Adolescent delta-9-tetrahydrocannabinol (THC) exposure fails to affect THC-induced place and taste conditioning in adult male rats.

Science.gov (United States)

Wakeford, Alison G P; Flax, Shaun M; Pomfrey, Rebecca L; Riley, Anthony L

2016-01-01

Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

A theoretical study for thorium monocarbide (ThC)

Energy Technology Data Exchange (ETDEWEB)

Aydin, S.; Tatar, A. [Gazi University, Department of Physics, Teknikokullar 06500, Ankara (Turkey); Ciftci, Y.O., E-mail: yasemin@gazi.edu.tr [Gazi University, Department of Physics, Teknikokullar 06500, Ankara (Turkey)

2012-10-15

Highlights: Black-Right-Pointing-Pointer We focused on high pressure behavior of ThC. Black-Right-Pointing-Pointer ThC is metallic, and mechanically stable. Black-Right-Pointing-Pointer The obtained results agree with the other available values. Black-Right-Pointing-Pointer ThC is hard material, and hardness increases properly with pressure. - Abstract: The structural, mechanical, electronic and thermodynamic properties of thorium monocarbide (ThC) with NaCl-type structure have been investigated by using first-principles plane wave density functional calculations with GGA, LDA and LDA + U functionals. It is shown that calculated equilibrium structural parameters of ThC are in agreement with the experimental results. It is seen from calculated single-crystal elastic constants that ThC with NaCl-type structure is mechanically stable. And from calculated density of states and band structure, it is observed that ThC is metallic. After the properties at 0 GPa are clarified, pressure dependency of the structural parameters, the elastic properties and related mechanical properties, density of states (DOS) and hardness are studied. Furthermore, the thermodynamic properties of ThC are obtained from the quasi-harmonic Debye model (QHM) over high pressure and temperature ranges for three functionals. The results are compared to each other, and the available experimental and theoretical data.

A theoretical study for thorium monocarbide (ThC)

International Nuclear Information System (INIS)

Aydin, S.; Tatar, A.; Ciftci, Y.O.

2012-01-01

Highlights: ► We focused on high pressure behavior of ThC. ► ThC is metallic, and mechanically stable. ► The obtained results agree with the other available values. ► ThC is hard material, and hardness increases properly with pressure. - Abstract: The structural, mechanical, electronic and thermodynamic properties of thorium monocarbide (ThC) with NaCl-type structure have been investigated by using first-principles plane wave density functional calculations with GGA, LDA and LDA + U functionals. It is shown that calculated equilibrium structural parameters of ThC are in agreement with the experimental results. It is seen from calculated single-crystal elastic constants that ThC with NaCl-type structure is mechanically stable. And from calculated density of states and band structure, it is observed that ThC is metallic. After the properties at 0 GPa are clarified, pressure dependency of the structural parameters, the elastic properties and related mechanical properties, density of states (DOS) and hardness are studied. Furthermore, the thermodynamic properties of ThC are obtained from the quasi-harmonic Debye model (QHM) over high pressure and temperature ranges for three functionals. The results are compared to each other, and the available experimental and theoretical data.

Total Hydrocarbon Content (THC) Testing in Liquid Oxygen (LOX)

Science.gov (United States)

Meneghelli, B. J.; Obregon, R. E.; Ross, H. R.; Hebert, B. J.; Sass, J. P.; Dirschka, G. E.

2016-01-01

The measured Total Hydrocarbon Content (THC) levels in liquid oxygen (LOX) systems at Stennis Space Center (SSC) have shown wide variations. Examples of these variations include the following: 1) differences between vendor-supplied THC values and those obtained using standard SSC analysis procedures; and 2) increasing THC values over time at an active SSC test stand in both storage and run vessels. A detailed analysis of LOX sampling techniques, analytical instrumentation, and sampling procedures will be presented. Additional data obtained on LOX system operations and LOX delivery trailer THC values during the past 12-24 months will also be discussed. Field test results showing THC levels and the distribution of the THC's in the test stand run tank, modified for THC analysis via dip tubes, will be presented.

Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC.

Science.gov (United States)

Lile, Joshua A; Kelly, Thomas H; Hays, Lon R

2014-10-01

Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures. Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam (5 and 10mg), Δ(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Δ(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and elevated heart rate. Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of Δ(9)-THC. These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC, and by extension cannabis, in humans. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Draft Genome Sequence of Lactobacillus casei Lbs2.

Science.gov (United States)

Bhowmick, Swati; Malar, Mathu; Das, Abhishek; Kumar Thakur, Bhupesh; Saha, Piu; Das, Santasabuj; Rashmi, H M; Batish, Virender K; Grover, Sunita; Tripathy, Sucheta

2014-12-24

We report here a 3.2-Mb draft assembled genome of Lactobacillus casei Lbs2. The bacterium shows probiotic and immunomodulatory activities. The genome assembly and annotation will help to identify molecules and pathways responsible for interaction between the host immune system and the microbe. Copyright © 2014 Bhowmick et al.

Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC.

Science.gov (United States)

Lile, Joshua A; Kelly, Thomas H; Hays, Lon R

2011-07-01

Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment. Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected. Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures. These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD.

Science.gov (United States)

2003-01-01

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive

Reasons for Synthetic THC Use among College Students

Science.gov (United States)

Vidourek, Rebecca A.; King, Keith A.; Burbage, Michelle L.

2013-01-01

Synthetic THC, also known as fake marijuana, is used by college students in the United States. The present study examined reasons for recent synthetic THC use among college students (N = 339). Students completed a 3-page survey during regularly scheduled class times. Results indicated students reported using synthetic THC for curiosity, to get…

Drift-Scale Coupled Processes (DST and THC Seepage) Models

International Nuclear Information System (INIS)

Dixon, P.

2004-01-01

The purpose of this Model Report (REV02) is to document the unsaturated zone (UZ) models used to evaluate the potential effects of coupled thermal-hydrological-chemical (THC) processes on UZ flow and transport. This Model Report has been developed in accordance with the ''Technical Work Plan for: Performance Assessment Unsaturated Zone'' (Bechtel SAIC Company, LLC (BSC) 2002 [160819]). The technical work plan (TWP) describes planning information pertaining to the technical scope, content, and management of this Model Report in Section 1.12, Work Package AUZM08, ''Coupled Effects on Flow and Seepage''. The plan for validation of the models documented in this Model Report is given in Attachment I, Model Validation Plans, Section I-3-4, of the TWP. Except for variations in acceptance criteria (Section 4.2), there were no deviations from this TWP. This report was developed in accordance with AP-SIII.10Q, ''Models''. This Model Report documents the THC Seepage Model and the Drift Scale Test (DST) THC Model. The THC Seepage Model is a drift-scale process model for predicting the composition of gas and water that could enter waste emplacement drifts and the effects of mineral alteration on flow in rocks surrounding drifts. The DST THC model is a drift-scale process model relying on the same conceptual model and much of the same input data (i.e., physical, hydrological, thermodynamic, and kinetic) as the THC Seepage Model. The DST THC Model is the primary method for validating the THC Seepage Model. The DST THC Model compares predicted water and gas compositions, as well as mineral alteration patterns, with observed data from the DST. These models provide the framework to evaluate THC coupled processes at the drift scale, predict flow and transport behavior for specified thermal-loading conditions, and predict the evolution of mineral alteration and fluid chemistry around potential waste emplacement drifts. The DST THC Model is used solely for the validation of the THC

How to Reduce Corruption | Collier | LBS Management Review

African Journals Online (AJOL)

No Abstract Available LBS Management Review Vol.4(2) 1999: 135-147. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/lbsmr.v4i2.24462 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

Total hydrocarbon content (THC) testing in liquid oxygen (LOX) systems

Science.gov (United States)

Meneghelli, B. J.; Obregon, R. E.; Ross, H. R.; Hebert, B. J.; Sass, J. P.; Dirschka, G. E.

2015-12-01

The measured Total Hydrocarbon Content (THC) levels in liquid oxygen (LOX) systems at Stennis Space Center (SSC) have shown wide variations. Examples of these variations include the following: 1) differences between vendor-supplied THC values and those obtained using standard SSC analysis procedures; and 2) increasing THC values over time at an active SSC test stand in both storage and run vessels. A detailed analysis of LOX sampling techniques, analytical instrumentation, and sampling procedures will be presented. Additional data obtained on LOX system operations and LOX delivery trailer THC values during the past 12-24 months will also be discussed. Field test results showing THC levels and the distribution of the THC's in the test stand run tank, modified for THC analysis via dip tubes, will be presented.

Book Review: Building the Team by Chantal Epie | Ovadje | LBS ...

African Journals Online (AJOL)

LBS Management Review. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2004) >. Log in or Register to get access to full text downloads.

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

Science.gov (United States)

Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

2012-10-01

Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland Ltd.

A Generic Framework for Location-Based Services (LBS Provisioning

Directory of Open Access Journals (Sweden)

Ioannis Priggouris

2006-01-01

Full Text Available Location Based Services can be considered as one of the most rapidly expanding fields of the mobile communications sector, with an impressively large application range. The proliferation of mobile/wireless Internet and mobile computing, and the constantly increasing use of handheld, mobile devices and position tracking technologies prepared the grounds for the introduction of this new type of services. The combination of position fixing mechanisms with location-dependent, geographical information, can offer truly customized personal communication services through the mobile phone or other type of devices. Prompted by the avalanche of technology advances in the aforementioned areas in this paper we present an integrated platform for delivering Location Based Services (LBS. The platform covers the full life cycle of a LBS starting from the specification of the service, covering issues like the deployment and maintenance of services, the service invocation and the final delivery of the produced results to the invoking user. A prototype implementation of the discussed platform was developed and used to perform a series of trial services, with the purpose of demonstrating the pursued functionality.

Study of LBS for characterization and analysis of big data benchmarks

International Nuclear Information System (INIS)

Chandio, A.A.; Zhang, F.; Memon, T.D.

2014-01-01

In the past few years, most organizations are gradually diverting their applications and services to Cloud. This is because Cloud paradigm enables (a) on-demand accessed and (b) large data processing for their applications and users on Internet anywhere in the world. The rapid growth of urbanization in developed and developing countries leads a new emerging concept called Urban Computing, one of the application domains that is rapidly deployed to the Cloud. More precisely, in the concept of Urban Computing, sensors, vehicles, devices, buildings, and roads are used as a component to probe city dynamics. Their data representation is widely available including GPS traces of vehicles. However, their applications are more towards data processing and storage hungry, which is due to their data increment in large volume starts from few dozen of TB (Tera Bytes) to thousands of PT (Peta Bytes) (i.e. Big Data). To increase the development and the assessment of the applications such as LBS (Location Based Services), a benchmark of Big Data is urgently needed. This research is a novel research on LBS to characterize and analyze the Big Data benchmarks. We focused on map-matching, which is being used as pre-processing step in many LBS applications. In this preliminary work, this paper also describes current status of Big Data benchmarks and our future direction. (author)

Study on LBS for Characterization and Analysis of Big Data Benchmarks

Directory of Open Access Journals (Sweden)

Aftab Ahmed Chandio

2014-10-01

Full Text Available In the past few years, most organizations are gradually diverting their applications and services to Cloud. This is because Cloud paradigm enables (a on-demand accessed and (b large data processing for their applications and users on Internet anywhere in the world. The rapid growth of urbanization in developed and developing countries leads a new emerging concept called Urban Computing, one of the application domains that is rapidly deployed to the Cloud. More precisely, in the concept of Urban Computing, sensors, vehicles, devices, buildings, and roads are used as a component to probe city dynamics. Their data representation is widely available including GPS traces of vehicles. However, their applications are more towards data processing and storage hungry, which is due to their data increment in large volume starts from few dozen of TB (Tera Bytes to thousands of PT (Peta Bytes (i.e. Big Data. To increase the development and the assessment of the applications such as LBS (Location Based Services, a benchmark of Big Data is urgently needed. This research is a novel research on LBS to characterize and analyze the Big Data benchmarks. We focused on map-matching, which is being used as pre-processing step in many LBS applications. In this preliminary work, this paper also describes current status of Big Data benchmarks and our future direction

Perceptions of preparedness of LBS I teachers in the state of Illinois and graduates of Illinois State University's LBS I program to collaborate in teaching grade 7--12 math, science, and social science

Science.gov (United States)

Caldwell, Janet E.

The expectations for no child to be left behind are leading to increased emphasis on teaching math, science, and social science effectively to students with disabilities. This study utilized information collected from online surveys to examine how current LBS I teachers and individuals graduating from the Illinois State University teacher certification program in LBS I perceive their preparedness to teach these subjects. Participants provided information about coursework and life experiences, and they made suggestions about teacher preparation and professional development programs. Six key items forming the composite variable focused on level of preparation in (a) best practices, (b) selecting materials, (c) selecting objectives, (d) adapting instructional strategies, (e) planning lessons, and (f) and evaluating outcomes. Only 30 LBS I teachers of the 282 contacted by e-mail completed surveys. Of 115 graduates contacted, 71 participated in the original survey and 23 participated in a follow-up survey. Data were analyzed to learn more about the teachers' self-perceptions regarding preparedness to teach math, science, or social science. There was a correlation between perceived level of knowledge and the composite preparation variable for all subjects, but no correlation with length of teaching. Both groups indicated high school content courses were important in preparation to teach. Teachers also indicated collaboration and graduates indicated grade school learning. The most frequent recommendation for both teacher preparation and professional development was additional methods courses. A survey distributed to math, science, and social science teachers of Grades 7--12 asked about their perceptions of the preparedness of LBS I teachers to teach their area of content. Few surveys were completed for each subject so they were examined qualitatively. There was variability among participants, but generally the content area teachers rated themselves as more prepared than

Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD.

Science.gov (United States)

Ambach, Lars; Penitschka, Franziska; Broillet, Alain; König, Stefan; Weinmann, Wolfgang; Bernhard, Werner

2014-10-01

An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN). Copyright © 2014. Published by Elsevier Ireland Ltd.

Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information.

Science.gov (United States)

Ranganathan, Mohini; Radhakrishnan, Rajiv; Addy, Peter H; Schnakenberg-Martin, Ashley M; Williams, Ashley H; Carbuto, Michelle; Elander, Jacqueline; Pittman, Brian; Andrew Sewell, R; Skosnik, Patrick D; D'Souza, Deepak Cyril

2017-10-03

Cannabis and agonists of the brain cannabinoid receptor (CB 1 R) produce acute memory impairments in humans. However, the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans. The objective of this analysis was to determine whether the administration of Δ 9 -Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, impairs encoding and/or retrieval of verbal information. Healthy subjects were recruited from the community. Subjects were administered the Rey-Auditory Verbal Learning Test (RAVLT) either before administration of THC (experiment #1) (n=38) or while under the influence of THC (experiment #2) (n=57). Immediate and delayed recall on the RAVLT was compared. Subjects received intravenous THC, in a placebo-controlled, double-blind, randomized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication. Total immediate recall, short delayed recall, and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC (experiment #2) and not when the RAVLT was administered prior. THC acutely interferes with encoding of verbal memory without interfering with retrieval. These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information. Future studies will be necessary to determine whether THC impairs encoding of non-verbal information, to what extent THC impairs memory consolidation, and the role of other cannabinoids in the memory-impairing effects of cannabis. Cannabinoids, Neural Synchrony, and Information Processing (THC-Gamma) http://clinicaltrials.gov/ct2/show/study/NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http://clinicaltrials.gov/ct2/show/NCT00678730 NCT00678730. Copyright © 2017. Published by Elsevier Inc.

Thermodynamics of the vaporization of non-stoichiometric thorium monocarbide ThC1±x

International Nuclear Information System (INIS)

Yamawaki, Michio; Koyama, Tadafumi; Takahashi, Yoichi

1989-01-01

Vaporization thermodynamics of thorium monocarbide phase ThC 1±x was studied by mass spectrometric Knudsen effusion method at the compositions of ThC 0.891 , ThC 0.975 , ThC 1.007 and ThC 1.074 . The partial vapor pressure of Th(g) and activities of Th and C in ThC 1±x were determined at 2060 to 2330 K. Gibbs energies of formation of ThC 1±x were also determined. Congruent vaporization composition of ThC 1±x was evaluated at 2300 K to be ThC 1.09 . Congruent vaporization and congruent effusing compositions were defined explicitly and their characteristics brought out. (orig.)

Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops.

Science.gov (United States)

Pijlman, F T A; Rigter, S M; Hoek, J; Goldschmidt, H M J; Niesink, R J M

2005-06-01

The total concentration of THC has been monitored in cannabis preparations sold in Dutch coffee shops since 1999. This annual monitoring was issued by the Ministry of Health after reports of increased potency. The level of the main psychoactive compound, Delta9-tetrahydrocannabinol (THC), is measured in marijuana and hashish. A comparison is made between imported and Dutch preparations, and between seasons. Samples of cannabis preparations from randomly selected coffee shops were analyzed using gas chromatography (GC-FID) for THC, CBD and CBN. In 2004, the average THC level of Dutch home-grown marijuana (Nederwiet) (20.4% THC) was significantly higher than that of imported marijuana (7.0% THC). Hashish derived from Dutch marijuana (Nederhasj) contained 39.3% THC in 2004, compared with 18.2% THC in imported hashish. The average THC percentage of Dutch marijuana, Dutch hashish and imported hashish was significantly higher than in previous years. It nearly doubled over 5 years. During this period, the THC percentage in imported marijuana remained unchanged. A higher price had to be paid for cannabis with higher levels of THC. Whether the increase in THC levels causes increased health risks for users can only be concluded when more data are available on adjusted patterns of use, abuse liability, bioavailability and levels of THC in the brain.

Marketing Tool Kit for Nigeria: A Preview | Smith | LBS Management ...

African Journals Online (AJOL)

No Abstract Available LBS Management Review Vol.5(2) 2000: 113-129. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/lbsmr.v5i2.24452 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

Detection time for THC in oral fluid after frequent cannabis smoking.

