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Karolina Pekala, Agnieszka Michalak, Marta Kruk-Slomka, Barbara Budzynska, Grazyna Biala
Taking into account the rather frequent concomitance of nicotine abuse and stress, we aimed to research memory- and depression-related effects of nicotine administration in combination with chronic mild unpredictable stress (CMUS) in mice and an involvement of the endocannabinoid system through CB1 and CB2 receptors. Mice were submitted to the CMUS for 4 weeks. Effects on depression-like behaviors and cognition, exerted by a combined administration of CB1, i.e., Oleamide (2.5, 5.0 mg/kg), AM 251 (0.1, 0.25 mg/kg) and CB2, i...
March 15, 2018: Behavioural Brain 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
Amy L Patton, Kathryn A Seely, Azure L Yarbrough, William Fantegrossi, Laura P James, Keith R McCain, Ryoichi Fujiwara, Paul L Prather, Jeffery H Moran, Anna Radominska-Pandya
Synthetic cannabinoids (SCBs), synonymous with 'K2', 'Spice' or 'synthetic marijuana', are psychoactive drugs of abuse that frequently result in clinical effects and toxicity more severe than those classically associated with Δ9 -tetrahydrocannabinol such as extreme agitation, hallucinations, supraventricular tachycardia, syncope, and seizures. JWH-018 is one of the earliest compounds identified in various SCB products, and our laboratory previously demonstrated that JWH-018 undergoes extensive metabolism by cytochromes P450 (P450), binds to, and activates cannabinoid receptors (CBRs)...
March 6, 2018: Biochemical and Biophysical Research Communications
Nadine Schaefer, Ann-Katrin Kroll, Matthias W Laschke, Michael D Menger, Hans H Maurer, Markus R Meyer, Peter H Schmidt
BACKGROUND: Since their appearance on the drugs of abuse market, synthetic cannabinoids (SCs) are gaining increasing toxicological relevance. They are consumed without knowledge of their toxicokinetic (TK) and toxicodynamic properties and human studies are not allowed due to ethical reasons. A controlled animal TK study following nebulization of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) to pigs should be helpful for better interpretation of analytical results in cases of misuse or poisoning...
February 14, 2018: Current Drug Delivery
Willard J Costain, Ingrid Rasquinha, Tanya Comas, Melissa Hewitt, Amy Aylsworth, Yanouchka Rouleau, Vincent Marleau, Evelyn C Soo, Joseph S Tauskela
Synthetic cannabinoids are marketed as legal alternatives to Δ9-THC, and are a growing worldwide concern as these drugs are associated with severe adverse effects. Unfortunately, insufficient information regarding the physiological and pharmacological effects of emerging synthetic cannabinoids (ESCs) makes their regulation by government authorities difficult. One strategy used to evade regulation is to distribute isomers of regulated synthetic cannabinoids. This study characterized the pharmacological properties of a panel of ESCs in comparison to Δ9-THC, as well as six JWH-122 isomers relative to its parent compound (JWH-122-4)...
February 2, 2018: European Journal of Pharmacology
Lucie Fojtíková, Anna Šuláková, Martina Blažková, Barbora Holubová, Martin Kuchař, Petra Mikšátková, Oldřich Lapčík, Ladislav Fukal
In recent years, the use of synthetic cannabinoids (SCs) as drugs of abuse has greatly increased. SCs are associated with a risk of severe poisoning or even death. Therefore, more rapid, cost effective and reliable methods are needed, especially for the screening of drivers after traffic accidents and for detailed toxicological analysis in forensic laboratories. In this study, we developed a lateral flow immunoassay (LFIA) and an enzyme linked immunosorbent assay (ELISA) for the detection of JWH-200 in oral fluids...
2018: Toxicology Reports
Stefan W Toennes, Anna Geraths, Werner Pogoda, Alexander Paulke, Cora Wunder, Eef L Theunissen, Johannes G Ramaekers
Each year, synthetic cannabinoids are occurring in high numbers on the illicit drug market but data obtained after controlled application are rare. The present study on pharmacokinetics in urine is part of a pilot study on adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Six subjects inhaled smoke from 2 and 3mg JWH-018. The drug and ten potential metabolites were analyzed in urine samples collected during 12h after inhalation by liquid chromatography-mass spectrometry (LC-MS/MS) without and with conjugate cleavage...
