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Danielle Gulick, Joshua J Gamsby
Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great progress has been made in that short time toward understanding how drugs of abuse impact the molecular and physiological circadian clocks, as well as how disruption of normal circadian rhythm biology may contribute to addiction and ameliorate the efficacy of treatments for addiction...
March 15, 2018: Pharmacology & Therapeutics
Marie Mardal, Petur Weihe Dalsgaard, Bing Qi, Christian Brinch Mollerup, Pieter Annaert, Kristian Linnet
The main analytical targets of synthetic cannabinoids are often metabolites. With the high number of new psychoactive substances entering the market, suitable workflows are needed for analytical target identification in biological samples. The aims of this study were to identify the main metabolites of the synthetic cannabinoids, AMB-CHMICA and 5C-AKB48, using an in silico-assisted workflow with analytical data acquired using ultra-high-performance liquid chromatography-(ion mobility spectroscopy)-high resolution-mass spectrometry in data-independent acquisition mode (UHPLC-(IMS)-HR-MSE )...
March 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Irving Zucker
Breastfeeding women are excluded from clinical trials of psychoactive drugs because of ethical concerns. Animal testing, which often is predictive of adverse effects in humans, represents the only avenue available for assessing drug safety for human offspring exposed to drugs during lactation. I determined whether behavioral outcomes for children exposed during breastfeeding to antidepressants, anxiolytics, antipsychotics, anti-seizure medications, analgesics, sedatives, and marijuana can be predicted by rodent studies of offspring exposed to drugs during lactation...
March 16, 2018: Psychopharmacology
Thomas F Gamage, Charlotte E Farquhar, Timothy W Lefever, Julie A Marusich, Richard C Kevin, Iain S McGregor, Jenny L Wiley, Brian F Thomas
Synthetic cannabinoids are a class of novel psychoactive substances that exhibit high affinity at the cannabinoid type-1 (CB1) receptor and produce effects similar to those of THC, the primary psychoactive constituent of cannabis. Illicit drug manufacturers are continually circumventing laws banning the sale of synthetic cannabinoids by synthesizing novel structures and doing so with little regard for their potential impact on pharmacological and toxicological effects. Synthetic cannabinoids produce a wide range of effects including cardiotoxicity, seizure activity, and kidney damage and can result in death...
March 16, 2018: Journal of Pharmacology and Experimental Therapeutics
Samuel Mesihää, Ilpo Rasanen, Ilkka Ojanperä
Gas chromatography (GC) hyphenated with nitrogen chemiluminescence detection (NCD) and quadrupole time-of-flight mass spectrometry (QTOFMS) was applied for the first time to the quantitative analysis of new psychoactive substances (NPS) in urine, based on the N-equimolar response of NCD. A method was developed and validated to estimate the concentrations of three metabolites of the common stimulant NPS α-pyrrolidinovalerophenone (α-PVP) in spiked urine samples, simulating an analysis having no authentic reference standards for the metabolites and using the parent drug instead for quantitative calibration...
February 27, 2018: Forensic Science International
Elle Wadsworth, Colin Drummond, Paolo Deluca
The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets and considers whether crypto markets are a reliable platform for the sale of NPS. Data was collected from 22 crypto markets that were accessed through the hidden web using the Onion Router (Tor). Data collection took place bimonthly from October 2015 to October 2016 as part of the CASSANDRA ( C omputer A ssisted S olutions for S tudying the A vailability a N d D ist R ibution of novel psycho A ctive substances) project...
March 16, 2018: Brain Sciences
Michael J Zvolensky, Andrew H Rogers, Kara Manning, Julianna B D Hogan, Daniel J Paulus, Julia D Buckner, Nubia A Mayorga, Gerald Hallford, Norman B Schmidt
Cannabis is among the most widely used psychoactive substances in the United States, and rates of cannabis use and cannabis-related problems are increasing. Anxiety sensitivity, or the fear of aversive interoceptive sensations, may be relevant to better understanding cannabis use problems and other significant cannabis use processes (e.g., beliefs about quitting). Previous research has primarily focused on the global anxiety sensitivity construct; however, anxiety sensitivity lower-order facets (Cognitive Concerns, Physical Concerns, and Social Concerns) tend to be differentially related to substance use processes in non-cannabis specific studies...
March 5, 2018: Psychiatry Research
Igam Bagra, Vijay Krishnan, Ravindra Rao, Alok Agrawal
OBJECTIVES: Use of various psychoactive substances can influence outcomes of patients on opioid agonist treatment (OAT). While use of alcohol and cocaine has shown to adversely affect OAT results, associated cannabis use shows mixed results. This study aimed to assess the pattern of cannabis use among opioid-dependent patients maintained on buprenorphine. Additionally, the study compared the dose of buprenorphine, opioid-related craving and withdrawals, productivity, and also quality of life between those with and without recent (past 90-day) cannabis use...
March 14, 2018: Journal of Addiction Medicine
Sebastian V Nielsen, Martin Kellner, Per G Henriksen, Håkan Olsén, Steen H Hansen, Erik Baatrup
Selective serotonin re-uptake inhibitors are pharmaceuticals used to treat a range of psychological disorders. They are frequently found in surface waters in populated areas. In recent years, they have been shown to affect the behaviour of various aquatic organisms in a way that can have ecological effects. In this study, we exposed zebrafish of both sexes to nominally 0.00, 0.15 and 1.50 µg L-1 Escitalopram in flow-through tanks for three weeks. Subsequently, ten swimming behaviour parameters were quantified using high-resolution video tracking...