Science.gov (United States)

Andås, Hilde T; Krabseth, Hege-Merete; Enger, Asle; Marcussen, Bjarne N; Haneborg, An-Magritt; Christophersen, Asbjørg S; Vindenes, Vigdis; Øiestad, Elisabeth L

2014-12-01

The use of oral fluid for detecting drugs of abuse has become increasingly more frequent. Few studies have, however, investigated the detection times for drugs of abuse in oral fluid, compared with that of in urine or in blood. Cannabis is the world's most widely used drug of abuse, and the detection times for cannabis, in different types of matrixes, are therefore important information to the laboratories or institutions performing and evaluating drugs of abuse analyses. It is well known that frequent use of high dosages of cannabis, for longer periods of time, might lead to prolonged detection times for THC-COOH in urine. Cannabis intake is detected in oral fluid as THC, and a positive finding is considered to be a result of recent smoking, although some studies have already reported longer detection times. The aim of this study was to investigate the detection time for THC in oral fluid, collected from drug addicts admitted for detoxification. Findings in oral fluid were compared with findings in urine, among 26 patients admitted to a closed detoxification unit. The study, being the first in doing so, describes the concentration-time profiles for THC in oral fluid among chronic cannabis users, during monitored abstinence, using the Intercept collection kit. The study also includes the concentration-time profiles for creatinine-corrected THC-COOH ratios in urine samples, included to monitor for the possibility of new intakes. THC was detected in oral fluid collected from 11 of the 26 patients in the study. The elimination curves for THC in oral fluid revealed that negative samples could be interspersed among positive samples several days after cessation, whereas the THC-COOH concentrations in urine were decreasing. THC was, in this study, detected in oral fluid for up to 8 days after admission. The study shows that frequent use of high dosages of cannabis may lead to prolonged detection times, and that positive samples can be interspersed among negative samples

Repeatability of oral fluid collection methods for THC measurement

NARCIS (Netherlands)

Houwing, Sjoerd; Smink, Beitske E.; Legrand, Sara-Ann; Mathijssen, Rene P. M.; Verstraete, Alain G.; Brookhuis, Karel A.

2012-01-01

Study objectives: To determine the influence of sample collection for two different collection methods on THC concentrations and to compare THC concentrations collected by both methods. Methods: A total of 136 pairs of oral fluid samples from subjects who had recently smoked Cannabis were obtained

Radioimmunoanalysis of delta-9-THC in blood by means of an 125I tracer

International Nuclear Information System (INIS)

Owens, S.M.; McBay, A.J.; Reisner, H.M.

1982-01-01

A radioimmunoassay for delta-9-THC in plasma, whole blood, or hemolyzed blood specimens has been presented. Samples and standards were diluted with methanol and centrifuged. An aliquot of the supernatant fluid was incubated with RIA buffer, 125 I-labeled delta-8-THC and rabbit anti-THC serum. Solid phase goat anti-rabbit immunoglobulins were added to separate bound from free THC. After centrifugation the supernatant fluid was aspirated and the radioactivity of the precipitate was counted in a gamma counter. The concentration of THC was calculated from a standard curve using the logit-log transformation of the average counts of duplicate tubes. The assay had several advantages. Methanol dilution gave better results than direct analysis. The 125 I-labeled THC had high specific activity and could be counted in a gamma counter. The immunological separation of antibody-bound THC from free THC was better than separation techniques using ammonium sulfate and activated charcoal. THC was determined in 0.1 ml of sample with a sensitivity of 1.5 ng/ml in plasma and 3.0 ng/ml in hemolyzed blood

A Hybrid Smartphone Indoor Positioning Solution for Mobile LBS

Directory of Open Access Journals (Sweden)

Heidi Kuusniemi

2012-12-01

Full Text Available Smartphone positioning is an enabling technology used to create new business in the navigation and mobile location-based services (LBS industries. This paper presents a smartphone indoor positioning engine named HIPE that can be easily integrated with mobile LBS. HIPE is a hybrid solution that fuses measurements of smartphone sensors with wireless signals. The smartphone sensors are used to measure the user’s motion dynamics information (MDI, which represent the spatial correlation of various locations. Two algorithms based on hidden Markov model (HMM problems, the grid-based filter and the Viterbi algorithm, are used in this paper as the central processor for data fusion to resolve the position estimates, and these algorithms are applicable for different applications, e.g., real-time navigation and location tracking, respectively. HIPE is more widely applicable for various motion scenarios than solutions proposed in previous studies because it uses no deterministic motion models, which have been commonly used in previous works. The experimental results showed that HIPE can provide adequate positioning accuracy and robustness for different scenarios of MDI combinations. HIPE is a cost-efficient solution, and it can work flexibly with different smartphone platforms, which may have different types of sensors available for the measurement of MDI data. The reliability of the positioning solution was found to increase with increasing precision of the MDI data.

A hybrid smartphone indoor positioning solution for mobile LBS.

Science.gov (United States)

Liu, Jingbin; Chen, Ruizhi; Pei, Ling; Guinness, Robert; Kuusniemi, Heidi

2012-12-12

Smartphone positioning is an enabling technology used to create new business in the navigation and mobile location-based services (LBS) industries. This paper presents a smartphone indoor positioning engine named HIPE that can be easily integrated with mobile LBS. HIPE is a hybrid solution that fuses measurements of smartphone sensors with wireless signals. The smartphone sensors are used to measure the user's motion dynamics information (MDI), which represent the spatial correlation of various locations. Two algorithms based on hidden Markov model (HMM) problems, the grid-based filter and the Viterbi algorithm, are used in this paper as the central processor for data fusion to resolve the position estimates, and these algorithms are applicable for different applications, e.g., real-time navigation and location tracking, respectively. HIPE is more widely applicable for various motion scenarios than solutions proposed in previous studies because it uses no deterministic motion models, which have been commonly used in previous works. The experimental results showed that HIPE can provide adequate positioning accuracy and robustness for different scenarios of MDI combinations. HIPE is a cost-efficient solution, and it can work flexibly with different smartphone platforms, which may have different types of sensors available for the measurement of MDI data. The reliability of the positioning solution was found to increase with increasing precision of the MDI data.

Repeatability of oral fluid collection methods for THC measurement.

NARCIS (Netherlands)

Houwing, S. Smink, B.E. Legrand, S.-A. Mathijssen, M.P.M. Verstraete, A.G. & Brookhuis, K.A.

2013-01-01

The study objective was to determine the influence of sample collection for two different collection methods on THC concentrations and to compare THC concentrations collected by both methods. A total of 136 pairs of oral fluid samples from subjects who had recently smoked Cannabis were obtained by

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

Science.gov (United States)

Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

2004-09-15

The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development

Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers.

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Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schroeder, Jennifer R; Schwope, David M; Kelly, Deanna L; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

2013-01-01

Δ9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers. Thirteen male chronic daily cannabis smokers (mean ± SD age 24.6± 3.7 years, self-reported smoking frequency of 5.5 ± 5.9 (range 1-24) joint-equivalents daily at study entry) were administered oral THC doses (20 mg) around-the-clock for 7 days (40-120 mg daily) starting the afternoon after admission. The St. Mary's Hospital Sleep Questionnaire was completed every morning. Plasma THC and 11-OH-THC (active metabolite) concentrations were measured in venous blood samples collected every evening. Changes in sleep characteristics over time and associations between sleep characteristics and plasma cannabinoid concentrations were evaluated with repeated measures mixed linear regression. Higher evening THC and 11-OH-THC concentrations were significantly associated with shorter sleep latency, less difficulty falling asleep, and more daytime sleep the following day. In contrast, the duration of calculated and self-reported nighttime sleep decreased slightly (3.54 and 5.34 minutes per night, respectively) but significantly during the study. These findings suggest that tolerance to the somnolent effects of THC may have occurred, but results should be considered preliminary due to design limitations. Somnolence from oral THC may dissipate with chronic, high-dose use. This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment. (Am J Addict 2013;22:510-514). Copyright © American Academy of Addiction Psychiatry.

MOUNTAIN-SCALE COUPLED PROCESSES (TH/THC/THM) MODELS

International Nuclear Information System (INIS)

Y.S. Wu

2005-01-01

This report documents the development and validation of the mountain-scale thermal-hydrologic (TH), thermal-hydrologic-chemical (THC), and thermal-hydrologic-mechanical (THM) models. These models provide technical support for screening of features, events, and processes (FEPs) related to the effects of coupled TH/THC/THM processes on mountain-scale unsaturated zone (UZ) and saturated zone (SZ) flow at Yucca Mountain, Nevada (BSC 2005 [DIRS 174842], Section 2.1.1.1). The purpose and validation criteria for these models are specified in ''Technical Work Plan for: Near-Field Environment and Transport: Coupled Processes (Mountain-Scale TH/THC/THM, Drift-Scale THC Seepage, and Drift-Scale Abstraction) Model Report Integration'' (BSC 2005 [DIRS 174842]). Model results are used to support exclusion of certain FEPs from the total system performance assessment for the license application (TSPA-LA) model on the basis of low consequence, consistent with the requirements of 10 CFR 63.342 [DIRS 173273]. Outputs from this report are not direct feeds to the TSPA-LA. All the FEPs related to the effects of coupled TH/THC/THM processes on mountain-scale UZ and SZ flow are discussed in Sections 6 and 7 of this report. The mountain-scale coupled TH/THC/THM processes models numerically simulate the impact of nuclear waste heat release on the natural hydrogeological system, including a representation of heat-driven processes occurring in the far field. The mountain-scale TH simulations provide predictions for thermally affected liquid saturation, gas- and liquid-phase fluxes, and water and rock temperature (together called the flow fields). The main focus of the TH model is to predict the changes in water flux driven by evaporation/condensation processes, and drainage between drifts. The TH model captures mountain-scale three-dimensional flow effects, including lateral diversion and mountain-scale flow patterns. The mountain-scale THC model evaluates TH effects on water and gas

MOUNTAIN-SCALE COUPLED PROCESSES (TH/THC/THM)MODELS

Energy Technology Data Exchange (ETDEWEB)

Y.S. Wu

2005-08-24

This report documents the development and validation of the mountain-scale thermal-hydrologic (TH), thermal-hydrologic-chemical (THC), and thermal-hydrologic-mechanical (THM) models. These models provide technical support for screening of features, events, and processes (FEPs) related to the effects of coupled TH/THC/THM processes on mountain-scale unsaturated zone (UZ) and saturated zone (SZ) flow at Yucca Mountain, Nevada (BSC 2005 [DIRS 174842], Section 2.1.1.1). The purpose and validation criteria for these models are specified in ''Technical Work Plan for: Near-Field Environment and Transport: Coupled Processes (Mountain-Scale TH/THC/THM, Drift-Scale THC Seepage, and Drift-Scale Abstraction) Model Report Integration'' (BSC 2005 [DIRS 174842]). Model results are used to support exclusion of certain FEPs from the total system performance assessment for the license application (TSPA-LA) model on the basis of low consequence, consistent with the requirements of 10 CFR 63.342 [DIRS 173273]. Outputs from this report are not direct feeds to the TSPA-LA. All the FEPs related to the effects of coupled TH/THC/THM processes on mountain-scale UZ and SZ flow are discussed in Sections 6 and 7 of this report. The mountain-scale coupled TH/THC/THM processes models numerically simulate the impact of nuclear waste heat release on the natural hydrogeological system, including a representation of heat-driven processes occurring in the far field. The mountain-scale TH simulations provide predictions for thermally affected liquid saturation, gas- and liquid-phase fluxes, and water and rock temperature (together called the flow fields). The main focus of the TH model is to predict the changes in water flux driven by evaporation/condensation processes, and drainage between drifts. The TH model captures mountain-scale three-dimensional flow effects, including lateral diversion and mountain-scale flow patterns. The mountain-scale THC model evaluates TH effects on

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC Induces Trophoblast Dysfunction

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Xinwen Chang

2017-06-01

Full Text Available Aims: Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC, the major component of marijuana, on trophoblast function, placental development, and birth outcomes. Methods: The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3 were detected by western blot. Results: We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Conclusion: Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction.

Delta-9 tetrahydrocannabinol (THC inhibits lytic replication of gamma oncogenic herpesviruses in vitro

Directory of Open Access Journals (Sweden)

Friedman Herman

2004-09-01

Full Text Available Abstract Background The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC, has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Methods Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV and Epstein-Barr virus (EBV replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS of monkeys, murine gamma herpesvirus 68 (MHV 68, and herpes simplex type 1 (HSV-1 was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Results Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. Conclusions THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction.

Science.gov (United States)

Chang, Xinwen; Bian, Yiding; He, Qizhi; Yao, Julei; Zhu, Jingping; Wu, Jinting; Wang, Kai; Duan, Tao

2017-01-01

Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC), the major component of marijuana, on trophoblast function, placental development, and birth outcomes. The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC) staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3) were detected by western blot. We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

Inhaled delivery of Δ(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

Science.gov (United States)

Nguyen, Jacques D; Aarde, Shawn M; Vandewater, Sophia A; Grant, Yanabel; Stouffer, David G; Parsons, Loren H; Cole, Maury; Taffe, Michael A

2016-10-01

Most human Δ(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano(®), e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ∼40 min of exposure, was of comparable magnitude (∼3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Persistent effects of chronic Δ9-THC exposure on motor impulsivity in rats.

Science.gov (United States)

Irimia, Cristina; Polis, Ilham Y; Stouffer, David; Parsons, Loren H

2015-08-01

In humans, long-term marijuana use is associated with impaired impulse control and attentional capacity, though it has been difficult to distinguish pre-existing cognitive deficits from possible consequences of prolonged marijuana exposure. To evaluate the effects of long-term exposure to Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent in marijuana, on indices of impulse control and attentional capacity using the rat 5-Choice Serial Reaction Time Task (5-CSRTT). Ten 14-day cycles of Δ9-THC dosing and 5-CSRTT testing were employed, each comprised of 5-day Δ9-THC dosing (0.3 or 3 mg/kg b.i.d.) and 5-CSRTT testing during the 9 days of drug abstinence. Subsequent 5-CSRTT testing continued during 5 weeks of protracted abstinence. Dose-dependent increases in motor impulsivity (premature responses) and behavioral disinhibition (perseverative responses) emerged following 5 cycles of Δ9-THC exposure that persisted for the remaining dosing and testing cycles. Δ9-THC-related disruptions in motor impulsivity and behavioral inhibition were most pronounced during cognitively challenging 5-CSRTT sessions incorporating varying novel inter-trial intervals (ITIs), and these disruptions persisted for at least 5 weeks of Δ9-THC abstinence. Δ9-THC-related impairments in attentional capacity (response accuracy) were also evident during variable ITI challenge tests, though these attentional disruptions abated within 3 weeks of Δ9-THC abstinence. These observations demonstrate that long-term intermittent exposure to clinically meaningful Δ9-THC doses induces persistent impairments in impulse control and attentional function. If present in humans, these disruptions may impact academic and professional performance.

Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

Science.gov (United States)

Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

2013-09-01

Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

Science.gov (United States)

Lee, Dayong; Karschner, Erin L; Milman, Garry; Barnes, Allan J; Goodwin, Robert S; Huestis, Marilyn A

2013-06-01

We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.

TORONTO HARBOUR COMMISSIONERS (THC) SOIL RECYCLE TREATMENT TRAIN - APPLICATIONS ANALYSIS REPORT

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The Toronto Harbour Commissioners (THC) have developed a soil treatment train designed to treat inorganic and organic contaminants in soils. THC has conducted a large-scale demonstration of these technologies in an attempt to establish that contaminated soils at the Toronto Port ...

Effect of oral THC pretreatment on marijuana cue-induced responses in cannabis dependent volunteers.

Science.gov (United States)

Lundahl, Leslie H; Greenwald, Mark K

2015-04-01

The current study tested whether oral Δ(9)-tetrahydrocannabinol (THC: 0-, 10-, and 20-mg) pretreatment would attenuate polysensory cue-induced craving for marijuana. Cannabis dependent participants (7 males and 7 females, who smoked on average 5.4 ± 1.1 blunts daily) completed 3 experimental sessions (oral THC pretreatment dose; counterbalanced order) using a placebo-controlled within-subject crossover design. During each session, participants completed a baseline evaluation and were first exposed to neutral cues then marijuana cues while physiological measures and subjective ratings of mood, craving, and drug effect were recorded. Following placebo oral THC pretreatment, marijuana (vs. neutral) cues significantly increased ratings of marijuana craving (desire and urge to use, Marijuana Craving Questionnaire (MCQ)-Compulsivity scale), anxious mood and feeling hungry. Males also reported feeling more "Down" during marijuana cues relative to females. Pretreatment with oral THC (10-mg and/or 20-mg vs. placebo) significantly attenuated marijuana cue-induced increases in craving and anxiety but not hunger. Oral THC attenuation of the cue-induced increase in MCQ-Compulsivity ratings was observed in females only. Oral THC produced statistically (but not clinically) significant increases in heart rate and decreases in diastolic blood pressure, independent of cues. These marijuana-cue findings replicate earlier results and further demonstrate that oral THC can attenuate selected effects during marijuana multi-cue exposure, and that some of these effects may be sex-related. Results of this study suggest oral THC may be effective for reducing marijuana cue-elicited (conditioned) effects. Further study is needed to determine whether females may selectively benefit from oral THC for this purpose. Copyright © 2015. Published by Elsevier Ireland Ltd.

Rapid elimination of Carboxy-THC in a cohort of chronic cannabis users.

Science.gov (United States)

Lewis, John; Molnar, Anna; Allsop, David; Copeland, Jan; Fu, Shanlin

2016-01-01

Urinary 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (Carboxy-THC) concentrations, normalised to creatinine output, have been demonstrated to be a useful tool in the interpretation of the results of a series of urine tests for cannabis. These tests, often termed historical data, can be used to identify potential chronic cannabis users who may present occupational health and safety risks within the workplace. Conversely, the data can also be used to support employee claims of previous regular, rather than recent, cannabis use. This study aimed at examining the mean elimination of Carboxy-THC in 37 chronic users undergoing voluntary abstinence over a 2-week period. Urine specimens were collected prior to the study and after 1 and 2 weeks of abstinence. Carboxy-THC levels in urine were measured by gas chromatography-mass spectrometry (GC-MS) following alkaline hydrolysis, organic solvent extraction and derivatisation to form its pentafluoropropionic derivative. The creatinine-normalised Carboxy-THC concentrations declined rapidly over the 2 weeks of abstinence period and the majority of chronic cannabis users (73%) reduced their urinary Carboxy-THC levels to below the 15-μg/L confirmatory cutoff within that time. The study further highlights the value of historical urinary Carboxy-THC data as a means of identifying potential occupational health and safety risks among chronic cannabis users.

Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice.

Science.gov (United States)

Walentiny, D Matthew; Vann, Robert E; Wiley, Jenny L

2015-06-01

A number of studies have examined the ability of the endogenous cannabinoid anandamide to elicit Δ(9)-tetrahydrocannabinol (THC)-like subjective effects, as modeled through the THC discrimination paradigm. In the present study, we compared transgenic mice lacking fatty acid amide hydrolase (FAAH), the enzyme primarily responsible for anandamide catabolism, to wildtype counterparts in a THC discrimination procedure. THC (5.6 mg/kg) served as a discriminative stimulus in both genotypes, with similar THC dose-response curves between groups. Anandamide fully substituted for THC in FAAH knockout, but not wildtype, mice. Conversely, the metabolically stable anandamide analog O-1812 fully substituted in both groups, but was more potent in knockouts. The CB1 receptor antagonist rimonabant dose-dependently attenuated THC generalization in both groups and anandamide substitution in FAAH knockouts. Pharmacological inhibition of monoacylglycerol lipase (MAGL), the primary catabolic enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG), with JZL184 resulted in full substitution for THC in FAAH knockout mice and nearly full substitution in wildtypes. Quantification of brain endocannabinoid levels revealed expected elevations in anandamide in FAAH knockout mice compared to wildtypes and equipotent dose-dependent elevations in 2-AG following JZL184 administration. Dual inhibition of FAAH and MAGL with JZL195 resulted in roughly equipotent increases in THC-appropriate responding in both groups. While the notable similarity in THC's discriminative stimulus effects across genotype suggests that the increased baseline brain anandamide levels (as seen in FAAH knockout mice) do not alter THC's subjective effects, FAAH knockout mice are more sensitive to the THC-like effects of pharmacologically induced increases in anandamide and MAGL inhibition (e.g., JZL184). Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats

Energy Technology Data Exchange (ETDEWEB)

Evans, E.B.; Seifen, E.; Kennedy, R.H.; Kafiluddi, R.; Paule, M.G.; Scallet, A.C.; Ali, S.F.; Slikker, W. Jr.

1987-10-01

This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)(/sup 3/H)dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

Sex differences in the subjective effects of oral Δ9-THC in cannabis users.

Science.gov (United States)

Fogel, Jessica S; Kelly, Thomas H; Westgate, Philip M; Lile, Joshua A

2017-01-01

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ 9 -tetrahydrocannabinol (Δ 9 -THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ 9 -THC and placebo and then received a range of Δ 9 -THC doses (0, 5, 15 and a "high" dose of either 25 or 30mg). Responses on a drug-discrimination task, subjective effects questionnaire, psychomotor performance tasks, and physiological measures were assessed. Δ 9 -THC dose-dependently increased drug-appropriate responding, ratings on "positive" Visual Analog Scale (VAS) items (e.g., good effects, like drug, take again), and items related to intoxication (e.g., high, stoned). Δ 9 -THC also dose-dependently impaired performance on psychomotor tasks and elevated heart rate. Sex differences on VAS items emerged as a function of dose. Women exhibited significantly greater subjective responses to oral drug administration than men at the 5mg Δ 9 -THC dose, whereas men were more sensitive to the subjective effects of the 15mg dose of Δ 9 -THC than women. These results demonstrate dose-dependent separation in the subjective response to oral Δ 9 -THC administration by sex, which might contribute to the differential development of problematic cannabis use. Copyright © 2015 Elsevier Inc. All rights reserved.

Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences.

Science.gov (United States)

Wong, Alexander; Keats, Kirily; Rooney, Kieron; Hicks, Callum; Allsop, David J; Arnold, Jonathon C; McGregor, Iain S

2014-10-01

Δ(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in fat tissue where it can remain for prolonged periods. Under conditions of increased fat utilisation, blood cannabinoid concentrations can increase. However, it is unclear whether this has behavioural consequences. Here, we examined whether rats pre-treated with multiple or single doses of THC followed by a washout would show elevated plasma cannabinoids and altered behaviour following fasting or exercise manipulations designed to increase fat utilisation. Behavioural impairment was measured as an inhibition of spontaneous locomotor activity or a failure to successfully complete a treadmill exercise session. Fat utilisation was indexed by plasma free fatty acid (FFA) levels with plasma concentrations of THC and its terminal metabolite (-)-11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THC-COOH) also measured. Rats given daily THC (10 mg/kg) for 5 days followed by a 4-day washout showed elevated plasma THC-COOH when fasted for 24 h relative to non-fasted controls. Fasted rats showed lower locomotor activity than controls suggesting a behavioural effect of fat-released THC. However, rats fasted for 20 h after a single 5-mg/kg THC injection did not show locomotor suppression, despite modestly elevated plasma THC-COOH. Rats pre-treated with THC (5 mg/kg) and exercised 20 h later also showed elevated plasma THC-COOH but did not differ from controls in their likelihood of completing 30 min of treadmill exercise. These results confirm that fasting and exercise can increase plasma cannabinoid levels. Behavioural consequences are more clearly observed with pre-treatment regimes involving repeated rather than single THC dosing.

The relationship between observed signs of impairment and THC concentration in oral fluid.

Science.gov (United States)

Fierro, Inmaculada; González-Luque, Juan Carlos; Alvarez, F Javier

2014-11-01

Studies have shown that cannabis intake increases the risk of traffic accidents. Controlled experiments support these findings and have shown a positive dose-effect relationship. In this retrospective cross-sectional study of data from a roadside survey, we investigated whether a police officer's judgment regarding signs of impairment is related to the concentration of delta-9-tetrahydrocannabinol (THC) in the oral fluid (OF). We investigated 2,632 cases from a representative sample of 3,302 Spanish drivers: 253 drivers positive for THC only, 32 positive for THC and ethanol, 201 with only ethanol detected in their breath, and 2,146 drivers who tested negative for ethanol in breath and drugs in OF. Recorded data comprised breath alcohol concentrations, THC concentrations in the OF, and the 31 observed signs of impairment. Subject groups were compared using the chi-square test, and logistic regression was used to examine the risk of being categorized as exhibiting signs of impairment. A relationship was found between the OF THC concentration and some observed signs of impairment. Eye signs were noticeable from a THC concentration >3.0 ng/ml in OF, and >25 ng/ml was related to behavior, facial expression, and speech signs. Alcohol and THC contribute to impairment independently and, when taken simultaneously, the effects are comparable to the sum of the effects when consumed separately. The observation of signs of impairment due to cannabis occurs in an OF concentration-related manner but, as a clinical test, OF has low sensitivity and specificity in a random roadside survey. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

What’s Around Me?: Applying the Theory of Consumption Values to Understanding the Use of Location-Based Services (LBS) on Smart Phones

OpenAIRE

Jing Zhang; En Mao

2012-01-01

Businesses are increasingly aware of the power of mobile location-based services (LBS) in their success. For consumers, there are abundant options available. To understand the driving factors of consumers’ behavioral intention to use LBS and speak positively about LBS, a model of examining personal values and their influences was developed in this study. The model centers around a set of consumers’ personal consumption values (Sheth et al., 1991a, 1991b), including functional values exemp...

An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

Science.gov (United States)

Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

2013-08-01

Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc

Δ9-THC Disrupts Gamma (γ)-Band Neural Oscillations in Humans.

Science.gov (United States)

Cortes-Briones, Jose; Skosnik, Patrick D; Mathalon, Daniel; Cahill, John; Pittman, Brian; Williams, Ashley; Sewell, R Andrew; Ranganathan, Mohini; Roach, Brian; Ford, Judith; D'Souza, Deepak Cyril

2015-08-01

Gamma (γ)-band oscillations play a key role in perception, associative learning, and conscious awareness and have been shown to be disrupted by cannabinoids in animal studies. The goal of this study was to determine whether cannabinoids disrupt γ-oscillations in humans and whether these effects relate to their psychosis-relevant behavioral effects. The acute, dose-related effects of Δ-9-tetrahydrocannabinol (Δ(9)-THC) on the auditory steady-state response (ASSR) were studied in humans (n=20) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, 0.015, and 0.03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Electroencephalography (EEG) was recorded while subjects listened to auditory click trains presented at 20, 30, and 40 Hz. Psychosis-relevant effects were measured with the Positive and Negative Syndrome scale (PANSS). Δ(9)-THC (0.03 mg/kg) reduced intertrial coherence (ITC) in the 40 Hz condition compared with 0.015 mg/kg and placebo. No significant effects were detected for 30 and 20 Hz stimulation. Furthermore, there was a negative correlation between 40 Hz ITC and PANSS subscales and total scores under the influence of Δ(9)-THC. Δ(9)-THC (0.03 mg/kg) reduced evoked power during 40 Hz stimulation at a trend level. Recent users of cannabis showed blunted Δ(9)-THC effects on ITC and evoked power. We show for the first time in humans that cannabinoids disrupt γ-band neural oscillations. Furthermore, there is a relationship between disruption of γ-band neural oscillations and psychosis-relevant phenomena induced by cannabinoids. These findings add to a growing literature suggesting some overlap between the acute effects of cannabinoids and the behavioral and psychophysiological alterations observed in psychotic disorders.

Central nervous system effects of haloperidol on THC in healthy male volunteers

NARCIS (Netherlands)

Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

2010-01-01

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their

Central nervous system effects of haloperidol on THC in healthy male volunteers

NARCIS (Netherlands)

Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their

Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice

OpenAIRE

Walentiny, D. Matthew; Vann, Robert E.; Wiley, Jenny L.

2015-01-01

A number of studies have examined the ability of the endogenous cannabinoid anandamide to elicit Δ9 -tetrahydrocannabinol (THC)-like subjective effects, as modeled through the THC discrimination paradigm. In the present study, we compared transgenic mice lacking fatty acid amide hydrolase (FAAH), the enzyme primarily responsible for anandamide catabolism, to wildtype counterparts in a THC discrimination procedure. THC (5.6 mg/kg) served as a discriminative stimulus in both genotypes, with sim...

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

Science.gov (United States)

Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

2015-01-01

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical experience with THC:CBD oromucosal spray in patients with multiple sclerosis-related spasticity.

Science.gov (United States)

Koehler, Jürgen; Feneberg, Wolfgang; Meier, Martin; Pöllmann, Walter

2014-09-01

This detailed medical charts' data collection study conducted at a multiple sclerosis (MS) clinic in Germany evaluated the effectiveness of tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray in patients with resistant MS spasticity. Over a 15-month timeframe, THC:CBD spray was initiated in 166 patients. Mean follow-up was 9 months. In all, 120 patients remained on treatment for a response rate of 72%. THC:CBD spray was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. Among responders, the mean spasticity 0-10 numerical rating scale (NRS) score decreased by 57%, from 7.0 before treatment to 3.0 within 10 days of starting THC:CBD spray. The mean dosage was 4 sprays/day. Most patients who withdrew from treatment (40/46) had been receiving THC:CBD spray for less than 60 days. Main reasons for treatment discontinuation were: adverse drug reactions, mainly dizziness, fatigue and oral discomfort (23 patients; 13.9%); lack of efficacy (14 patients; 8.4%); or need for a baclofen pump (9 patients; 5.4%). No new safety signals were noted with THC:CBD spray during the evaluation period. In this routine clinical practice setting at an MS clinic in Germany, THC:CBD spray was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.

Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

Science.gov (United States)

Milman, Garry; Barnes, Allan J; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deana L; Gorelick, David A; Huestis, Marilyn A

2011-08-01

Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.

Reintoxication: the release of fat-stored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure.

Science.gov (United States)

Gunasekaran, N; Long, L E; Dawson, B L; Hansen, G H; Richardson, D P; Li, K M; Arnold, J C; McGregor, I S

2009-11-01

Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg.kg(-1)) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.

Mountain-Scale Coupled Processes (TH/THC/THM)

International Nuclear Information System (INIS)

Dixon, P.

2004-01-01

The purpose of this Model Report is to document the development of the Mountain-Scale Thermal-Hydrological (TH), Thermal-Hydrological-Chemical (THC), and Thermal-Hydrological-Mechanical (THM) Models and evaluate the effects of coupled TH/THC/THM processes on mountain-scale UZ flow at Yucca Mountain, Nevada. This Model Report was planned in ''Technical Work Plan (TWP) for: Performance Assessment Unsaturated Zone'' (BSC 2002 [160819], Section 1.12.7), and was developed in accordance with AP-SIII.10Q, Models. In this Model Report, any reference to ''repository'' means the nuclear waste repository at Yucca Mountain, and any reference to ''drifts'' means the emplacement drifts at the repository horizon. This Model Report provides the necessary framework to test conceptual hypotheses for analyzing mountain-scale hydrological/chemical/mechanical changes and predict flow behavior in response to heat release by radioactive decay from the nuclear waste repository at the Yucca Mountain site. The mountain-scale coupled TH/THC/THM processes models numerically simulate the impact of nuclear waste heat release on the natural hydrogeological system, including a representation of heat-driven processes occurring in the far field. The TH simulations provide predictions for thermally affected liquid saturation, gas- and liquid-phase fluxes, and water and rock temperature (together called the flow fields). The main focus of the TH Model is to predict the changes in water flux driven by evaporation/condensation processes, and drainage between drifts. The TH Model captures mountain-scale three dimensional (3-D) flow effects, including lateral diversion at the PTn/TSw interface and mountain-scale flow patterns. The Mountain-Scale THC Model evaluates TH effects on water and gas chemistry, mineral dissolution/precipitation, and the resulting impact to UZ hydrological properties, flow and transport. The THM Model addresses changes in permeability due to mechanical and thermal disturbances in

Drift-Scale Coupled Processes (DST and THC Seepage) Models

Energy Technology Data Exchange (ETDEWEB)

E. Gonnenthal; N. Spyoher

2001-02-05

The purpose of this Analysis/Model Report (AMR) is to document the Near-Field Environment (NFE) and Unsaturated Zone (UZ) models used to evaluate the potential effects of coupled thermal-hydrologic-chemical (THC) processes on unsaturated zone flow and transport. This is in accordance with the ''Technical Work Plan (TWP) for Unsaturated Zone Flow and Transport Process Model Report'', Addendum D, Attachment D-4 (Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) 2000 [153447]) and ''Technical Work Plan for Nearfield Environment Thermal Analyses and Testing'' (CRWMS M and O 2000 [153309]). These models include the Drift Scale Test (DST) THC Model and several THC seepage models. These models provide the framework to evaluate THC coupled processes at the drift scale, predict flow and transport behavior for specified thermal loading conditions, and predict the chemistry of waters and gases entering potential waste-emplacement drifts. The intended use of this AMR is to provide input for the following: (1) Performance Assessment (PA); (2) Abstraction of Drift-Scale Coupled Processes AMR (ANL-NBS-HS-000029); (3) UZ Flow and Transport Process Model Report (PMR); and (4) Near-Field Environment (NFE) PMR. The work scope for this activity is presented in the TWPs cited above, and summarized as follows: continue development of the repository drift-scale THC seepage model used in support of the TSPA in-drift geochemical model; incorporate heterogeneous fracture property realizations; study sensitivity of results to changes in input data and mineral assemblage; validate the DST model by comparison with field data; perform simulations to predict mineral dissolution and precipitation and their effects on fracture properties and chemistry of water (but not flow rates) that may seep into drifts; submit modeling results to the TDMS and document the models. The model development, input data

Drift-Scale Coupled Processes (DST and THC Seepage) Models

International Nuclear Information System (INIS)

Sonnenthale, E.

2001-01-01

The purpose of this Analysis/Model Report (AMR) is to document the Near-Field Environment (NFE) and Unsaturated Zone (UZ) models used to evaluate the potential effects of coupled thermal-hydrologic-chemical (THC) processes on unsaturated zone flow and transport. This is in accordance with the ''Technical Work Plan (TWP) for Unsaturated Zone Flow and Transport Process Model Report'', Addendum D, Attachment D-4 (Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) 2000 [1534471]) and ''Technical Work Plan for Nearfield Environment Thermal Analyses and Testing'' (CRWMS M and O 2000 [153309]). These models include the Drift Scale Test (DST) THC Model and several THC seepage models. These models provide the framework to evaluate THC coupled processes at the drift scale, predict flow and transport behavior for specified thermal loading conditions, and predict the chemistry of waters and gases entering potential waste-emplacement drifts. The intended use of this AMR is to provide input for the following: Performance Assessment (PA); Near-Field Environment (NFE) PMR; Abstraction of Drift-Scale Coupled Processes AMR (ANL-NBS-HS-000029); and UZ Flow and Transport Process Model Report (PMR). The work scope for this activity is presented in the TWPs cited above, and summarized as follows: Continue development of the repository drift-scale THC seepage model used in support of the TSPA in-drift geochemical model; incorporate heterogeneous fracture property realizations; study sensitivity of results to changes in input data and mineral assemblage; validate the DST model by comparison with field data; perform simulations to predict mineral dissolution and precipitation and their effects on fracture properties and chemistry of water (but not flow rates) that may seep into drifts; submit modeling results to the TDMS and document the models. The model development, input data, sensitivity and validation studies described in this AMR are

LBS Mobile Learning System Based on Android Platform

Directory of Open Access Journals (Sweden)

Zhang Ya-Li

2017-01-01

Full Text Available In the era of mobile internet, PC-end internet services can no long satisfy people’s demands, needs for App and services on mobile phones are more urgent than ever. With increasing social competition, the concept of lifelong learning becomes more and more popular and accepted, making full use of spare time to learn at any time and any place meets updating knowledge desires of modern people, Location Based System (LBS mobile learning system based on Android platform was created under such background. In this Paper, characteristics of mobile location technology and intelligent terminal were introduced and analyzed, mobile learning system which will fulfill personalized needs of mobile learners was designed and developed on basis of location information, mobile learning can be greatly promoted and new research ideas can be expanded for mobile learning.

