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Synthetic cannabinoids

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https://www.readbyqxmd.com/read/28730896/cannabinoid-hyperemesis-syndrome-potential-mechanisms-for-the-benefit-of-capsaicin-and-hot-water-hydrotherapy-in-treatment
#1
John R Richards, Jeff M Lapoint, Guillermo Burillo-Putze
INTRODUCTION: Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. OBJECTIVES: In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation...
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28716633/the-synthetic-cannabinoid-win55212-2-ameliorates-traumatic-spinal-cord-injury-via-inhibition-of-gapdh-siah1-in-a-cb2-receptor-dependent-manner
#2
Bin-Xiao Su, Xin Chen, Jia Huo, Shu-Yun Guo, Rui Ma, Yan-Wu Liu
The essential role of GAPDH/Siah1 signaling pathway in the pathogenesis of various injurious conditions such as traumatic spinal cord injury (SCI) has been gradually recognized. However, the drugs targeting this signaling pathway are still lacking. The endocannabinoid system, including its receptors (CB1 and CB2), act as neuroprotective and immunomodulatory modulators in SCI. WIN55212-2, an agonist for CB1 and CB2 receptors, has been demonstrated with anti-inflammatory and anti-apoptotic effects in multiple neurological diseases...
July 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28713291/an-expanding-world-of-novel-psychoactive-substances-opioids
#3
REVIEW
Jolanta B Zawilska
The abuse of novel psychoactive substances (NPS) has been increasing dramatically worldwide since late 2000s. By the end of 2015, more than 560 NPS had been reported to the European Monitoring Centre for Drugs and Drug Addiction. Although the most popular compounds are synthetic cannabinoids and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel synthetic opioids have recently emerged on the recreational drug market. They include fentanyl (a potent narcotic analgesic) and its analogs (e...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28707493/ab-chminaca-induced-sudden-death-from-non-cardiogenic-pulmonary-edema
#4
Hideyuki Maeda, Ruri Kikura-Hanajiri, Maiko Kawamura, Erika Nagashima, Ken-Ichi Yoshida
CONTEXT: Despite widespread use of diverse synthetic cannabinoid (sCB) compounds, the pathophysiology associated with intoxication with many sCB compounds, including AB-CHMINACA, is poorly understood, as is their metabolism and distribution into blood and organs. CASE DETAILS: A young man died shortly after ingesting an herb product containing sCB compounds. Toxicological analyses of blood samples revealed high levels of AB-CHMINACA (7.61 ± 0.59 ng/mL) and its metabolites (M2, 56...
July 14, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28706566/motor-vehicle-collisions-caused-by-the-super-strength-synthetic-cannabinoids-mam-2201-5f-pb-22-5f-ab-pinaca-5f-amb-and-5f-adb-in-japan-experienced-from-2012-to-2014
#5
REVIEW
Shuji Kaneko
From 2012 to 2014 in Japan, 214 cases of motor vehicle collisions were attributed to the use of illegal drugs. In 93 out of 96 investigated cases, the causative agents were a variety of synthetic cannabinoids (SCs). These SCs can be classified into three groups according to the lineage of the chemical structures: (1) naphthoyl indoles, such as MAM-2201, (2) quinolinyl ester indoles, such as 5F-PB-22, and (3) indazole carboxamides, such as 5F-AB-PINACA, 5F-AMB, and 5F-ADB. These SCs became available sequentially with increasing cannabinoid CB1 agonist potencies and reached a nationwide outbreak in the summer of 2014...
2017: Forensic Toxicology
https://www.readbyqxmd.com/read/28700290/lower-risk-cannabis-use-guidelines-a-comprehensive-update-of-evidence-and-recommendations
#6
Benedikt Fischer, Cayley Russell, Pamela Sabioni, Wim van den Brink, Bernard Le Foll, Wayne Hall, Jürgen Rehm, Robin Room
BACKGROUND: Cannabis use is common in North America, especially among young people, and is associated with a risk of various acute and chronic adverse health outcomes. Cannabis control regimes are evolving, for example toward a national legalization policy in Canada, with the aim to improve public health, and thus require evidence-based interventions. As cannabis-related health outcomes may be influenced by behaviors that are modifiable by the user, evidence-based Lower-Risk Cannabis Use Guidelines (LRCUG)-akin to similar guidelines in other health fields-offer a valuable, targeted prevention tool to improve public health outcomes...