December 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
Anthea B Mahesan Paul, Lary Simms, Saeideh Amini, Abraham Ebenezer Paul
Synthetic cannabinoids (SCs) are commonly abused by adolescents with reported past year (2013) use in high school students between 3 and 10%. Standard adolescent postmortem toxicology does not include routine SC analysis, and thus, the true burden of fatalities related to SCs is unknown. A retrospective case review of two cases included scene investigation, interviews, autopsy, and toxicology. SCs were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Review of the eight adolescent SC-associated fatalities in the literature revealed five of eight cases had no other discernible cause of death on autopsy...
December 1, 2017: Journal of Forensic Sciences
M Hytti, S Andjelic, N Josifovska, N Piippo, E Korhonen, M Hawlina, K Kaarniranta, T J Nevalainen, G Petrovski, T Parkkari, A Kauppinen
A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB2 ). Here, we have analysed the effect of CB2 activation on cellular survival and inflammation in human RPE cells...
November 23, 2017: Scientific Reports
Eef L Theunissen, Nadia R P W Hutten, Natasha L Mason, Stefan W Toennes, Kim P C Kuypers, Eliza B de Sousa Fernandes Perna, Johannes G Ramaekers
BACKGROUND AND PURPOSE: Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to their easy access and portrayed safety. Controlled studies on the behavioural effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds. EXPERIMENTAL APPROACH: This is a first attempt to assess the influence of a synthetic cannabinoid, JWH-018, on neurocognition and subjective experience in humans after controlled administration...
January 2018: British Journal of Pharmacology
Ziva D Cooper, Justin L Poklis, Fei Liu
Synthetic cannabinoids (SCs) are a significant public health concern given their widespread use and severe effects associated with intoxication. However, there is a paucity of controlled human studies investigating the behavioral and physiological effects and pharmacokinetics of these compounds. Designing a reliable method to administer consistent, concentration-dependent synthetic cannabinoids is an integral component of controlled study of these compounds. Further, optimizing methods to assess the parent compounds and metabolites in plasma is critical in order to be able to establish their pharmacokinetics after administration...
November 14, 2017: Neuropharmacology
Christina McDonnell, Sergi Leánez, Olga Pol
The activation of the transcription factor Nrf2 inhibits neuropathy and modulates the activity of delta-opioid receptors (DOR) in type 2 diabetic mice but the impact of Nrf2/HO-1 pathway on the antinociceptive actions of cannabinoid 2 receptors (CB2R) has not been assessed. Using male mice BKS.Cg-m+/+Leprdb/J (db/db) we investigated if treatment with cobalt protoporphyrin IX (CoPP), an HO-1 inductor, inhibited mechanical allodynia, hyperglycemia and obesity associated to type 2 diabetes. The antinociceptive effects of JWH-015 and JWH-133 (CB2R agonists) administered with and without CoPP or sulforaphane (SFN), a Nrf2 transcription factor activator, have been also evaluated...
October 28, 2017: International Journal of Molecular Sciences
Evelyn López-Dyck, Felipa Andrade-Urzúa, Alejandro Elizalde, Tania Ferrer-Villada, Adan Dagnino-Acosta, Miguel Huerta, Zyanya Osuna-Calleros, Cinthia Rangel-Sandoval, Enrique Sánchez-Pastor
BACKGROUND: Some cannabinoids, a family of compounds derived from Cannabis sativa (marijuana), have previously shown vasodilator effects in several studies, a feature that makes them suitable for the generation of a potential treatment for hypertension. The mechanism underlying this vasodilator effect in arteries is still controversial. In this report, we explored how the synthetic cannabinoids ACPA (CB1 -selective agonist) and JWH-133 (CB2 -selective agonist) regulate the vascular tone of rat superior mesenteric arteries...