Compression of ThC to 50 GPa

International Nuclear Information System (INIS)

Gerward, L.; Staun Olsen, J.; Benedict, U.; Luo, H.

1990-01-01

Thorium monocarbide crystallizes in the NaCl type structure (space group Fmanti 3m) at room temperature and atmospheric pressure. Very little has been published on the structural high-pressure behaviour of this compound. In a previous study ThC was compressed to 36 GPa and the bulk modulus B 0 was determined. No phase transformation was observed in contrast to the case of the corresponding uranium compound UC, which transforms to an orthorhombic structure at about 27 GPa. It has been suggested that the B 0 value might be too low, considering the bulk modulus scaling with specific volume for thorium and uranium compounds. Thus it should be useful to confirm the B 0 value for ThC and to look for structural phase transformations in an extended pressure range. (orig.)

Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

Science.gov (United States)

Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

2011-01-01

Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

Significant decreases in frontal and temporal [11C]-raclopride binding after THC challenge.

Science.gov (United States)

Stokes, Paul R A; Egerton, Alice; Watson, Ben; Reid, Alistair; Breen, Gerome; Lingford-Hughes, Anne; Nutt, David J; Mehta, Mitul A

2010-10-01

Delta9-tetrahydrocannabinol (THC) increases prefrontal cortical dopamine release in animals, but this is yet to be examined in humans. In man, striatal dopamine release can be indexed using [11C]-raclopride positron emission tomography (PET), and recent reports suggest that cortical [11C]-raclopride binding may also be sensitive to dopaminergic challenges. Using an existing dataset we examined whether THC alters [11C]-raclopride binding potential (BP(ND)) in cortical regions. Thirteen healthy volunteers underwent two [11C]-raclopride PET scans following either oral 10 mg THC or placebo. Significant areas of decreased cortical [11C]-raclopride BP(ND) were identified using whole brain voxel-wise analysis and quantified using a region of interest (ROI) ratio analysis. Effect of blood flow on binding was estimated using a simplified reference tissue model analysis. Results were compared to [11C]-raclopride test-retest reliability in the ROIs identified using a separate cohort of volunteers. Voxel-wise analysis identified three significant clusters of decreased [11C]-raclopride BP(ND) after THC in the right middle frontal gyrus, left superior frontal gyrus and left superior temporal gyrus. Decreases in [11C]-raclopride BPND following THC were greater than test-retest variability in these ROIs. R1, an estimate of blood flow, significantly decreased in the left superior frontal gyrus in the THC condition but was unchanged in the other ROIs. Decreased frontal binding significantly correlated to catechol-o-methyl transferase (COMT) val108 status. We have demonstrated for the first time significant decreases in bilateral frontopolar cortical and left superior temporal gyrus [11C]-raclopride binding after THC. The interpretation of these findings in relation to prefrontal dopamine release is discussed. Copyright 2010 Elsevier Inc. All rights reserved.

Acute and chronic effects of cannabidiol on Δ⁹-tetrahydrocannabinol (Δ⁹-THC)-induced disruption in stop signal task performance.

Science.gov (United States)

Jacobs, David S; Kohut, Stephen J; Jiang, Shan; Nikas, Spyros P; Makriyannis, Alexandros; Bergman, Jack

2016-10-01

Recent clinical and preclinical research has suggested that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have interactive effects on measures of cognition; however, the nature of these interactions is not yet fully characterized. To address this, we investigated the effects of Δ9-THC and CBD independently and in combination with proposed therapeutic dose ratios of 1:1 and 1:3 Δ9-THC:CBD in adult rhesus monkeys (n = 6) performing a stop signal task (SST). Additionally, the development of tolerance to the effects of Δ9-THC on SST performance was evaluated by determining the effects of acutely administered Δ9-THC (0.1-3.2 mg/kg), during a 24-day chronic Δ9-THC treatment period with Δ9-THC alone or in combination with CBD. Results indicate that Δ9-THC (0.032-0.32 mg/kg) dose-dependently decreased go success but did not alter go reaction time (RT) or stop signal RT (SSRT); CBD (0.1-1.0 mg/kg) was without effect on all measures and, when coadministered in a 1:1 dose ratio, did not exacerbate or attenuate the effects of Δ9-THC. When coadministered in a 1:3 dose ratio, CBD (1.0 mg/kg) attenuated the disruptive effects of 0.32 mg/kg Δ9-THC but did not alter the effects of other Δ9-THC doses. Increases in ED50 values for the effects of Δ9-THC on SST performance were apparent during chronic Δ9-THC treatment, with little evidence for modification of changes in sensitivity by CBD. These results indicate that CBD, when combined with Δ9-THC in clinically available dose ratios, does not exacerbate and, under restricted conditions may even attenuate, Δ9-THC's behavioral effects. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The influence of carbon non-stoichiometry on the electronic properties of thorium monocarbide ThC

International Nuclear Information System (INIS)

Shein, I.R.; Ivanovskii, A.L.

2010-01-01

The first-principle band structure calculations are employed to examine the influence of carbon non-stoichiometry on the structural and electronic properties of the cubic thorium monocarbide ThC. As a result, the equilibrium geometries, electronic bands, densities of states (DOS), Sommerfeld constants and Pauli paramagnetic susceptibility for ThC 1-x (where x = 0, 0.25 and 0.50) are obtained and analyzed in comparison with available experimental data. Additionally, the formation energies of carbon vacancies are theoretically estimated for ThC 1-x . The results obtained indicate that the introduction of carbon vacancies in ThC is accompanied by pronounced DOS changes due to the appearance of novel 'vacancy states' in the near-Fermi region formed by comparable contributions of Th 6d and 5f states. The carbon deficiency strongly affects the structure and stability of thorium carbide. For example, for the hypothetical 'over-deficient' composition ThC 0.50 the initial cubic structure undergoes significant tetragonal distortions. On the contrary, for ThC 0.75 the value of Evf is positive and the cubic structure of this phase is preserved. (authors)

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

Science.gov (United States)

Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

2013-01-01

SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

Science.gov (United States)

Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

The effects of cannabidiol (CBD) on Δ⁹-tetrahydrocannabinol (THC) self-administration in male and female Long-Evans rats.

Science.gov (United States)

Wakeford, Alison G P; Wetzell, Bradley B; Pomfrey, Rebecca L; Clasen, Matthew M; Taylor, William W; Hempel, Briana J; Riley, Anthony L

2017-08-01

Despite widespread cannabis use in humans, few rodent models exist demonstrating significant Δ⁹-tetrahydrocannabinol (THC) self-administration, possibly due to THC's co-occurring aversive effects, which impact drug reinforcement. Cannabis contains a number of phytocannabinoids in addition to THC, one of which, cannabidiol (CBD), has been reported to antagonize some of the aversive effects of THC. Given such effects of CBD, it is possible that it might influence THC intravenous self-administration in rodents. Accordingly, male and female Long-Evans rats were trained to self-administer THC over a 3-week period and then were assessed for the effects of CBD on responding for THC at 1:1 and 1:10 dose ratios or for the establishment of cocaine self-administration (as a positive control for drug self-administration). Consistent with previous research, THC self-administration was modest and only evident in a subset of animals (and unaffected by sex). Cocaine self-administration was high and evident in the majority of animals tested, indicating that the design was sensitive to drug reinforcement. There was no effect of CBD pretreatment on THC intravenous self-administration at any CBD:THC dose ratio. Future developments of animal models of THC self-administration and the examination of factors that affect its display remain important to establish procedures designed to assess the basis for and treatment of cannabis use and abuse. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Morphine decreases social interaction of adult male rats, while THC does not affect it.

Science.gov (United States)

Šlamberová, R; Mikulecká, A; Macúchová, E; Hrebíčková, I; Ševčíková, M; Nohejlová, K; Pometlová, M

2016-12-22

The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.

Characterization of the expression of the thcB gene, coding for a pesticide-degrading cytochrome P-450 in Rhodococcus strains.

OpenAIRE

Shao, Z Q; Behki, R

1996-01-01

A cytochrome P-450 system in Rhodococcus strains, encoded by thcB, thcC, and thcD, participates in the degradation of thiocarbamates and several other pesticides. The regulation of the system was investigated by fusing a truncated lacZ in frame to thcB, the structural gene for the cytochrome P-450 monooxygenase. Analysis of the thcB-lacZ fusion showed that the expression of thcB was 10-fold higher in the presence of the herbicide EPTC (s-ethyl dipropylthiocarbamate). Similar enhancement of th...

Acute and chronic effects of cannabidiol on Δ9-tetrahydrocannabinol (Δ9-THC)-induced disruption in stop signal task performance

Science.gov (United States)

Jacobs, David S.; Kohut, Stephen J.; Jiang, Shan; Nikas, Spyros P.; Makriyannis, Alexandros; Bergman, Jack

2016-01-01

Recent clinical and preclinical research suggests that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have interactive effects on measures of cognition; however, the nature of these interactions is not yet fully characterized. To address this, the effects of Δ9-THC and CBD were investigated independently and in combination with proposed therapeutic dose ratios of 1:1 and 1:3 Δ9-THC:CBD in adult rhesus monkeys (n=6) performing a stop signal task (SST). Additionally, the development of tolerance to the effects of THC on SST performance was evaluated by determining the effects of acutely administered Δ9-THC (0.1-3.2 mg/kg), during a 24-day chronic Δ9-THC treatment period with Δ9-THC alone or with CBD. Results indicate that Δ9-THC (0.032 - 0.32 mg/kg) dose-dependently decreased ‘go’ success but did not alter ‘go’ reaction time or stop signal reaction time (SSRT); CBD (0.1-1.0 mg/kg) was without effect on all measures and, when co-administered in a 1:1 dose-ratio, did not exacerbate or attenuate the effects of Δ9-THC. When co-administered in a 1:3 dose-ratio, CBD (1.0 mg/kg) attenuated the disruptive effects of 0.32 mg/kg Δ9-THC but did not alter the effects of other Δ9-THC doses. Increases in ED50 values for the effects of Δ9-THC on SST performance were apparent during chronic Δ9-THC treatment, with little evidence for modification of changes in sensitivity by CBD. These results indicate that CBD, when combined with THC in clinically available dose-ratios does not exacerbate and, under restricted conditions, may even attenuate Δ9-THC’s behavioral effects. PMID:27690502

Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

Science.gov (United States)

Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

2016-04-05

It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice.

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Bilkei-Gorzo, Andras; Albayram, Onder; Draffehn, Astrid; Michel, Kerstin; Piyanova, Anastasia; Oppenheimer, Hannah; Dvir-Ginzberg, Mona; Rácz, Ildiko; Ulas, Thomas; Imbeault, Sophie; Bab, Itai; Schultze, Joachim L; Zimmer, Andreas

2017-06-01

The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ 9 -tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.

India's first 100,000 lbs/hr atmospheric bed boiler

International Nuclear Information System (INIS)

Mahajan, S.K.

1991-01-01

This paper covers the operating experience at the Petrochemical Complex of Hindustan Polymers, a Member Company of the UB Group, India, on the India's first 100,000 Lbs/hr atmospheric fluidized bed boiler supplied by Bharat Heavy Electricals Ltd., India. This atmospheric fluidized bed boiler is in operation for over 7 years with over 51,000 operating hours. The paper covers the details of onstream hours, actual thermal efficiency achieved, type of coal used and operational advantages of such boilers as per experience of Hindustan Polymers. Paper also highlights the maintenance and equipment problems as well as the developments which have taken place to overcome such problems. Details of experience in the operation of this boiler with baghouse system using abrasive and high ash coal are also covered

Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

Science.gov (United States)

Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-Qian; Wu, Yan; Yang, Hongwei; Tang, Ya-Ping; Sun, Hao; Song, Yunping; Chen, Chu

2013-11-21

Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. Copyright © 2013 Elsevier Inc. All rights reserved.

Combined effects of THC and caffeine on working memory in rats

Science.gov (United States)

Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

2012-01-01

BACKGROUND AND PURPOSE Cannabis and caffeine are two of the most widely used psychoactive substances. Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH Rats were given THC (0, 1 and 3 mg·kg−1, i.p.) along with caffeine (0, 1, 3 and 10 mg·kg−1, i.p.), the selective adenosine A1-receptor antagonist CPT (0, 3 and 10 mg·kg−1) or the selective adenosine A2A-receptor antagonist SCH58261 (0 and 5 mg·kg−1) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS THC alone produced memory deficits at 3 mg·kg−1. The initial exposure to caffeine (10 mg·kg−1) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg−1) was combined with caffeine (10 mg·kg−1) or CPT (10 mg·kg−1), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A1 receptors modulate cannabinoid signalling in the hippocampus. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10

Combined effects of THC and caffeine on working memory in rats.

Science.gov (United States)

Panlilio, Leigh V; Ferré, Sergi; Yasar, Sevil; Thorndike, Eric B; Schindler, Charles W; Goldberg, Steven R

2012-04-01

Cannabis and caffeine are two of the most widely used psychoactive substances. Δ(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. Rats were given THC (0, 1 and 3 mg·kg(-1) , i.p.) along with caffeine (0, 1, 3 and 10 mg·kg(-1) , i.p.), the selective adenosine A(1) -receptor antagonist CPT (0, 3 and 10 mg·kg(-1) ) or the selective adenosine A(2A) -receptor antagonist SCH58261 (0 and 5 mg·kg(-1) ) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. THC alone produced memory deficits at 3 mg·kg(-1) . The initial exposure to caffeine (10 mg·kg(-1) ) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg(-1) ) was combined with caffeine (10 mg·kg(-1) ) or CPT (10 mg·kg(-1) ), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. Published 2011. This article is a U

A comparative genomics approach to find out the probiotic effects of Lactobacillus casei Lbs2 isolated from healthy gut of Indian population

Directory of Open Access Journals (Sweden)

Samrat Ghosh

2017-10-01

Full Text Available Lactobacillae are gram positive diverse group of species and have association with nutrient rich niches like humans, animals and plants. Lactobacillus casei is considered as one of the most competent probiotic throughout the world. Its microbiological feature historically well-established but genomic analysis including comparative genomics is recent. Lactobacillus casei Lbs2 strain was isolated from the gut of a healthy north Indian individual and sequenced. We compared the genomes of Lactobacillus casei Lbs2 with 8 other complete genomes of the same species e.g.;  LC2W, BL23, BDII, W56, 12A, Zhang, LOCK919, ATCC393 using BRIG (Blast Ring Image Generator, Gene enrichment analysis using Fischer Extract test in R. Lbs2 strain has a number of genes including bile tolerance, stress response re-iterating its probiotic stand. Interestingly, genes coding for transposons, co-enzyme transport and metabolisms are enriched in the Indian Genome. Presence of large number of transposons indicates this genome is undergoing expansion and under adaptive selection pressure. When we compared our genome based on Multilocus Sequence Typing (rMLST, we found this strain is closely similar to Lactobacillus fermentum rather than other L. casei strains. Comparison of Lbs2 strain with other L. casei strains indicates ATCC393 (isolated from daily product is closer than others.

Ubiquitous User Localization in LBS - The Need for Implementing Ethical Thinking in Our Research Field

Science.gov (United States)

Retscher, Guenther; Obex, Franz

2015-12-01

Location-based Services (LBS) influence nowadays every individual's life due to the emerging market penetration of smartphones and other mobile devices. For smartphone Apps localization technologies are developed ranging from GNSS beyond to other alternative ubiquitous positioning methods as well as the use of the in-built inertial sensors, such as accelerometers, gyroscopes, magnetometer, barometer, etc. Moreover, signals-of-opportunity which are not intended for positioning at the first sight but are receivable in many environments such as in buildings and public spaces are more and more utilized for positioning and navigation. The use of Wi-Fi (Wireless Fidelity) is a typical example. These technologies, however, have become very powerful tools as the enable to track an individual or even a group of users. Most technical researchers imply that it is mainly about further enhancing technologies and algorithms including the development of new advanced Apps to improve personal navigation and to deliver location oriented information just in time to a single LBS user or group of users. The authors claim that there is a need that ethical and political issues have to be addressed within our research community from the very beginning. Although there is a lot of research going on in developing algorithms to keep ones data and LBS search request in private, researchers can no longer keep their credibility without cooperating with ethical experts or an ethical committee. In a study called InKoPoMoVer (Cooperative Positioning for Real-time User Assistance and Guidance at Multi-modal Public Transit Junctions) a cooperation with social scientists was initiated for the first time at the Vienna University of Technology, Austria, in this context. The major aims of this study in relation to ethical questions are addressed in this paper.

Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

Science.gov (United States)

Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L

2015-09-01

The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

First-principles study of structural, elastic and electronic properties of thorium dicarbide (ThC2) polymorphs

International Nuclear Information System (INIS)

Shein, I.R.; Ivanovskii, A.L.

2009-01-01

The comparative study of the structural, elastic, cohesive and electronic properties of three polymorphs (α-monoclinic, β-tetragonal and γ-cubic) of thorium dicarbide ThC 2 is performed within the density-functional theory. The optimized atomic coordinates, lattice parameters, theoretical density (ρ), bulk moduli (B), compressibility (β), as well as electronic densities of states, electronic heat capacity (γ) and molar Pauli paramagnetic susceptibility (χ) for all ThC 2 polymorphs are obtained and analyzed in comparison with available experimental data. The peculiarities of inter-atomic bonding for thorium dicarbide are discussed. Besides, we have evaluated the formation energies (E f ) of ThC 2 polymorphs for different possible preparation routes (namely for the reactions with the participation of simple substances (metallic Th and graphite) or thorium monocarbide ThC and graphite). The results show that the synthesis of the ThC 2 polymorphs from simple substances is more favorable - in comparison with the reactions with participation of Th monocarbide.

Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Δ⁹-THC.

