery effects in the days afterwards...
July 1, 2016: Journal of Psychopharmacology
Tomáš Páleníček, Eva Lhotková, Monika Žídková, Marie Balíková, Martin Kuchař, Michal Himl, Petra Mikšátková, Martin Čegan, Karel Valeš, Filip Tylš, Rachel R Horsley
MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity (median lethal dose, LD50) in Wistar rats...
August 1, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Jacques D Nguyen, Yanabel Grant, Kevin M Creehan, Sophia A Vandewater, Michael A Taffe
The recreational use of substituted cathinones continues to grow as a public health concern in the United States. Studies have shown that extended access to intravenous (i.v.) self-administration of stimulants, such as cocaine and methamphetamine, results in escalation of drug intake relative to shorter access; however, little is known about the impact of extended access on self-administration of entactogen class stimulants such as methylone and 4-methylmethcathinone (mephedrone). Male Wistar rats were randomly assigned to short-access (ShA, 2- h) and long-access (LgA, 6- h) groups and trained to self-administer methylone or mephedrone (0...
April 5, 2016: Addiction Biology
Débora González, Marta Torrens, Magí Farré
BACKGROUND: 2C-B (Nexus) is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. OBJECTIVES: To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. METHODS: Twenty healthy recreational 2C-B users (12 women) self-administered a 20 mg dose of 2C-B...
2015: BioMed Research International
Sophia A Vandewater, Kevin M Creehan, Michael A Taffe
The intravenous self-administration (IVSA) of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in rats, with up to half of subjects failing to acquire reliable drug intake. It is unknown if this changes under long-access conditions (6 h sessions) under which the IVSA of cocaine and methamphetamine escalates. The entactogen class cathinone stimulants which exhibit MDMA-like monoamine effects in the nucleus accumbens, mephedrone (4-methylmethcathinone) and methylone (3,4-methylenedioxymethcathinone), may support more reliable IVSA but results have been mixed...
December 2015: Neuropharmacology
Rodrigo Álvarez-Ruiz, María Jesús Andrés-Costa, Vicente Andreu, Yolanda Picó
An analytical method for determining traditional and emerging drugs of abuse in particulate matter, sewage sludge and sediment has been developed and validated. A total of 41 drugs of abuse and metabolites including cocainics, tryptamines, amphetamines, arylcyclohexylamines, cathinones, morphine derivatives, pyrrolidifenones derivatives, entactogens, piperazines and other psychostimulants were selected. Samples were ultrasound extracted with McIlvaine buffer and methanol, and the extracts were cleaned up by solid phase extraction (SPE) using Strata-X cartridges...
July 31, 2015: Journal of Chromatography. A
François Chavant, Alexandra Boucher, Reynald Le Boisselier, Sylvie Deheul, Danièle Debruyne
New substances, also known as "designer drugs" or "legal highs" are increasingly available to drug users. Two hundred and fifteen hitherto unlisted substances have been notified by European Union member states since 2005. These synthetic drugs, which have been developed to side-step the legislation on drugs, are analogues or derivatives of existing drugs and medications. The availability of these "legal highs", sold on Internet under various denominations such as bath salt, plant fertilizer, chemical not intended for human use, or spice, is unlimited...
March 2015: Thérapie
Anna Rickli, Simone Kopf, Marius C Hoener, Matthias E Liechti
BACKGROUND AND PURPOSE: Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH: We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and 5-MAPDB and benzodifuran 2C-B-FLY on the human noradrenaline (NA), dopamine and 5-HT uptake transporters using HEK 293 cells that express the respective transporters...
July 2015: British Journal of Pharmacology
Daniel José Barbosa, João Paulo Capela, Rita Feio-Azevedo, Armanda Teixeira-Gomes, Maria de Lourdes Bastos, Félix Carvalho
Amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric, emphathogenic, entactogenic, and hallucinogenic properties. Although most amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine ("ecstasy") represent well-recognized examples, the use of natural related compounds, namely cathinone and ephedrine, has been part of the history of humankind for thousands of years. Resulting from their amphiphilic nature, these drugs can easily cross the blood-brain barrier and elicit their well-known psychotropic effects...