August 2017: American Journal of Public Health
https://www.readbyqxmd.com/read/28694184/engineering-yeasts-as-platform-organisms-for-cannabinoid-biosynthesis
#7
Bastian Zirpel, Friederike Degenhardt, Chantale Martin, Oliver Kayser, Felix Stehle
Δ(9)-tetrahydrocannabinolic acid (THCA) is a plant derived secondary natural product from the plant Cannabis sativa l. The discovery of the human endocannabinoid system in the late 1980s resulted in a growing number of known physiological functions of both synthetic and plant derived cannabinoids. Thus, manifold therapeutic indications of cannabinoids currently comprise a significant area of research. Here we reconstituted the final biosynthetic cannabinoid pathway in yeasts. The use of the soluble prenyltransferase NphB from Streptomyces sp...
July 7, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28692429/synthetic-cannabinoids-the-hidden-side-of-spice-drugs
#8
Nicholas Pintori, Barbara Loi, Maddalena Mereu
Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to mimic the psychoactive ingredient in marijuana [Δ-tetrahydrocannabinol (Δ-THC)] and synthesized by introducing modifications to the chemical structure of parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid use/abuse can be devastating as toxicological effects and adverse reactions cannot be entirely predicted and may vary with the dose, route of administration, individual vulnerability and concomitant intake with other drugs...
July 7, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28692400/developing-syndromic-surveillance-to-monitor-and-respond-to-adverse-health-events-related-to-psychoactive-substance-use-methods-and-applications
#9
Michelle L Nolan, Hillary V Kunins, Ramona Lall, Denise Paone
INTRODUCTION: Recent increases in drug overdose deaths, both in New York City and nationally, highlight the need for timely data on psychoactive drug-related morbidity. We developed drug syndrome definitions for syndromic surveillance to monitor drug-related emergency department (ED) visits in real time. MATERIALS AND METHODS: We used 2012 archived syndromic surveillance data from New York City hospitals to develop definitions for psychoactive drug-related syndromes...
July 2017: Public Health Reports
https://www.readbyqxmd.com/read/28692384/advancing-the-use-of-emergency-department-syndromic-surveillance-data-new-york-city-2012-2016
#10
Ramona Lall, Jasmine Abdelnabi, Stephanie Ngai, Hilary B Parton, Kelly Saunders, Jessica Sell, Amanda Wahnich, Don Weiss, Robert W Mathes
INTRODUCTION: The use of syndromic surveillance has expanded from its initial purpose of bioterrorism detection. We present 6 use cases from New York City that demonstrate the value of syndromic surveillance for public health response and decision making across a broad range of health outcomes: synthetic cannabinoid drug use, heat-related illness, suspected meningococcal disease, medical needs after severe weather, asthma exacerbation after a building collapse, and Ebola-like illness in travelers returning from West Africa...
July 2017: Public Health Reports
https://www.readbyqxmd.com/read/28691766/detection-of-metabolites-of-the-new-synthetic-cannabinoid-cumyl-4cn-binaca-in-authentic-urine-samples-and-human-liver-microsomes-using-high-resolution-mass-spectrometry
#11
Yeter Erol Ozturk, Oya Yeter, Serkan Ozturk, Goksun Karakus, Ismail Ates, Yalçın Buyuk, Turkan Yurdun
CUMYL-4CN-BINACA(1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide) is a recently introduced indazole-3-carboxamide type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine Istanbul Narcotics Department in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL-4CN-BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n=80)...
July 10, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28688175/discrimination-between-closely-related-synthetic-cannabinoids-by-gc-cold-ei-ms
#12
Evgeny Smolianitski-Fabian, Etia Cohen, Marina Dronova, Anna Voloshenko-Rossin, Ovadia Lev
Gas chromatography thermal-electron ionization mass spectrometry (GC-EI-MS) is an established method for the identification of mind-altering substances and is routinely used by forensic laboratories. However, some commonly analyzed drugs of abuse, relating to the synthetic cannabinoids receptor agonist group (SCs), pose a challenge for this conventional technique. As the molecular cation radicals of many excited SCs are labile within the ion source, the relative abundance of the molecular ions obtained by the GC-EI-MS is often too small to allow discrimination of structurally related drugs...
July 8, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28686542/polyunsaturated-fatty-acids-and-endocannabinoids-in-health-and-disease
#13
Hércules Rezende Freitas, Alinny Rosendo Isaac, Renato Malcher-Lopes, Bruno Lourenço Diaz, Isis Hara Trevenzoli, Ricardo Augusto De Melo Reis
Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field...
July 7, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28685136/bilateral-renal-cortical-necrosis-associated-with-smoking-synthetic-cannabinoids
#14
Kanaan Mansoor, Ashley Zawodniak, Tibor Nadasdy, Zeid J Khitan
Synthetic cannabinoids have become a common drug of abuse in recent years and their toxicities have come to light as well. They are known to be notorious for the kidneys, with acute tubular necrosis, acute interstitial nephritis and rhabdomyolysis induced renal injury being the frequent nephrotoxic outcomes in users. We report a case of bilateral renal cortical necrosis, leading to irreversible renal damage and lifelong dialysis dependency.