Science.gov (United States)

Coskun, Zeynep Mine; Bolkent, Sema

2014-10-01

The objectives of study were (a) to determine alteration of feeding, glucose level and oxidative stress and (b) to investigate expression and localization of cannabinoid receptors in type-2 diabetic rat pancreas treated with Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Rats were randomly divided into four groups: control, Δ(9)-THC, diabetes and diabetes + Δ(9)-THC groups. Diabetic rats were treated with a single dose of nicotinamide (85 mg/kg) 15 min before injection of streptozotocin (65 mg/kg). Δ(9)-THC was administered intraperitoneally at 3 mg/kg/day for 7 days. Body weights and blood glucose level of rats in all groups were measured on days 0, 7, 14 and 21. On day 15 after the Δ(9)-THC injections, pancreatic tissues were removed. Blood glucose levels and body weights of diabetic rats treated with Δ(9)-THC did not show statistically significant changes when compared with the diabetic animals on days 7, 14 and 21. Treatment with Δ(9)-THC significantly increased pancreas glutathione levels, enzyme activities of superoxide dismutase and catalase in diabetes compared with non-treatment diabetes group. The cannabinoid 1 receptor was found in islets, whereas the cannabinoid 2 receptor was found in pancreatic ducts. Their localization in cells was both nuclear and cytoplasmic. We can suggest that Δ(9) -THC may be an important agent for the treatment of oxidative damages induced by diabetes. However, it must be supported with anti-hyperglycaemic agents. Furthermore, the present study for the first time emphasizes that Δ(9)-THC may improve pancreatic cells via cannabinoid receptors in diabetes. The aim of present study was to elucidate the effects of Δ(9)-THC, a natural cannabinoid receptor agonist, on the expression and localization of cannabinoid receptors, and oxidative stress statue in type-2 diabetic rat pancreas. Results demonstrate that the cannabinoid receptors are presented in both Langerhans islets and duct regions. The curative effects

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a κ-Opioid Agonist in THC-Treated Mice.

Science.gov (United States)

Chopda, Girish R; Parge, Viraj; Thakur, Ganesh A; Gatley, S John; Makriyannis, Alexandros; Paronis, Carol A

2016-08-01

Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to >90% of maximal possible effect. Treatment with THC produced 9- and 7-fold rightward shifts of the diuresis and antinociception dose-response curves for THC and, respectively, 7- and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to >35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the Bmax value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis dose-effect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

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Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

2017-10-04

Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.

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Costa, M A; Fonseca, B M; Marques, F; Teixeira, N A; Correia-da-Silva, G

2015-08-06

The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MTT metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired CT differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Acute administration of THC impairs spatial but not associative memory function in zebrafish.

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Ruhl, Tim; Prinz, Nicole; Oellers, Nadine; Seidel, Nathan Ian; Jonas, Annika; Albayram, Onder; Bilkei-Gorzo, Andras; von der Emde, Gerhard

2014-10-01

The present study examined the effect of acute administration of endocannabinoid receptor CB1 ligand ∆-9-tetrahydrocannabinol (THC) on intracellular signalling in the brain and retrieval from two different memory systems in the zebrafish (Danio rerio). First, fish were treated with THC and changes in the phosphorylation level of mitogen-activated protein (MAP) kinases Akt and Erk in the brain were determined 1 h after drug treatment. Next, animals of a second group learned in a two-alternative choice paradigm to discriminate between two colours, whereas a third group solved a spatial cognition task in an open-field maze by use of an ego-allocentric strategy. After memory acquisition and consolidation, animals were pharmacologically treated using the treatment regime as in the first group and then tested again for memory retrieval. We found an enhanced Erk but not Akt phosphorylation suggesting that THC treatment specifically activated Erk signalling in the zebrafish telencephalon. While CB1 agonist THC did not affect behavioural performance of animals in the colour discrimination paradigm, spatial memory was significantly impaired. The effect of THC on spatial learning is probably specific, since neither motor activity nor anxiety-related behaviour was influenced by the drug treatment. That indicates a striking influence of the endocannabinoid system (ECS) on spatial cognition in zebrafish. The results are very coincident with reports on mammals, demonstrating that the ECS is functional highly conserved during vertebrate evolution. We further conclude that the zebrafish provides a promising model organism for ongoing research on the ECS.

Does cannabidiol protect against adverse psychological effects of THC?

Directory of Open Access Journals (Sweden)

Raymond J.M. eNiesink

2013-10-01

Full Text Available The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD. A literature search was performed in the bibliographic databases PubMed, PsycINFO and Web of Science using the keyword ‘cannabidiol.’ After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.

Cannabis and Δ9-tetrahydrocannabinol (THC) for weight loss?

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Le Foll, Bernard; Trigo, Jose M; Sharkey, Keith A; Le Strat, Yann

2013-05-01

Obesity is one of the highest preventable causes of morbidity and mortality in the developed world [1]. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the 'munchies'). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile [2]. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ(9)-tetrahydrocannabinol (THC) present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats.

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Stopponi, Serena; Soverchia, Laura; Ubaldi, Massimo; Cippitelli, Andrea; Serpelloni, Giovanni; Ciccocioppo, Roberto

2014-07-01

Cannabis derivatives are among the most widely used illicit substances among young people. The addictive potential of delta-9-tetrahydrocannabinol (THC), the major active ingredient of cannabis is well documented in scientific literature. However, the consequence of THC exposure during adolescence on occurrence of addiction for other drugs of abuse later in life is still controversial. To explore this aspect of THC pharmacology, in the present study, we treated adolescent rats from postnatal day (PND) 35 to PND-46 with increasing daily doses of THC (2.5-10mg/kg). One week after intoxication, the rats were tested for anxiety-like behavior in the elevated plus maze (EPM) test. One month later (starting from PND 75), rats were trained to operantly self-administer heroin intravenously. Finally, following extinction phase, reinstatement of lever pressing elicited by the pharmacological stressor, yohimbine (1.25mg/kg) was evaluated. Data revealed that in comparison to controls, animals treated with chronic THC during adolescence showed a higher level of anxiety-like behavior. When tested for heroin (20μg per infusion) self-administration, no significant differences were observed in both the acquisition of operant responding and heroin intake at baseline. Noteworthy, following the extinction phase, administration of yohimbine elicited a significantly higher level of heroin seeking in rats previously exposed to THC. Altogether these findings demonstrate that chronic exposure to THC during adolescence is responsible for heightened anxiety and increased vulnerability to drug relapse in adulthood. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans

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D'Souza, Deepak Cyril; Fridberg, Daniel J; Skosnik, Patrick D; Williams, Ashley; Roach, Brian; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R Andrew; Ranganathan, Mohini; Mathalon, Daniel

2012-01-01

Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Δ9-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous Δ9-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory ‘oddball' P300 task). Δ9-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Δ9-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Δ9-THC induced psychotomimetic effects, perceptual alterations, and subjective ‘high' in a dose-dependent manner. Δ9-THC -induced reductions in P3b amplitude correlated with Δ9-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ9-THC, there were no dose-related effects of Δ9-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Δ9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact

Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC).

NARCIS (Netherlands)

Hunault, C.C.; Mensinga, T.T.; Böcker, K.B.E.; Schipper, C.M.; Kruidenier, M.; Leenders, M.E.C.; de Vries, I.; Meulenbelt, J.

2009-01-01

RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). Acute cognitive and psychomotor effects of THC among

Effects of oxidizing adulterants on detection of 11-nor-delta9-THC-9-carboxylic acid in urine.

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Paul, Buddha D; Jacobs, Aaron

2002-10-01

Bleach, nitrite, chromate, and hydrogen peroxide-peroxidase are effective urine adulterants used by the illicit drug users to conceal marijuana-positive results. Methods for detecting nitrite and chromate are available. Effects of other oxidizing agents that could possibly be used as adulterants and are difficult to detect or measure are presented in this report. Urine samples containing 40 ng/mL of 11-nor-delta9-THC-9-carboxylic acid (THC-acid) were treated with 10 mmol/L of commonly available oxidizing agents. Effects of horseradish peroxidase of activity 10 unit/mL and extracts from 2.5 g of red radish (Raphanus sativus, Radicula group), horseradish (Armoracia rusticana), Japanese radish (Raphanus sativus, Daikon group), and black mustard seeds (Brassica nigra), all with 10 mmol/L of hydrogen peroxide, were also examined. After 5 min, 16 h and 48 h of exposure at room temperature (23 degrees C) the specimens were tested by a gas chromatographic-mass spectrometric method for THC-acid. A control group treated with sodium hydrosulfite to reduce the oxidants, was also tested to investigate the effect of oxidizing agents on THC-acid in the extraction method. THC-acid was lost completely in the extraction method when treated with chromate, nitrite, oxone, and hydrogen peroxide/ferrous ammonium sulfate (Fenton's reagent). Some losses were also observed with persulfate and periodate (up to 25%). These oxidants, and other oxidizing agents like permanganate, periodate, peroxidase, and extracts from red radish, horseradish, Japanese radish and black mustard seeds destroyed most of the THC-acid (> 94%) within 48 h of exposure. Chlorate, perchlorate, iodate, and oxychloride under these conditions showed little or no effect. Complete loss was observed when THC-acid was exposed to 50 mmol/L of oxychloride for 48 h. Several oxidizing adulterants that are difficult to test by the present urine adulterant testing methods showed considerable effects on the destruction of THC

A protocol for the delivery of cannabidiol (CBD) and combined CBD and ∆9-tetrahydrocannabinol (THC) by vaporisation.

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Solowij, Nadia; Broyd, Samantha J; van Hell, Hendrika H; Hazekamp, Arno

2014-10-16

Significant interest has emerged in the therapeutic and interactive effects of different cannabinoids. Cannabidiol (CBD) has been shown to have anxiolytic and antipsychotic effects with high doses administered orally. We report a series of studies conducted to determine the vaporisation efficiency of high doses of CBD, alone and in combination with ∆9-tetrahydrocannabinol (THC), to achieve faster onset effects in experimental and clinical trials and emulate smoked cannabis. Purified THC and CBD (40 mg/ml and 100 mg/ml respectively) were loaded onto a liquid absorbing pad in a Volcano vaporiser, vaporised and the vapours quantitatively analysed. Preliminary studies determined 200 mg CBD to be the highest dose effectively vaporised at 230 ° C, yielding an availability of approximately 40% in the vapour phase. Six confirmatory studies examined the quantity of each compound delivered when 200 mg or 4 mg CBD was loaded together with 8 mg of THC. THC showed 55% availability when vaporised alone or with low dose CBD, while large variation in the availability of high dose CBD impacted upon the availability of THC when co-administered, with each compound affecting the vaporisation efficiency of the other in a dynamic and dose-dependent manner. We describe optimised protocols that enable delivery of 160 mg CBD through vaporisation. While THC administration by vaporisation is increasingly adopted in experimental studies, often with oral predosing with CBD to examine interactive effects, no studies to date have reported the administration of CBD by vaporisation. We report the detailed methodology aimed at optimising the efficiency of delivery of therapeutic doses of CBD, alone and in combination with THC, by vaporisation. These protocols provide a technical advance that may inform methodology for clinical trials in humans, especially for examining interactions between THC and CBD and for therapeutic applications of CBD. Current Controlled Trials ISRCTN24109245.

Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

International Nuclear Information System (INIS)

Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr.

1989-01-01

THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

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Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

2016-03-01

Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

[Time profile of serum THC levels in occasional and chronic marihuana smokers after acute drog use - implication for drivind motor vehicles].

Science.gov (United States)

Balíková, Marie; Hložek, Tomáš; Páleníček, Tomáš; Tylš, Filip; Viktorinová, Michaela; Melicher, Tomáš; Androvičová, Renáta; Tomíček, Pavel; Roman, Michal; Horáček, Jiří

2014-01-01

Cannabis consumption has individual influence to cognitive and psychomotor functions of drivers and it has been generally accepted that driving under influence is risky in the perspective of traffic safety. However, rules how to assess fitness to drive are not quite clear. The psychoactive compound delta-9-tetrahydrocannabinol (THC) impairs cognition, psychomotor behaviour and driving performance in a dose-related manner approximately. After a single drug dose, THC blood concentration peaks within minutes, before the end of smoking, with a subsequent rapid decrease to the analytical limit of detection. Peak euphoria is delayed compared to THC peak blood concentration and physiological and behavioural effects return to baseline within 3-5 hours. In chronic users, the lipophilic THC accumulates in fat tissues, where its slow redistribution into blood is the rate limiting process in its terminal elimination. In our experimental study we have attempted to contribute to this discussion with results obtained from human volunteers - cannabis consumers in Czech Republic. Aim of our study was to document the time profile of serum THC level in occasional and chronic cannabis users. The observational interval covered the time immediately after the drug consumption (an own cigarette/joint) till 24 hours after. Our preliminary results have shown that in occasional users, THC serum levels cannot be detected already 4 hours after usual cannabis dose, whereas in chronic users measurable THC concentrations in serum persist longer. Moreover, some chronic consumers were practically with permanent THC detection during our observation period and also the chronic users consumed higher THC doses significantly related to doses in occasional ones. Presented results of the experimental study with human volunteers confirm a great individual variability of the kinetic profile of THC in blood due to complicated redistribution. The practical forensic question is how long the psychotropic

A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.

Science.gov (United States)

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-04-01

To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects. Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC). Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported. The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

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Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

40 CFR 63.3555 - How do I determine the outlet THC emissions and add-on control device emission destruction or...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true How do I determine the outlet THC.../outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and add-on control... section to determine either the outlet THC emissions or add-on control device emission destruction or...

An Effective Privacy Architecture to Preserve User Trajectories in Reward-Based LBS Applications

Directory of Open Access Journals (Sweden)

A S M Touhidul Hasan

2018-02-01

Full Text Available How can training performance data (e.g., running or walking routes be collected, measured, and published in a mobile program while preserving user privacy? This question is becoming important in the context of the growing use of reward-based location-based service (LBS applications, which aim to promote employee training activities and to share such data with insurance companies in order to reduce the healthcare insurance costs of an organization. One of the main concerns of such applications is the privacy of user trajectories, because the applications normally collect user locations over time with identities. The leak of the identified trajectories often results in personal privacy breaches. For instance, a trajectory would expose user interest in places and behaviors in time by inference and linking attacks. This information can be used for spam advertisements or individual-based assaults. To the best of our knowledge, no existing studies can be directly applied to solve the problem while keeping data utility. In this paper, we identify the personal privacy problem in a reward-based LBS application and propose privacy architecture with a bounded perturbation technique to protect user’s trajectory from the privacy breaches. Bounded perturbation uses global location set (GLS to anonymize the trajectory data. In addition, the bounded perturbation will not generate any visiting points that are not possible to visit in real time. The experimental results on real-world datasets demonstrate that the proposed bounded perturbation can effectively anonymize location information while preserving data utility compared to the existing methods.

Potency of delta 9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology.

Science.gov (United States)

Potter, David J; Clark, Peter; Brown, Marc B

2008-01-01

Gas chromatography was used to study the cannabinoid content ("potency") of illicit cannabis seized by police in England in 2004/5. Of the four hundred and fifty two samples, indoor-grown unpollinated female cannabis ("sinsemilla") was the most frequent form, followed by resin (hashish) and imported outdoor-grown herbal cannabis (marijuana). The content of the psychoactive cannabinoid delta 9-tetrahydrocannabinol (THC) varied widely. The median THC content of herbal cannabis and resin was 2.1% and 3.5%, respectively. The median 13.9% THC content of sinsemilla was significantly higher than that recorded in the UK in 1996/8. In sinsemilla and imported herbal cannabis, the content of the antipsychotic cannabinoid cannabidiol (CBD) was extremely low. In resin, however, the average CBD content exceeded that of THC, and the relative proportions of the two cannabinoids varied widely between samples. The increases in average THC content and relative popularity of sinsemilla cannabis, combined with the absence of the anti-psychotic cannabinoid CBD, suggest that the current trends in cannabis use pose an increasing risk to those users susceptible to the harmful psychological effects associated with high doses of THC.

Live and heat-killed probiotic Lactobacillus casei Lbs2 protects from experimental colitis through Toll-like receptor 2-dependent induction of T-regulatory response.

Science.gov (United States)

Thakur, Bhupesh Kumar; Saha, Piu; Banik, George; Saha, Dhira Rani; Grover, Sunita; Batish, Virender Kumar; Das, Santasabuj

2016-07-01

Inflammatory bowel disease (IBD) is a group of inflammatory disorders of the intestine caused by dysregulated T-cell mediated immune response against commensal microflora. Probiotics are reported as therapeutically effective against IBD. However, variable efficacy of the live probiotic strains, difference in survival and persistence in the gut between the strains and the lack of insight into the mechanisms of probiotic action limit optimal therapeutic efficacy. Our aims were to evaluate the lactobacillus strains isolated from the North Indian population for the generation of regulatory cells and cytokines in the intestine, to study their effects on pro-inflammatory mediators in the mouse model of inflammatory bowel disease and to explore the underlying mechanisms of their actions. Among the selected lactobacillus strains, Lactobacillus casei Lbs2 (MTCC5953) significantly suppressed lipopolysaccharide-induced pro-inflammatory cytokine (TNF-alpha, IL-6) secretion. Both live and heat-killed Lbs2 polarized Th0 cells to T-regulatory (Treg) cells in vitro, increased the frequency of FoxP3(+) Treg cells in the mesenteric lymph nodes (MLNs) and alleviated macroscopic and histopathological features of colitis in probiotic-fed mice. Moreover, the levels of IL-12, TNF-alpha and IL-17A were suppressed, while IL-10 and TGF-beta levels were augmented in the colonic tissues of Lbs2-treated mice. The induced Treg (iTreg) cells secreted IL-10 and TGF-beta and exerted suppressive effects on the proliferation of effector T-cells. Adoptive transfer of iTreg cells ameliorated the disease manifestations of murine colitis and suppressed the levels of TNF-alpha and IL-17A. Finally, Lbs2 effects were mediated by Toll-like receptor 2 (TLR2) activation on the dendritic cells. This study identified live and heat-killed Lbs2 as putative therapeutic candidates against IBD and highlighted their Toll-like receptor 2-dependent immunomodulatory and regulatory function. Copyright © 2016 Elsevier B

Thc6 protein, isolated from Trichoderma harzianum, can induce maize defense response against Curvularia lunata.