October 2015: Archives of Toxicology
Matthias Liechti
Novel psychoactive substances are newly used designer drugs ("internet drugs", "research chemicals", "legal highs") potentially posing similar health risks to classic illicit substances. Chemically, many novel psychoactive substances can be classified as phenethylamines, amphetamines, synthetic cathinones, piperazines, pipradrols/piperidines, aminoindanes benzofurans, and tryptamines. Pharmacologically, these substances interact with various monoaminergic targets. Typically, stimulants inhibit the transport of dopamine and noradrenaline (pipradrols, pyrovalerone cathinones) or induce the release of these monoamines (amphetamines and methamphetamine-like cathinones), entactogens predominantly enhance serotonin release (phenylpiperazines, aminoindanes, para-substituted amphetamines, and MDMA-like cathinones) similar to MDMA (ecstasy), and hallucinogens (tryptamines, hallucinogenic phenethylamines) are direct agonists at serotonergic 5-HT2A receptors...
2015: Swiss Medical Weekly
Jessica Welter, Pierce Kavanagh, Markus R Meyer, Hans H Maurer
5-APB (5-(2-aminopropyl)benzofuran) and its N-methyl derivative 5-MAPB (N-methyl-5-(2-aminopropyl)benzofuran) are analogues of amphetamine and methamphetamine, respectively, and belong to the so-called novel psychoactive substances (NPS). They were consumed as stimulants or entactogens with euphoric and empathogenic effects. Being controlled in some countries, both compounds should be covered by drug testing in clinical and forensic toxicology. Therefore, metabolism studies have been performed by working up rat urine samples after a high single dose of the corresponding NPS with solid-phase extraction without and after enzymatic conjugates cleavage...
February 2015: Analytical and Bioanalytical Chemistry
Konstantin Kuteykin-Teplyakov, Rafael Maldonado
Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that N-Methyl-3,4-methylenedioxyamphetamine (MDMA, "Ecstasy") at low dose (3mg/kg) has differential effects on mouse social behavior. In some animals, MDMA promotes sociability without hyperlocomotion, whereas in other mice it elevates locomotor activity without affecting sociability...
November 2014: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Andrew C Parrott
MDMA has properties that may make it attractive for psychotherapy, although many of its effects are potentially problematic. These contrasting effects will be critically reviewed in order to assess whether MDMA could be safe for clinical usage. Early studies from the 1980s noted that MDMA was an entactogen, engendering feelings of love and warmth. However, negative experiences can also occur with MDMA since it is not selective in the thoughts or emotions it releases. This unpredictability in the psychological material released is similar to another serotonergic drug, LSD...
January 2014: Journal of Psychoactive Drugs
P Sáez-Briones, A Hernández
Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, "Ecstasy") is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an "open mind state", may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure...
September 2013: Current Neuropharmacology
Péter Pázmány, Péter Petschner, Csaba Ádori, Eszter Kirilly, Dénes Rómeó Andó, Brigitta Balogh, Norbert Gyöngyösi, György Bagdy
The recreational drug ecstasy is widely used among dance clubbers for its acute euphoric and entactogenic effects. Ecstasy exerts its acute effects by increasing the extracellular concentration of monoamines in the brain by reversing the functions of reuptake mechanisms. These elevations in extracellular monoamine concentrations result in wake promoting effects, body hyperthermia and reductions in local cerebral blood flow. However, on the long-run, ecstasy reduces serotonin concentration and density of serotonergic markers in several brain areas...
December 2013: Neuropsychopharmacologia Hungarica
Rebecca L Hartman, Nathalie A Desrosiers, Allan J Barnes, Keming Yun, Karl B Scheidweiler, Erin A Kolbrich-Spargo, David A Gorelick, Robert S Goodwin, Marilyn A Huestis
3,4-Methylenedioxymethamphetamine (MDMA) is an illicit phenethylamine ingested for entactogenic and euphoric effects. Although blood is more commonly submitted for forensic analysis, previous human MDMA pharmacokinetics research focused on plasma data; no direct blood-plasma comparisons were drawn. Blood and plasma specimens from 50 healthy adult volunteers (33 males, 17 females, 36 African-American) who ingested recreational 1.0 and 1.6 mg/kg MDMA doses were quantified for MDMA and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) by two-dimensional gas chromatography-mass spectrometry...
January 2014: Analytical and Bioanalytical Chemistry
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