March 14, 2018: Ecotoxicology
Leandro Nóbrega, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U...
March 14, 2018: Drug Metabolism Reviews
Philippe A Melas, Johanna S Qvist, Matteo Deidda, Chirag Upreti, Ya Bin Wei, Fabrizio Sanna, Walter Fratta, Maria Scherma, Paola Fadda, Denise B Kandel, Eric R Kandel
Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus...
March 13, 2018: Cell Reports
Xiaochen Wang, Zhendong Hua, Zhaoguang Yang, Haipu Li, Huwei Liu, Bo Qiu, Honggang Nie
RATIONALE: Owing to the widespread abuse of new psychoactive substances (NPSs), developing a rapid, easily operable method to detect NPSs in oral fluid is of high priority. Easy collection and non-invasive nature make oral fluid samples suitable for on-site tests and forensic cases. Herein we report a rapid and sensitive method to screen and quantitate 11 new NPSs in oral fluid. METHOD: A low temperature plasma probe mass spectrometry (LTP-MS) was applied and to improve the signal intensity, thermally assisted desorption was employed...
March 14, 2018: Rapid Communications in Mass Spectrometry: RCM
Juan Andrés Abin-Carriquiry, Marcela Martínez-Busi, Martín Galvalisi, Manuel Minteguiaga, José Pedro Prieto, María Cecilia Scorza
Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce. Besides, it is unknown if adulterants remain stable when CP is heated. This study was designed to report the chemical content of an extensive series of CP seized samples and to demonstrate the stability (i...
March 13, 2018: Neurotoxicity Research
Joshua S Elmore, Michael H Baumann
Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) is a synthetic compound found in psychoactive "spice" products that activates cannabinoid receptors. Preclinical evidence suggests that exposure to synthetic cannabinoids increases 5-HT2A/2C receptor function in the brain, an effect which might contribute to psychotic symptoms. Here, we hypothesized that repeated exposures to JWH-018 would enhance behavioral responsiveness to the 5-HT2A/2C receptor agonist DOI. Male Sprague-Dawley rats fitted with subcutaneously (sc) temperature transponders received daily injections of JWH-018 (1...
2018: Frontiers in Psychiatry
Loretta Theresa Ford, Jonathan David Berg
Novel psychotropic substances (NPS) also known as legal highs are a major concern in UK prisons, fuelling violence and putting a strain on resources for inmates requiring medical treatment for adverse effects. We provide a clinical toxicology service including routine screening for NPS. In 2015 we were approached by Her Majesty Prison Service (HMPS) search dog training team to advise on which NPS to target, and again in 2016 to further provide analytical support to test five letters which the dogs positively identified for NPS during routine searches of prison mail rooms...
January 1, 2018: Annals of Clinical Biochemistry
Shenglong Zou, Ujendra Kumar
The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites...
March 13, 2018: International Journal of Molecular Sciences
Andrew C Parrott
Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will show how they disrupt the same core psychobiological functions, so damaging well-being in similar ways. Every psychoactive drug causes mood states to fluctuate. Users feel better on-drug, then feel worse off-drug. The strength of these mood fluctuations is closely related to their addiction potential...
March 13, 2018: Brain Sciences
Elliot B Tapper, Neehar D Parikh, Akbar K Waljee, Michael Volk, Noelle E Carlozzi, Anna S-F Lok
OBJECTIVES: Minimal hepatic encephalopathy (HE) is common, characterized by deficits in reaction time and executive function, and strongly associated with disability and mortality. Point-of-care diagnostics performed without specialized skills or equipment are now available, albeit with limited data regarding their generalizability. METHODS: We systematically reviewed MEDLINE, EMBASE, Cochrane Library, and Scopus for diagnostic studies of MHE using broad search terms including HE and minimal, covert, or the names of published diagnostic modalities...
March 13, 2018: American Journal of Gastroenterology
Elon Richman, Nathan J Skoller, Bernice Fokum, Brandi A Burke, Chelsea A Hickerson, Robert O Cotes
: Synthetic cathinones are a class of novel psychoactive substances. α-Pyrrolidinopentiophenone (α-PVP), or "Flakka", is one of these substances. Users often present acutely psychotic or agitated. We present the case of a 20-year-old male without prior psychiatric history who was brought to the hospital by his family because of increasingly bizarre and erratic behavior after reported ingestion of Flakka. What ensued was a prolonged course of psychosis and severe catatonia. Synthetic cathinones are thought to cause catatonia in approximately 1% of cases...
March 12, 2018: Journal of Addiction Medicine
Torben Breindahl, Peter Hindersson, Peter Derek-Christian Leutscher, Andreas Kimergård
The emergence of an increasing number of new psychoactive substances (NPS) on the drug market requires a paradigm shift in drug testing. Immunoassay screening needs to be replaced with highly specific and sensitive analytical methods based on chromatography and mass spectrometry to produce accurate results, promote health and patient safety and collect data on the prevalence of NPS use, impact on public health and clinical aspects of NPS in Denmark. Development and implementation of new analytical methods currently present a major challenge for both clinical and forensic laboratories...
March 12, 2018: Ugeskrift for Laeger
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