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Fan, Lili; Fu, Kehe; Yu, Chuanjin; Li, Yingying; Li, Yaqian; Chen, Jie

2015-05-01

Mutant T66 was isolated from 450 mutants (constructed with Agrobacterium tumefaciens-mediated transformation method) of Trichoderma harzianum. Maize seeds coated with T66 were more susceptible to Curvularia lunata when compared with those coated with wild-type (WT) strain. The disease index of maize treated with T66 and WT were 62.5 and 42.1%, respectively. Further research showed T-DNA has inserted into the ORF of one gene, which resulted in the functional difference between WT and T66. The gene was cloned and named Thc6, which encodes a novel 327 amino acid protein. To investigate its function, we obtained knockout, complementation, and overexpression mutants of Thc6. Challenge inoculation studies suggested that the Thc6 overexpression mutant can reduce the disease index of maize inbred line Huangzao 4 against the leaf spot pathogen (C. lunata). Meanwhile, The Thc6 mutants were found to affect the resistance of maize inbred line Huangzao 4 against C. lunata by enhancing the activation of jasmonate-responsive genes expression. Liquid chromatography-mass spectrometry (LC-MS) data further confirmed that the concentration of jasmonate in the induced maize exhibits a parallel change tendency with the expression level of defense-related genes. Hence, the Thc6 gene could be participated in the induced resistance of maize inbred line Huangzao 4 against C. lunata infection through a jasmonic acid-dependent pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dose-related effects of delta-9-THC on emotional responses to acute psychosocial stress.

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Childs, Emma; Lutz, Joseph A; de Wit, Harriet

2017-08-01

Cannabis smokers often report that they use the drug to relax or to relieve emotional stress. However, few clinical studies have shown evidence of the stress-relieving effects of cannabis or cannabinoid agonists. In this study, we sought to assess the influence of delta-9-tetrahydrocannabinol (THC), a main active ingredient of cannabis, upon emotional responses to an acute psychosocial stressor among healthy young adults. Healthy volunteers (N=42) participated in two experimental sessions, one with psychosocial stress (Trier Social Stress Test, TSST) and another with a non-stressful task, after receiving 0 (N=13), 7.5mg (N=14) or 12.5mg (N=15) oral THC. Capsules were administered under randomized, double blind conditions, 2.5h before the tasks began. We measured subjective mood and drug effects, vital signs and salivary cortisol before and at repeated times after the capsule and tasks. Subjects also appraised the tasks, before and after completion. In comparison to placebo, 7.5mg THC significantly reduced self-reported subjective distress after the TSST and attenuated post-task appraisals of the TSST as threatening and challenging. By contrast, 12.5mg THC increased negative mood overall i.e., both before and throughout the tasks, and pre-task ratings of the TSST as threatening and challenging. It also impaired TSST performance and attenuated blood pressure reactivity to the stressor. Our findings suggest that a low dose of THC produces subjective stress-relieving effects in line with those commonly reported among cannabis users, but that higher doses may non-specifically increase negative mood. Copyright © 2017. Published by Elsevier B.V.

Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.

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Todd, Stephanie M; Zhou, Cilla; Clarke, David J; Chohan, Tariq W; Bahceci, Dilara; Arnold, Jonathon C

2017-02-01

The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation. Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway. After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. CBD also slightly reduced the acute effects of THC on sensorimotor gating. These subtle effects were found at a 1:1 CBD:THC dose ratio but were not accentuated by a 5:1 dose ratio. CBD did not alter the trajectory of enduring THC-induced anxiety nor tolerance to the pharmacological effects of THC. There was no evidence of CBD potentiating the behavioural effects of THC. However we demonstrated for the first time that repeated co-administration of CBD and THC increased histone 3 acetylation (H3K9/14ac) in the VTA and ΔFosB expression in the nucleus accumbens. These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats.

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Pari, Leelavinothan; Amali, D Rosalin

2005-04-30

Tetrahydrocurcumin (THC) is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of THC and curcumin against chloroquine (CQ) induced hepatotoxicity were studied in female Wistar rats. On single oral administration of CQ (970 mg/kg body weight) the activities of serum marker enzymes namely aspartate transaminase, alanine transaminase and alkaline phosphatase and the levels of bilirubin were significantly increased with significant alterations of lipids in serum and lipidperoxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides in plasma and liver were also elevated in CQ treated rats. The levels of non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) and enzymic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) were also decreased in CQ treated rats. Administration of THC (80 mg/kg body weight) and curcumin (80 mg/kg body weight) for 8 days before and 7 days after single administration of CQ significantly decreased the activities of serum markers and lipids in serum. In addition, the level of TBARS and hydroperoxides were significantly decreased with significant increase in non-enzymic and enzymic antioxidants on treatment with THC and curcumin. The biochemical observation was supplemented by histopathological examination of liver section. The results of the study reveal that THC shows more pronounced protective effect than curcumin against CQ induced toxicity.

THC-MP: High performance numerical simulation of reactive transport and multiphase flow in porous media

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Wei, Xiaohui; Li, Weishan; Tian, Hailong; Li, Hongliang; Xu, Haixiao; Xu, Tianfu

2015-07-01

The numerical simulation of multiphase flow and reactive transport in the porous media on complex subsurface problem is a computationally intensive application. To meet the increasingly computational requirements, this paper presents a parallel computing method and architecture. Derived from TOUGHREACT that is a well-established code for simulating subsurface multi-phase flow and reactive transport problems, we developed a high performance computing THC-MP based on massive parallel computer, which extends greatly on the computational capability for the original code. The domain decomposition method was applied to the coupled numerical computing procedure in the THC-MP. We designed the distributed data structure, implemented the data initialization and exchange between the computing nodes and the core solving module using the hybrid parallel iterative and direct solver. Numerical accuracy of the THC-MP was verified through a CO2 injection-induced reactive transport problem by comparing the results obtained from the parallel computing and sequential computing (original code). Execution efficiency and code scalability were examined through field scale carbon sequestration applications on the multicore cluster. The results demonstrate successfully the enhanced performance using the THC-MP on parallel computing facilities.

Brain imaging study of the acute effects of Delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana.

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Weinstein, Aviv; Brickner, Orit; Lerman, Hedva; Greemland, Mazal; Bloch, Miki; Lester, Hava; Chisin, Roland; Mechoulam, Raphael; Bar-Hamburger, Rachel; Freedman, Nanette; Even-Sapir, Einat

2008-01-01

Twelve regular users of marijuana underwent two positron emission tomography (PET) scans using [18F] Fluorodeoxyglucose (FDG), one while subject to the effects of 17 mg THC, the other without THC. In both sessions, a virtual reality maze task was performed during the FDG uptake period. When subject to the effects of 17 mg THC, regular marijuana smokers hit the walls more often on the virtual maze task than without THC. Compared to results without THC, 17 mg THC increased brain metabolism during task performance in areas that are associated with motor coordination and attention in the middle and medial frontal cortices and anterior cingulate, and reduced metabolism in areas that are related to visual integration of motion in the occipital lobes. These findings suggest that in regular marijuana users, the immediate effects of marijuana may impact on cognitive-motor skills and brain mechanisms that modulate coordinated movement and driving.

Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

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Llorente-Berzal, Alvaro; Puighermanal, Emma; Burokas, Aurelijus; Ozaita, Andrés; Maldonado, Rafael; Marco, Eva M.; Viveros, Maria-Paz

2013-01-01

Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs. PMID:24223797

Sex-dependent psychoneuroendocrine effects of THC and MDMA in an animal model of adolescent drug consumption.

Directory of Open Access Journals (Sweden)

Alvaro Llorente-Berzal

Full Text Available Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46, MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB, whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

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Gaffal, E; Cron, M; Glodde, N; Tüting, T

2013-08-01

∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hair analysis for Δ(9) -tetrahydrocannabinolic acid A (THCA-A) and Δ(9) -tetrahydrocannabinol (THC) after handling cannabis plant material.

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Moosmann, Bjoern; Roth, Nadine; Auwärter, Volker

2016-01-01

A previous study has shown that Δ(9) -tetrahydrocannabinolic acid A (THCA-A), the non-psychoactive precursor of Δ(9) -tetrahydrocannabinol (THC) in the cannabis plant does not get incorporated in relevant amounts into the hair through the bloodstream after repeated oral intake. However, THCA-A can be measured in forensic hair samples in concentrations often exceeding the detected THC concentrations. To investigate whether the handling of cannabis plant material prior to consumption is a contributing factor for THC-positive hair results and also the source for THCA-A findings in hair, a study comprising ten participants was conducted. In this study, the participants rolled a marijuana joint on five consecutive days and hair samples of each participant were obtained. Urine samples were taken to exclude cannabis consumption prior to and during the study. THCA-A and THC could be detected in the hair samples from all participants taken at the end of the exposure period (concentration range: 15-1800 pg/mg for THCA-A and THC). Four weeks after the first exposure, THCA-A could still be detected in the hair samples of nine participants (concentration range: 4-57 pg/mg). Furthermore, THC could be detected in the hair samples of five participants (concentration range: THC as well as the major part of THCA-A found in routine hair analysis derives from external contamination caused by direct transfer through contaminated fingers. This finding is of particular interest in interpreting THC-positive hair results of children or partners of cannabis users, where such a transfer can occur due to close body contact. Analytical findings may be wrongly interpreted as a proof of consumption or at least passive exposure to cannabis smoke. Such misinterpretation could lead to severe consequences for the people concerned. Copyright © 2015 John Wiley & Sons, Ltd.

Spot volume exceeds 2 million lbs (again); restricted price hits $10/lb

International Nuclear Information System (INIS)

Anon.

1995-01-01

This article is the January 1995 uranium market summary. Volume on the spot concentrates market exceeded 2 million lbs equivalent for the second consecutive month. Six deals took place; four in the spot concentrates market, one in the conversion market, and one in the enrichment market. No deals took place in the medium or long-term market. The upper end of the restricted price range reached $10.00 per lb U3O8, its highest level since December 1993. The lower end of the restricted price range strengthened to $9.75. The lower end of the spot conversion price range strengthed to $5.70 per kg U, and SWU prices firmed to the $75.00 to $87.00 level

Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

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Mathai, David S; Holst, Manuela; Rodgman, Christopher; Haile, Colin N; Keller, Jake; Hussain, Mariyah Z; Kosten, Thomas R; Newton, Thomas F; Verrico, Christopher D

2018-01-01

The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC. Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day). Compared with performance at baseline, THC negatively affected accuracy on spatial working memory trials while participants were maintained on placebo (p=0.012) but not guanfacine (p=0.497); compared with placebo, accuracy was significantly (p=0.003, Cohen's d=-0.640) improved while individuals were treated with guanfacine. Similarly, compared with baseline, THC increased omission errors on an attentional task while participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); compared with placebo, there were significantly (p=0.034, Cohen's d=0.838) fewer omissions while individuals were maintained on guanfacine. Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment. Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.

Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

OpenAIRE

Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-qian; Wu, Yan; Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

2013-01-01

Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmaco...

Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC on learning in female rats

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Peter J Winsauer

2015-07-01

Full Text Available The effects of hormone status and age on the development of tolerance to D9-THC were assessed in sham-operated (intact or ovariectomized (OVX female rats that received either intraperitoneal saline or 5.6 mg/kg of D9-THC daily from postnatal day (PD 75 to 180 (early adulthood onward or PD 35 to 140 (adolescence onward. During this time, the 4 groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC were trained in a learning and performance procedure and dose-effect curves were established for D9-THC (0.56-56 mg/kg and the cannabinoid type-1 receptor (CB1R antagonist rimonabant (0.32-10 mg/kg. Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic D9-THC, all of the D9-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic D9-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R and HSP90β (a molecular chaperone modulated by AHA-1 was affected more by OVX than chronic D9-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal BDNF expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (D9-THC on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

Functional interaction and cross-tolerance between ethanol and Δ9-THC: possible modulation by mouse cerebellar adenosinergic A1/GABAergic-A receptors.

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Dar, M Saeed

2014-08-15

We have previously shown a functional motor interaction between ethanol and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) that involved cerebellar adenosinergic A1 and GABAergic A receptor modulation. We now report the development of cross-tolerance between intracerebellar Δ(9)-THC and intraperitoneal ethanol using ataxia as the test response in male CD-1 mice. The drugs [Δ(9)-THC (20 μg), N(6)-cyclohexyladenosine, CHA (12 ng), muscimol (20 ng)] used in the study were directly microinfused stereotaxically via guide cannulas into the cerebellum except ethanol. Δ(9)-THC, infused once daily for 5 days followed 16 h after the last infusion by acute ethanol (2g/kg) and Rotorod evaluation, virtually abolished ethanol ataxia indicating development of cross-tolerance. The cross-tolerance was also observed when the order of ethanol and Δ(9)-THC treatment was reversed, i.e., ethanol injected once daily for 5 days followed 16 h after the last ethanol injection by Δ(9)-THC infusion. The cross-tolerance appeared within 24-48 h, lasted over 72 h and was maximal in 5-day ethanol/Δ(9)-THC-treated animals. Finally, tolerance in chronic ethanol/Δ(9)-THC/-treated animals developed not only to ethanol/Δ(9)-THC-induced ataxia, respectively, but also to the ataxia potentiating effect of CHA and muscimol, indicating modulation by cerebellar adenosinergic A1 and GABAA receptors. A practical implication of these results could be that marijuana smokers may experience little or no negative effects such as ataxia following alcohol consumption. Clinically, such antagonism of ethanol-induced ataxia can be observed in marijuana users thereby encouraging more alcohol consumption and thus may represent a risk factor for the development of alcoholism in this segment of population. Copyright © 2014 Elsevier B.V. All rights reserved.

Transitional Home Care program utilizing the Integrated Practice Unit concept (THC-IPU: Effectiveness in improving acute hospital utilization

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Lian Leng Low

2017-08-01

Full Text Available Background: Organizing care into integrated practice units (IPUs around conditions and patient segments has been proposed to increase value. We organized transitional care into an IPU (THC-IPU for a patient segment of functionally dependent patients with limited community ambulation. Methods: 1,166 eligible patients were approached for enrolment into THC-IPU. THC-IPU patients received a comprehensive assessment within two weeks of discharge; medication reconciliation; education using standardized action plans and a dedicated nurse case manager for up to 90 days after discharge. Patients who rejected enrolment into THC-IPU received usual post-discharge care planned by their attending hospital physician, and formed the control group. The primary outcome was the proportion of patients with at least one unscheduled readmission within 30 days after discharge. Results: We found a statistically significant reduction in 30-day readmissions and emergency department visits in patients on THC-IPU care compared to usual care, even after adjusting for confounders. Conclusion: Delivering transitional care to patients with functional dependence in the form of home visits and organized into an IPU reduced acute hospital utilization in this patient segment. Extending the program into the pre-hospital discharge phase to include discharge planning can have incremental effectiveness in reducing avoidable hospital readmissions.

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

International Nuclear Information System (INIS)

Sarafian, Theodore; Montes, Cindy; Harui, Airi; Beedanagari, Sudheer R.; Kiertscher, Sylvia; Stripecke, Renata; Hossepian, Derik; Kitchen, Christina; Kern, Rita; Belperio, John; Roth, Michael D.

2008-01-01

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ 9 -tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298-306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95-107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p m ) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψ m than did control cells. Since both Ψ m and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK was regulated in a CB2R- and THC

Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

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Winsauer, Peter J; Sutton, Jessie L

2014-02-01

This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

A vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part I: development and validation of a pulmonary cannabinoid route of exposure for experimental pharmacology studies in rodents.

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Manwell, Laurie A; Charchoglyan, Armen; Brewer, Dyanne; Matthews, Brittany A; Heipel, Heather; Mallet, Paul E

2014-01-01

Most studies evaluating the effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) in animal models administer it via a parenteral route (e.g., intraperitoneal (IP) or intravenous injection (IV)), however, the common route of administration for human users is pulmonary (e.g., smoking or vapourizing marijuana). A vapourized Δ(9)-THC delivery system for rodents was developed and used to compare the effects of pulmonary and parenteral Δ(9)-THC administration on blood cannabinoid levels and behaviour. Sprague-Dawley rats were exposed to pulmonary Δ(9)-THC (1, 5, and 10mg of inhaled vapour) delivered via a Volcano® vapourizing device (Storz and Bickel, Germany) or to parenteral Δ(9)-THC (0.25, 0.5, 1.0, and 1.5mg/kg injected IP). Quantification of Δ(9)-THC and its psychoactive metabolite, 11-hydroxy-Δ(9)-THC (11-OH-Δ(9)-THC), in blood was determined by liquid chromatography/mass spectrometry (LC/MS). In order to verify the potential for the vapourization procedure to produce a robust conditioned place preference (CPP) or conditioned place avoidance CPA, classical conditioning procedures were systematically varied by altering the exposure time (10 or 20min) and number of exposed rats (1 or 2) while maintaining the same vapourization dose (10mg). Blood collected at 20min intervals showed similar dose-dependent and time-dependent changes in Δ(9)-THC and 11-OH-Δ(9)-THC for both pulmonary and parenteral administration of Δ(9)-THC. However, vapourized Δ(9)-THC induced CPP under certain conditions whereas IP-administered Δ(9)-THC induced CPA. These results support and extend the limited evidence (e.g., in humans, Naef et al., 2004; in rodents, Niyuhire et al., 2007) that Δ(9)-THC produces qualitatively different effects on behaviour depending upon the route of administration. Copyright © 2014 Elsevier Inc. All rights reserved.

A vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part II: comparison of behavioural effects of pulmonary versus parenteral cannabinoid exposure in rodents.