June 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28678776/crystal-structures-of-agonist-bound-human-cannabinoid-receptor-cb1
#15
Tian Hua, Kiran Vemuri, Spyros P Nikas, Robert B Laprairie, Yiran Wu, Lu Qu, Mengchen Pu, Anisha Korde, Shan Jiang, Jo-Hao Ho, Gye Won Han, Kang Ding, Xuanxuan Li, Haiguang Liu, Michael A Hanson, Suwen Zhao, Laura M Bohn, Alexandros Makriyannis, Raymond C Stevens, Zhi-Jie Liu
The cannabinoid receptor 1 (CB1) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Here we report two agonist-bound crystal structures of human CB1 in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 Å and 2.95 Å resolution, respectively. The two CB1-agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28677397/c1-azacycloalkyl-hexahydrocannabinols
#16
Thanh C Ho, Naoyuki Shimada, Marcus A Tius, Spyros P Nikas, Wen Zhang, Alexandros Makriyannis
We report the design, synthesis, and biological evaluation of a novel class of cannabinergic ligands namely C1'-azacycloalkyl hexahydrocannabinols. Our synthetic approaches utilize an advanced common chiral intermediate triflate from which all analogs could be derived. Key synthetic steps involve microwave assisted Liebeskind-Srogl C-C cross-coupling and palladium-catalyzed decarboxylative coupling reactions. The C1'-N-methyl-azetidinyl- and C1'-N-methyl-pyrrolidinyl-analogs were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors...
July 5, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28673548/inhibition-of-the-endocannabinoid-regulating-enzyme-monoacylglycerol-lipase-elicits-a-cb1-receptor-mediated-discriminative-stimulus-in-mice
#17
Robert A Owens, Mohammed A Mustafa, Bogna M Ignatowska-Jankowska, M Imad Damaj, Patrick M Beardsley, Jenny L Wiley, Micah J Niphakis, Benjamin F Cravatt, Aron H Lichtman
Substantial challenges exist for investigating the cannabinoid receptor type 1 (CB1)-mediated discriminative stimulus effects of the endocannabinoids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide; AEA), compared with exogenous CB1 receptor agonists, such as Δ(9)-tetrahydrocannabinol (THC) and the synthetic cannabinoid CP55,940. Specifically, each is rapidly degraded by the respective hydrolytic enzymes, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH). Whereas MAGL inhibitors partially substitute for THC and fully substitute for CP55,940, FAAH inhibitors do not substitute for either drug...
June 30, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28670781/structural-characterization-and-pharmacological-evaluation-of-the-new-synthetic-cannabinoid-cumyl-pegaclone
#18
Verena Angerer, Lukas Mogler, Jan-Patrick Steitz, Philippe Bisel, Cornelius Hess, Clara T Schoeder, Christa E Müller, Laura M Huppertz, Folker Westphal, Jan Schäper, Volker Auwärter
The number of new psychoactive substances (NPS) that have emerged on the European market has been rapidly growing in the last years, with a particularly high number of new compounds from the group of synthetic cannabinoid receptor agonists. There have been various political efforts to control the trade and the use of NPS worldwide. In Germany, the 'Act to control the distribution of new psychoactive substances' (NpSG) came into force in November 2016. In this new Act two groups of substances were defined, the group 'cannabimimetics/synthetic cannabinoids' covering indole, indazole and benzimidazole core structures, and a second group named 'compounds derived from 2-phenethylamine'...
July 3, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28668480/a-new-challenge-in-forensic-toxicology-exemplified-by-a-case-of-murder-under-the-influence-of-a-synthetic-cannabinoid-am-2201
#19
Sebastian Rojek, Małgorzata Kłys, Martyna Maciów-Głąb, Karol Kula
Among new psychoactive substances (NPS) available on the narcotic market, a significant number consists of synthetic cannabinoids commonly known as smokable herbal "spice" and "K2", and which are legally treated as a legal alternative to marijuana. The dearth of information on the pharmacology of these intoxicants as they are introduced into the market has created the urgent need among healthcare providers for case studies on the substances belonging to this group, both in terms of the consequences of using such intoxicants, and in methods of detection...
June 24, 2017: Legal Medicine
https://www.readbyqxmd.com/read/28655644/pregnenolone-does-not-interfere-with-the-effects-of-cannabinoids-on-synaptic-transmission-in-the-cerebellum-and-the-nucleus-accumbens
#20
Anna Krohmer, Martin Brehm, Volker Auwärter, Bela Szabo
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ(9)-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication. The primary neuronal cannabinoid action behind most of the behavioural and somatic effects of cannabinoids is presynaptic inhibition of synaptic transmission. Therefore, the hypothesis of the present study was that pregnenolone attenuates the inhibition of synaptic transmission elicited by cannabinoids...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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