December 2017: Pharmacological Reports: PR
Julie A Marusich, Jenny L Wiley, Timothy W Lefever, Purvi R Patel, Brian F Thomas
Diversion of synthetic cannabinoids from the lab to drugs of abuse has become increasingly prevalent in recent years. Moreover, as earlier synthetic cannabinoids were banned, manufacturers introduced a new supply of novel compounds to serve as replacements. Hence, the chemical diversity of synthetic cannabinoid analogs has also rapidly increased. The present study examined 8 new synthetic cannabinoids: AM-1220, AM-2232, AM-2233, AM-679, EAM-2201, JWH-210, JHW-251, and MAM-2201. Each compound was assessed for binding affinity and functional activation of CB1 and CB2 receptors, and pharmacological equivalence with Δ(9)-tetrahydrocannabinol (THC) in THC drug discrimination...
November 4, 2017: Neuropharmacology
Laura Hondebrink, Anne Zwartsen, Remco H S Westerink
The use of new psychoactive substances (NPS) is increasing and currently >600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP)...
February 2018: Pharmacology & Therapeutics
Maren Hermanns-Clausen, Dieter Müller, Josephine Kithinji, Verena Angerer, Florian Franz, Florian Eyer, Hartmud Neurath, Gesine Liebetrau, Volker Auwärter
INTRODUCTION: In 2014, the "European Monitoring Centre for Drugs and Drug Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among these were indole- and indazole-based valine derivatives with a cyclohexylmethyl side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of SCs. METHODS: A prospective observational study of patients treated in emergency departments (EDs) after the intake of SCs was conducted. Clinical and laboratory data were combined and reported to a poison control centre...
October 26, 2017: Clinical Toxicology
Ersin Göl, İsmet Çok
Synthetic cannabinoids mimic the effects of cannabis and are the largest and fastest growing class of newly appearing designer drugs. Reports have revealed that various types of synthetic cannabinoids are mixed with herbal substances. The present study investigated the herbal substance cases involving synthetic cannabinoids in Ankara and nearby cities in Turkey. Data were collected from the reports of synthetic cannabinoids that were analyzed between January 01, 2011 and December 31, 2015 in the Ankara Narcotic Department of the Council of Forensic Medicine at the request of the judicial authorities...
November 2017: Forensic Science International
Stefan W Toennes, Anna Geraths, Werner Pogoda, Alexander Paulke, Cora Wunder, Eef L Theunissen, Johannes G Ramaekers
BACKGROUND: Each year, synthetic cannabinoids are occurring in high numbers on the illicit drug market, but data on their detectability are rarely available. Therefore, a pilot study was performed to assess adverse effects of JWH-018, which is one of the oldest and best known synthetic cannabinoids. Oral fluid has been evaluated as a specimen for drug monitoring. METHODS: Six subjects inhaled smoke derived from 2 and 3 mg JWH-018. The drug and ten of its metabolites were analyzed in oral fluid samples collected during the following 12 hours using the Quantisal collection device by liquid chromatography-mass spectrometry (LC-MS/MS)...
October 2, 2017: Drug Testing and Analysis
Nico Langer, Franziska Steinicke, Rainer Lindigkeit, Ludger Ernst, Till Beuerle
One of the main reasons for the rise in popularity of synthetic cannabinoids (SCs) is their ability to remain unrecognized in conventional drug screenings. Due to their structural diversity, caused by the constant introduction of new substances to circumvent legal regulation, antibodies with a wide range of cross-reactivity are necessary for the establishment of a reliable immunological based drug test. Therefore, high-quality binding data are needed to select promising antibody candidates for further development...
September 18, 2017: Forensic Science International
Francesca Punzo, Chiara Tortora, Daniela Di Pinto, Iolanda Manzo, Giulia Bellini, Fiorina Casale, Francesca Rossi
Osteosarcoma is the most common and aggressive bone tumor in children. The Endocannabinoid/Endovanilloid system has been proposed as anticancer target in tumor of different origins. This system is composed of two receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and their ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells. We investigated the effects of JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) in six human Osteosarcoma cell lines: MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu, by Apoptosis and Migration-Assay...
August 15, 2017: Oncotarget
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