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Manwell, Laurie A; Ford, Brittany; Matthews, Brittany A; Heipel, Heather; Mallet, Paul E

2014-01-01

Studies of the rewarding and addictive properties of cannabinoids using rodents as animal models of human behaviour often fail to replicate findings from human studies. Animal studies typically employ parenteral routes of administration, whereas humans typically smoke cannabis, thus discrepancies may be related to different pharmacokinetics of parenteral and pulmonary routes of administration. Accordingly, a novel delivery system of vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was developed and assessed for its pharmacokinetic, pharmacodynamic, and behavioural effects in rodents. A commercially available vapourizer was used to assess the effects of pulmonary (vapourized) administration of Δ(9)-THC and directly compared to parenteral (intraperitoneal, IP) administration of Δ(9)-THC. Sprague-Dawley rats were exposed to pure Δ(9)-THC vapour (1, 2, 5, 10, and 20mg/pad), using a Volcano® vapourizing device (Storz and Bickel, Germany) or IP-administered Δ(9)-THC (0.1, 0.3, 0.5, 1.0mg/kg), and drug effects on locomotor activity, food and water consumption, and cross-sensitization to morphine (5mg/kg) were measured. Vapourized Δ(9)-THC significantly increased feeding during the first hour following exposure, whereas IP-administered Δ(9)-THC failed to produce a reliable increase in feeding at all doses tested. Acute administration of 10mg of vapourized Δ(9)-THC induced a short-lasting stimulation in locomotor activity compared to control in the first of four hours of testing over 7days of repeated exposure; this chronic exposure to 10mg of vapourized Δ(9)-THC did not induce behavioural sensitization to morphine. These results suggest vapourized Δ(9)-THC administration produces behavioural effects qualitatively different from those induced by IP administration in rodents. Furthermore, vapourized Δ(9)-THC delivery in rodents may produce behavioural effects more comparable to those observed in humans. We conclude that some of the conflicting findings in animal

Probing the molecular mechanism behind the cognitive impairment induced by THC

Czech Academy of Sciences Publication Activity Database

Botta, J.; Cordomi, A.; Bondar, Alexey; Lazar, Josef; Pardo, L.; McCormick, P. J.

2017-01-01

Roč. 121, č. 2 (2017), s. 11-12 ISSN 1742-7835 Institutional support: RVO:67179843 Keywords : THC * molecular mechanism * cognitive impairment Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Toxicology Impact factor: 3.176, year: 2016

Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease.

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Carroll, C B; Zeissler, M-L; Hanemann, C O; Zajicek, J P

2012-10-01

Δ⁹-tetrahydrocannabinol (Δ⁹-THC) is neuroprotective in models of Parkinson's disease (PD). Although CB1 receptors are increased within the basal ganglia of PD patients and animal models, current evidence suggests a role for CB1 receptor-independent mechanisms. Here, we utilized a human neuronal cell culture PD model to further investigate the protective properties of Δ⁹-THC. Differentiated SH-SY5Y neuroblastoma cells were exposed to PD-relevant toxins: 1-methyl-4-phenylpyridinium (MPP+), lactacystin and paraquat. Changes in CB1 receptor level were determined by quantitative polymerase chain reaction and Western blotting. Cannabinoids and modulatory compounds were co-administered with toxins for 48 h and the effects on cell death, viability, apoptosis and oxidative stress assessed. We found CB1 receptor up-regulation in response to MPP+, lactacystin and paraquat and a protective effect of Δ⁹-THC against all three toxins. This neuroprotective effect was not reproduced by the CB1 receptor agonist WIN55,212-2 or blocked by the CB1 antagonist AM251. Furthermore, the antioxidants α-tocopherol and butylhydroxytoluene as well as the antioxidant cannabinoids, nabilone and cannabidiol were unable to elicit the same neuroprotection as Δ⁹-THC. However, the peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist T0070907 dose-dependently blocked the neuroprotective, antioxidant and anti-apoptotic effects of Δ⁹-THC, while the PPARγ agonist pioglitazone resulted in protection from MPP+-induced neurotoxicity. Furthermore, Δ⁹-THC increased PPARγ expression in MPP+-treated SH-SY5Y cells, another indicator of PPARγ activation. We have demonstrated up-regulation of the CB1 receptor in direct response to neuronal injury in a human PD cell culture model, and a direct neuronal protective effect of Δ⁹-THC that may be mediated through PPARγ activation. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological

Quantification of 11-Carboxy-Delta-9-Tetrahydrocannabinol (THC-COOH) in Meconium Using Gas Chromatography/Mass Spectrometry (GC/MS).

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Peat, Judy; Davis, Brehon; Frazee, Clint; Garg, Uttam

2016-01-01

Maternal substance abuse is an ongoing concern and detecting drug use during pregnancy is an important component of neonatal care when drug abuse is suspected. Meconium is the preferred specimen for drug testing because it is easier to collect than neonatal urine and it provides a much broader time frame of drug exposure. We describe a method for quantifying 11-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in meconium. After adding a labeled internal standard (THC-COOH D9) and acetonitrile, samples are sonicated to release both free and conjugated THC-COOH. The acetonitrile/aqueous layer is removed and mixed with a strong base to hydrolyze the conjugated THC-COOH. The samples are then extracted with an organic solvent mixture as part of a sample "cleanup." The organic solvent layer is discarded and the remaining aqueous sample is acidified. Following extraction with a second organic mixture, the organic layer is removed and concentrated to dryness. The resulting residue is converted to a trimethylsilyl (TMS) derivative and analyzed using gas chromatography/mass spectrometry (GC/MS) in selective ion monitoring (SIM) mode.

How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

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Freeman, Daniel; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M; Harrison, Paul J; Harmer, Catherine J; Cowen, Philip; Morrison, Paul D

2015-03-01

Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.

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Englund, Amir; Atakan, Zerrin; Kralj, Aleksandra; Tunstall, Nigel; Murray, Robin; Morrison, Paul

2016-02-01

Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC. To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers. Ten male cannabis users (THC on the fifth day. THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition (Z=-2.201, p=0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate (Z=-2.193, p=0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ(2)=6.4, p=0.011). THCV in combination with THC significantly increased memory intrusions (Z=-2.155, p=0.031). In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose. © The Author(s) 2015.

Short-term exposure and long-term consequences of neonatal exposure to Δ(9)-tetrahydrocannabinol (THC) and ibuprofen in mice.

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Philippot, Gaëtan; Nyberg, Fred; Gordh, Torsten; Fredriksson, Anders; Viberg, Henrik

2016-07-01

Both Δ(9)-tetrahydrocannabinol (THC) and ibuprofen have analgesic properties by interacting with the cannabinoid receptor type 1 (CB1R) and the cyclooxygenase (COX) systems, respectively. Evaluation of these analgesics is important not only clinically, since they are commonly used during pregnancy and lactation, but also to compare them with acetaminophen, with a known interaction with both CB1R and the COX systems. Short-term exposure of neonatal rodents to acetaminophen during the first weeks of postnatal life, which is comparable with a period from the third trimester of pregnancy to the first years of postnatal life in humans, induces long-term behavioral disturbances. This period, called the brain growth spurt (BGS) and is characterized by series of rapid and fundamental changes and increased vulnerability, peaks around postnatal day (PND) 10 in mice. We therefore exposed male NMRI mice to either THC or ibuprofen on PND 10. At 2 months of age, the mice were subjected to a spontaneous behavior test, consisting of a 60min recording of the variables locomotion, rearing and total activity. Mice exposed to THC, but not ibuprofen, exhibited altered adult spontaneous behavior and habituation capability in a dose-dependent manner. This highlights the potency of THC as a developmental neurotoxicant, since a single neonatal dose of THC was enough to affect adult cognitive function. The lack of effect from ibuprofen also indicates that the previously seen developmental neurotoxicity of acetaminophen is non-COX-mediated. These results might be of importance in future research as well as in the ongoing risk/benefit assessment of THC. Copyright © 2016. Published by Elsevier B.V.

Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

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Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

2015-08-01

Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

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Zamberletti, Erica; Gabaglio, Marina; Grilli, Massimo; Prini, Pamela; Catanese, Alberto; Pittaluga, Anna; Marchi, Mario; Rubino, Tiziana; Parolaro, Daniela

2016-09-01

Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its

Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.

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Rock, Erin M; Limebeer, Cheryl L; Parker, Linda A

2015-12-01

Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.

Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC).

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Mayer, Tzur Alexander; Matar, Michael Alex; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

2014-07-01

The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

Pressure-induced structural transformations and polymerization in ThC2

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Guo, Yongliang; Yu, Cun; Lin, Jun; Wang, Changying; Ren, Cuilan; Sun, Baoxing; Huai, Ping; Xie, Ruobing; Ke, Xuezhi; Zhu, Zhiyuan; Xu, Hongjie

2017-04-01

Thorium-carbon systems have been thought as promising nuclear fuel for Generation IV reactors which require high-burnup and safe nuclear fuel. Existing knowledge on thorium carbides under extreme condition remains insufficient and some is controversial due to limited studies. Here we systematically predict all stable structures of thorium dicarbide (ThC2) under the pressure ranging from ambient to 300 GPa by merging ab initio total energy calculations and unbiased structure searching method, which are in sequence of C2/c, C2/m, Cmmm, Immm and P6/mmm phases. Among these phases, the C2/m is successfully observed for the first time via in situ synchrotron XRD measurements, which exhibits an excellent structural correspondence to our theoretical predictions. The transition sequence and the critical pressures are predicted. The calculated results also reveal the polymerization behaviors of the carbon atoms and the corresponding characteristic C-C bonding under various pressures. Our work provides key information on the fundamental material behavior and insights into the underlying mechanisms that lay the foundation for further exploration and application of ThC2.

Time-dependent effects of repeated THC treatment on dopamine D2/3 receptor-mediated signalling in midbrain and striatum.

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Tournier, Benjamin B; Tsartsalis, Stergios; Dimiziani, Andrea; Millet, Philippe; Ginovart, Nathalie

2016-09-15

This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D2/3R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D2/3R levels in striatum, as assessed using [(3)H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D2/3R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [(3)H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation. Parallel analyses of the psychomotor effects of pre- and post-synaptic doses of quinpirole also showed a pattern of D2/3R functional supersensitivity indicative of more rapid subsidence in striatum than in midbrain following drug cessation. These results indicate that chronic THC is associated with a biochemical and functional sensitization of D2/3R signaling, that these responses show a region-specific temporal pattern and are fully reversible following drug discontinuation. These results suggest that an increased post-synaptic D2/3R function and a decreased DA presynaptic signaling, mediated by increased D2/3R autoinhibition, may predominate during distinct phases of withdrawal and may contribute both to the mechanisms leading to relapse and to cannabinoid withdrawal symptoms. The different rates of normalization of D2/3R function in striatum and midbrain may be critical information for the development of new pharmacotherapies for cannabis dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced discriminative stimulus effects of Δ(9)-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys.

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McMahon, Lance R

2016-08-01

Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ(9)-THC. The extent to which cannabidiol modifies the effects of Δ(9)-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ(9)-tetrahydrocannabinol (Δ(9)-THC; 0.1mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1mg/kg i.v.) while receiving Δ(9)-THC daily (1mg/kg/12hs.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8mg/kg) and 8-OH-DPAT (up to 0.178mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ(9)-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ(9)-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ(9)-THC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Enhanced discriminative stimulus effects of Δ9-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys

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McMahon, Lance R.

2016-01-01

Background Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ9-THC. The extent to which cannabidiol modifies the effects of Δ9-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Methods Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ9-tetrahydrocannabinol (Δ9-THC; 0.1 mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving Δ9-THC daily (1 mg/kg/12 h s.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Results Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8 mg/kg) and 8-OH-DPAT (up to 0.178 mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ9-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. Conclusions These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ9-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ9-THC. PMID:27289270

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

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Maniscalco, Giorgia Teresa; Aponte, R; Bruzzese, D; Guarcello, G; Manzo, V; Napolitano, M; Moreggia, O; Chiariello, F; Florio, C

2018-01-01

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

Impaired functional connectivity of brain reward circuitry in patients with schizophrenia and cannabis use disorder: Effects of cannabis and THC.

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Fischer, Adina S; Whitfield-Gabrieli, Susan; Roth, Robert M; Brunette, Mary F; Green, Alan I

2014-09-01

Cannabis use disorder (CUD) occurs in up to 42% of patients with schizophrenia and substantially worsens disease progression. The basis of CUD in schizophrenia is unclear and available treatments are rarely successful at limiting cannabis use. We have proposed that a dysregulated brain reward circuit (BRC) may underpin cannabis use in these patients. In the present pilot study, we used whole-brain seed-to-voxel resting state functional connectivity (rs-fc) to examine the BRC of patients with schizophrenia and CUD, and to explore the effects of smoked cannabis and orally administered delta-9-tetrahydrocannabinol (THC) on the BRC. 12 patients with schizophrenia and CUD and 12 control subjects each completed two fMRI resting scans, with patients administered either a 3.6% THC cannabis cigarette (n=6) or a 15 mg THC capsule (n=6) prior to their second scan. Results revealed significantly reduced connectivity at baseline in patients relative to controls, with most pronounced hypoconnectivity found between the nucleus accumbens and prefrontal cortical BRC regions (i.e., anterior prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex). Both cannabis and THC administration increased connectivity between these regions, in direct correlation with increases in plasma THC levels. This study is the first to investigate interregional connectivity of the BRC and the effects of cannabis and THC on this circuit in patients with schizophrenia and CUD. The findings from this pilot study support the use of rs-fc as a means of measuring the integrity of the BRC and the effects of pharmacologic agents acting on this circuit in patients with schizophrenia and CUD. Copyright © 2014. Published by Elsevier B.V.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

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Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

2015-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

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Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

The detection of THC, CBD and CBN in the oral fluid of Sativex® patients using two on-site screening tests and LC-MS/MS.

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Molnar, Anna; Fu, Shanlin; Lewis, John; Allsop, David J; Copeland, Jan

2014-05-01

Sativex(®) is an oromucosal spray used to treat spasticity in multiple sclerosis sufferers in some European countries, the United Kingdom, Canada and New Zealand. The drug has also recently been registered by the Therapeutic Goods Administration (TGA) in Australia for treatment of multiple sclerosis. Sativex(®) contains high concentrations of Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), with the former being the subject of random roadside drug tests across Australia to detect cannabis use. This pilot study aims to determine whether or not patients taking Sativex(®) will test positive to THC using these roadside screening tests. Detectable levels of THC, CBD and cannabinol (CBN) in their oral fluid were also confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study was a double-blind, placebo controlled design. Oral fluid was tested prior to and immediately after dosing with either Sativex(®) or placebo at intervals up to 2h after the dose. Two Sativex(®) doses were studied. The low dose contained 5.4mg THC, the high dose 21.6mg THC. Results indicate that the primary screening test used in Australian roadside drug testing, the DrugWipe(®) II Twin, often gave a false negative response for THC, even with high concentrations present. However, secondary screening test, Cozart(®) DDS (used by police after a DrugWipe test gives a positive result), gave true positive results in all cases where patients were being treated with Sativex(®). Confirmatory testing showed high concentrations of THC and CBD (>5356ng/mL THC and >3826ng/mL CBD) in the oral fluid shortly after dosing and also elevated concentrations of CBN. Levels dropped quickly but remained at detectable concentrations (>67.6ng/mL) two hours after drug administration. The average concentration ratio of THC/CBD across all positive samples was 1.10 (%RSD 19.9) reflecting the composition of the Sativex(®) spray. In conclusion, Sativex(®) users may test positive for THC by

Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats.

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Lopez-Rodriguez, Ana Belen; Llorente-Berzal, Alvaro; Garcia-Segura, Luis M; Viveros, Maria-Paz

2014-03-01

Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Δ(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA. Adolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6. © 2013 The British Pharmacological Society.

A PCR marker linked to a THCA synthase polymorphism is a reliable tool to discriminate potentially THC-rich plants of Cannabis sativa L.

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Staginnus, Christina; Zörntlein, Siegfried; de Meijer, Etienne

2014-07-01

Neither absolute THC content nor morphology allows the unequivocal discrimination of fiber cultivars and drug strains of Cannabis sativa L. unequivocally. However, the CBD/THC ratio remains constant throughout the plant's life cycle, is independent of environmental factors, and considered to be controlled by a single locus (B) with two codominant alleles (B(T) and B(D)). The homozygous B(T)/B(T) genotype underlies the THC-predominant phenotype, B(D)/B(D) is CBD predominant, and an intermediate phenotype is induced by the heterozygous state (B(T)/B(D)). Using PCR-based markers in two segregating populations, we proved that the THCA synthase gene represents the postulated B locus and that specific sequence polymorphisms are absolutely linked either to the THC-predominant or the THC-intermediate chemotype. The absolute linkage provides an excellent reliability of the marker signal in forensic casework. For validation, the species-specific marker system was applied to a large number of casework samples and fiber hemp cultivars. © 2014 American Academy of Forensic Sciences.

Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.

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Ali, S F; Newport, G D; Scallet, A C; Paule, M G; Bailey, J R; Slikker, W

1991-11-01

THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Potency trends of delta9-THC and other cannabinoids in confiscated marijuana from 1980-1997.

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ElSohly, M A; Ross, S A; Mehmedic, Z; Arafat, R; Yi, B; Banahan, B F

2000-01-01

The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahydrocannabinol (delta9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of delta9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of delta9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

Strain and sex differences in puberty onset and the effects of THC administration on weight gain and brain volumes.

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Keeley, R J; Trow, J; McDonald, R J

2015-10-01

The use of recreational marijuana is widespread and frequently begins and persists through adolescence. Some research has shown negative consequences of adolescent marijuana use, but this is not seen across studies, and certain factors, like genetic background and sex, may influence the results. It is critical to identify which characteristics predispose an individual to be susceptible to the negative consequences of chronic exposure to marijuana in adolescence on brain health and behavior. To this end, using males and females of two strains of rats, Long-Evans hooded (LER) and Wistar (WR) rats, we explored whether these anatomically and behaviorally dimorphic strains demonstrated differences in puberty onset and strain-specific effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana. Daily 5 mg/kg treatment began on the day of puberty onset and continued for 14 days. Of particular interest were metrics of growth and volumetric estimates of brain areas involved in cognition that contain high densities of cannabinoid receptors, including the hippocampus and its subregions, the amygdala, and the frontal cortex. Brain volumetrics were analyzed immediately following the treatment period. LER and WR females started puberty at different ages, but no strain differences were observed in brain volumes. THC decreased weight gain throughout the treatment period for all groups. Only the hippocampus and some of its subregions were affected by THC, and increased volumes with THC administration was observed exclusively in females, regardless of strain. Long-term treatment of THC did not affect all individuals equally, and females displayed evidence of increased sensitivity to the effects of THC, and by extension, marijuana. Identifying differences in adolescent physiology of WR and LER rats could help determine the cause for strain and sex differences in brain and behavior of adults and help to refine the use of animal models

TECHNOLOGY EVALUATION REPORT: TORONTO HARBOUR COMMISSIONERS (THC) SOIL RECYCLE TREATMENT TRAIN. Project Summary

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A demonstration of the Toronto Harbour Commissioners' (THC) Soil Recycle Treatment Train was performed under the Superfund Innovative Technology Evaluation (SITE) Program at a pilot plant facility in Toronto, Ontario, Canada. The Soil Recycle Treatment Train, which consists of s...

Genetic moderation of the effects of cannabis: catechol-O-methyltransferase (COMT) affects the impact of Δ9-tetrahydrocannabinol (THC) on working memory performance but not on the occurrence of psychotic experiences.

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Tunbridge, Elizabeth M; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Stumpenhorst, Katharina; Harrison, Paul J; Morrison, Paul D; Freeman, Daniel

2015-11-01

Cannabis use can induce cognitive impairments and psychotic experiences. A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val(158)Met) appears to influence the immediate cognitive and psychotic effects of cannabis, or ∆(9)-tetrahydrocannabinol (THC), its primary psychoactive ingredient. This study investigated the moderation of the impact of experimentally administered THC by COMT. Cognitive performance and psychotic experiences were studied in participants without a psychiatric diagnosis, using a between-subjects design (THC vs. placebo). The effect of COMT Val(158)Met genotype on the cognitive and psychotic effects of THC, administered intravenously in a double-blind, placebo-controlled manner to 78 participants who were vulnerable to paranoia, was examined. The results showed interactive effects of genotype and drug group (THC or placebo) on working memory, assayed using the Digit Span Backwards task. Specifically, THC impaired performance in COMT Val/Val, but not Met, carriers. In contrast, the effect of THC on psychotic experiences, measured using the Community Assessment of Psychic Experiences (CAPE) positive dimension, was unaffected by COMT genotype. This study is the largest to date examining the impact of COMT genotype on response to experimentally administered THC, and the first using a purely non-clinical cohort. The data suggest that COMT genotype moderates the cognitive, but not the psychotic, effects of acutely administered THC. © The Author(s) 2015.

In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection.

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Marshell, R; Kearney-Ramos, T; Brents, L K; Hyatt, W S; Tai, S; Prather, P L; Fantegrossi, W E

2014-09-01

Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke these drugs, but preclinical studies usually rely on injection for drug delivery. We used the cannabinoid tetrad and drug discrimination to compare in vivo effects of inhaled drugs with injected doses of these two SCBs, as well as with the phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Mice inhaled various doses of Δ(9)-THC, JWH-018 or JWH-073, or were injected intraperitoneally (IP) with these same compounds. Rectal temperature, tail flick latency in response to radiant heat, horizontal bar catalepsy, and suppression of locomotor activity were assessed in each animal. In separate studies, mice were trained to discriminate Δ(9)-THC (IP) from saline, and tests were performed with inhaled or injected doses of the SCBs. Both SCBs elicited Δ(9)-THC-like effects across both routes of administration, and effects following inhalation were attenuated by pretreatment with the CB1 antagonist/inverse agonist rimonabant. No cataleptic effects were observed following inhalation, but all compounds induced catalepsy following injection. Injected JWH-018 and JWH-073 fully substituted for Δ(9)-THC, but substitution was partial (JWH-073) or required relatively higher doses (JWH-018) when drugs were inhaled. These studies demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor-mediated Δ(9)-THC-like effects in mice when delivered via inhalation or via injection. Across these routes of administration, differences in cataleptic effects and, perhaps, discriminative stimulus effects, may implicate the involvement of active metabolites of these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential effects of presynaptic versus postsynaptic adenosine A2A receptor blockade on Δ9-tetrahydrocannabinol (THC) self-administration in squirrel monkeys.

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Justinová, Zuzana; Redhi, Godfrey H; Goldberg, Steven R; Ferré, Sergi

2014-05-07

Different doses of an adenosine A2A receptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl)ethenyl]-7 methyl-3-[3-(phosphooxy)propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2A receptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynaptic A2A receptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A2A receptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously self-administer THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose-response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A2A receptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.

Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

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Elmes, Matthew W; Kaczocha, Martin; Berger, William T; Leung, KwanNok; Ralph, Brian P; Wang, Liqun; Sweeney, Joseph M; Miyauchi, Jeremy T; Tsirka, Stella E; Ojima, Iwao; Deutsch, Dale G

2015-04-03

Δ(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol.

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Becker, Jérôme A J; Kieffer, Brigitte L; Le Merrer, Julie

2017-09-01

Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse. © 2016 Society for the Study of Addiction.

Morphine Decreases Social Interaction of Adult Male Rats, While THC Does Not Affect It

Czech Academy of Sciences Publication Activity Database

Šlamberová, R.; Mikulecká, Anna; Macúchová, E.; Hrebíčková, I.; Ševčíková, M.; Nohejlová, K.; Pometlová, M.

2016-01-01

Roč. 65, Suppl.5 (2016), S547-S555 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : social behavior * opioids * morphine * cannabinoids * THC * male rats Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

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Keeley, Robin J; Bye, Cameron; Trow, Jan; McDonald, Robert J

2018-01-01

The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9 -tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

Limitations to the Dutch cannabis toleration policy: Assumptions underlying the reclassification of cannabis above 15% THC.

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Van Laar, Margriet; Van Der Pol, Peggy; Niesink, Raymond

2016-08-01

The Netherlands has seen an increase in Δ9-tetrahydrocannabinol (THC) concentrations from approximately 8% in the 1990s up to 20% in 2004. Increased cannabis potency may lead to higher THC-exposure and cannabis related harm. The Dutch government officially condones the sale of cannabis from so called 'coffee shops', and the Opium Act distinguishes cannabis as a Schedule II drug with 'acceptable risk' from other drugs with 'unacceptable risk' (Schedule I). Even in 1976, however, cannabis potency was taken into account by distinguishing hemp oil as a Schedule I drug. In 2011, an advisory committee recommended tightening up legislation, leading to a 2013 bill proposing the reclassification of high potency cannabis products with a THC content of 15% or more as a Schedule I drug. The purpose of this measure was twofold: to reduce public health risks and to reduce illegal cultivation and export of cannabis by increasing punishment. This paper focuses on the public health aspects and describes the (explicit and implicit) assumptions underlying this '15% THC measure', as well as to what extent these are supported by scientific research. Based on scientific literature and other sources of information, we conclude that the 15% measure can provide in theory a slight health benefit for specific groups of cannabis users (i.e., frequent users preferring strong cannabis, purchasing from coffee shops, using 'steady quantities' and not changing their smoking behaviour), but certainly not for all cannabis users. These gains should be weighed against the investment in enforcement and the risk of unintended (adverse) effects. Given the many assumptions and uncertainty about the nature and extent of the expected buying and smoking behaviour changes, the measure is a political choice and based on thin evidence. Copyright © 2016 Springer. Published by Elsevier B.V. All rights reserved.

Δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

International Nuclear Information System (INIS)

Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J.; Aramaki, Hironori

2014-01-01

We recently reported that Δ 9 -tetrahydrocannabinol (Δ 9 -THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ 9 -THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ 9 -THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ 9 -THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ 9 -THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ 9 -THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ 9 -THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ 9 -THC up-regulation of FA2H in MDA-MB-231 cells

Δ(9)-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells.

Science.gov (United States)

Takeda, Shuso; Ikeda, Eriko; Su, Shengzhong; Harada, Mari; Okazaki, Hiroyuki; Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi; Watanabe, Kazuhito; Omiecinski, Curtis J; Aramaki, Hironori

2014-12-04

We recently reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ(9)-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ(9)-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ(9)-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ(9)-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ(9)-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ(9)-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ(9)-THC up-regulation of FA2H in MDA-MB-231 cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Theoretical Insights into Monometallofullerene Th@C76: Strong Covalent Interaction between Thorium and the Carbon Cage.

Science.gov (United States)

Zhao, Pei; Zhao, Xiang; Ehara, Masahiro

2018-03-19

Th@C 76 has been studied by density functional theory combined with statistical mechanics calculations. The results reveal that Th@ T d (19151)-C 76 satisfying the isolated pentagon rule possesses the lowest energy. Nevertheless, considering the enthalpy-entropy interplay, Th@ C 1 (17418)-C 76 with one pair of adjacent pentagons is thermodynamically favorable at elevated temperatures, which is reported for the first time. The bonding critical points in both isomers were analyzed to disclose covalent interactions between the inner Th and cages. In addition, the Wiberg bond orders of M-C bonding in different endohedral metallofullerenes (EMFs) were investigated to prove stronger covalent interactions of Th-C in Th-based EMFs.

Sensitive determination of THC and main metabolites in human plasma by means of microextraction in packed sorbent and gas chromatography-tandem mass spectrometry.

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Rosado, T; Fernandes, L; Barroso, M; Gallardo, E

2017-02-01

Cannabis is one of the most available and consumed illicit drug in the world and its identification and quantification in biological specimens can be a challenge given its low concentrations in body fluids. The present work describes a fast and fully validated procedure for the simultaneous detection and quantification of ▵ 9 -tetrahydrocannabinol (▵ 9_ THC) and its two main metabolites 11-hydroxy ▵ 9_ tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-▵ 9 - tetrahydrocannbinol (THC-COOH) in plasma samples using microextraction by packed sorbent (MEPS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). A small plasma volume (0.25mL) pre-diluted (1:20), was extracted with MEPS M1 sorbent as follows: conditioning (4 cycles of 250μL methanol and 4 cycles of 250μL 0.1% formic acid in water); sample load (26 cycles of 250μL); wash (100μL of 3% acetic acid in water followed by 100μL 5% methanol in water); and elution (6 cycles of 100μL of 10% ammonium hydroxide in methanol). The procedure allowed the quantification of all analytes in the range of 0.1-30ng/mL. Recoveries ranged from 53 to 78% (THC), 57 to 66% (11-OH-THC) and 62 to 65% (THC-COOH), allowing the limits of detection and quantification to be set at 0.1ng/mL for all compounds. Intra-day precision and accuracy revealed coefficients of variation (CVs) lower than 10% at the studied concentrations, with a mean relative error within±9%, while inter-day precision and accuracy showed CVs lower than 15% for all analytes at the tested concentrations, with an inaccuracy within±8%. Copyright © 2016 Elsevier B.V. All rights reserved.

Δ{sup 9}-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

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Takeda, Shuso [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU), 5-1-1 Hiro-koshingai, Kure, Hiroshima 737-0112 (Japan); Ikeda, Eriko [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Su, Shengzhong [Center for Molecular Toxicology and Carcinogenesis, 101 Life Sciences Building, Pennsylvania State University, University Park, PA 16802 (United States); Harada, Mari [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Okazaki, Hiroyuki [Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Yoshioka, Yasushi; Nishimura, Hajime; Ishii, Hiroyuki; Kakizoe, Kazuhiro; Taniguchi, Aya; Tokuyasu, Miki; Himeno, Taichi [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Watanabe, Kazuhito [Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181 (Japan); Omiecinski, Curtis J. [Center for Molecular Toxicology and Carcinogenesis, 101 Life Sciences Building, Pennsylvania State University, University Park, PA 16802 (United States); Aramaki, Hironori [Department of Molecular Biology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan); Drug Innovation Research Center, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511 (Japan)

2014-12-04

We recently reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ{sup 9}-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ{sup 9}-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ{sup 9}-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ{sup 9}-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ{sup 9}-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ{sup 9}-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ{sup 9}-THC up-regulation of FA2H in MDA-MB-231 cells.

Determination of the relative percentage distribution of THCA and Δ(9)-THC in herbal cannabis seized in Austria - Impact of different storage temperatures on stability.

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Taschwer, Magdalena; Schmid, Martin G

2015-09-01

Cannabis is globally by far the most widespread illicit drug of abuse. Especially since its legalization in some of the US, controversies about the legal status of cannabis for recreational and medical use have come up. Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), which is the major active ingredient in cannabis products, is mainly responsible for the psychoactive effects. Its inactive biosynthetic precursor tetrahydrocannabinolic acid (THCA) is present in different quantities in fresh and undried cannabis plants. Under influence of drying, temperature and UV exposure it decomposes to Δ(9)-THC. In this study, a quantification of Δ(9)-THC and THCA was carried out to check the stability of cannabis samples. The determination of the degradation of THCA to Δ(9)-THC in 29 cannabis products seized in Austria was monitored by HPLC-UV. Mobile phase consisted of a 25mM triethylammoniumphosphate buffer (pH 3.0) and acetonitrile (36:64). A common LiChrospher(®) 100 RP-18 column was utilized as stationary phase. To check the influence of low as well as high temperature on the degradation process of the cannabinoid THCA to Δ(9)-THC, samples were stored in a freezer or in a drying cabinet for a specified time period. It was shown successfully that high storage temperatures led to a more rapid and complete decomposition of THCA to Δ(9)-THC while at low temperatures only slight or no changes of the percentage distribution were determined. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Population pharmacokinetics model of THC used by pulmonary route in occasional cannabis smokers.

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Marsot, A; Audebert, C; Attolini, L; Lacarelle, B; Micallef, J; Blin, O

Cannabis is the most widely used illegal drug in the world. Delta-9-tetrahydrocannabinol (THC) is the main source of the pharmacological effect. Some studies have been carried out and showed significant variability in the described models as the values of the estimated pharmacokinetic parameters. The objective of this study was to develop a population pharmacokinetic model for THC in occasional cannabis smokers. Twelve male volunteers (age: 20-28years, body weight: 62.5-91.0kg), tobacco (3-8 cigarette per day) and cannabis occasional smokers were recruited from the local community. After ad libitum smoking cannabis cigarette according a standardized procedure, 16 blood samples up to 72h were collected. Population pharmacokinetic analysis was performed using a non-linear mixed effects model, with NONMEM software. Demographic and biological data were investigated as covariates. A three-compartment model with first-order elimination fitted the data. The model was parameterized in terms of micro constants and central volume of distribution (V 1 ). Normal ALT concentration (6.0 to 45.0IU/l) demonstrated a statistically significant correlation with k 10 . The mean values (%Relative Standard Error (RSE)) for k 10 , k 12 , k 21 , k 23 , k 32 and V 1 were 0.408h -1 (48.8%), 4.070h -1 (21.4%), 0.022h -1 (27.0%), 1.070h -1 (14.3%), 1.060h -1 (16.7%) and 19.10L (39.7%), respectively. We have developed a population pharmacokinetic model able to describe the quantitative relationship between administration of inhaled doses of THC and the observed plasma concentrations after smoking cannabis. In addition, a linear relationship between ALT concentration and value of k 10 has been described and request further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Theoretical study of actinide monocarbides (ThC, UC, PuC, and AmC)

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Pogány, Peter; Kovács, Attila; Visscher, Lucas; Konings, Rudy J. M.

2016-12-01

A study of four representative actinide monocarbides, ThC, UC, PuC, and AmC, has been performed with relativistic quantum chemical calculations. The two applied methods were multireference complete active space second-order perturbation theory (CASPT2) including the Douglas-Kroll-Hess Hamiltonian with all-electron basis sets and density functional theory with the B3LYP exchange-correlation functional in conjunction with relativistic pseudopotentials. Beside the ground electronic states, the excited states up to 17 000 cm-1 have been determined. The molecular properties explored included the ground-state geometries, bonding properties, and the electronic absorption spectra. According to the occupation of the bonding orbitals, the calculated electronic states were classified into three groups, each leading to a characteristic bond distance range for the equilibrium geometry. The ground states of ThC, UC, and PuC have two doubly occupied π orbitals resulting in short bond distances between 1.8 and 2.0 Å, whereas the ground state of AmC has significant occupation of the antibonding orbitals, causing a bond distance of 2.15 Å.

Effects of varying marijuana potency on deposition of tar and delta9-THC in the lung during smoking.

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Matthias, P; Tashkin, D P; Marques-Magallanes, J A; Wilkins, J N; Simmons, M S

1997-12-01

To determine whether smoking more, compared to less, potent marijuana (MJ) cigarettes to a desired level of intoxication ("high") reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and delta9-tetrahydrocannabinol (THC), carboxyhemoglobin (COHb) boost, smoking topography, including cumulative puff volume (CPV) and breathholding time, change in heart rate (deltaHR) and "high" during ad lib smoking of 0, 1.77, and 3.95% MJ cigarettes on 3 separate days. At each session, subjects had access to only a single MJ cigarette. On average, smoking topography and COHb boost did not differ across the different strengths of MJ, while THC delivery, as well as HR, were significantly greater (p studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p marijuana. Under the conditions of this study, we conclude that tar delivery is reduced relative to THC content in a minority of subjects, and this reduction appears to be due to a reduced intake of smoke (decreased CPV) and/or a reduced tar yield from the stronger MJ preparation.

Different effects of chronic THC on the neuroadaptive response of dopamine D2/3 receptor-mediated signaling in roman high- and roman low-avoidance rats.

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Tournier, Benjamin B; Dimiziani, Andrea; Tsartsalis, Stergios; Millet, Philippe; Ginovart, Nathalie

2018-04-01

The Roman high (RHA)- and low (RLA)-avoidance rat sublines have been identified as an addiction-prone and addiction-resistant phenotype based on their high vs. low locomotor responsiveness to novelty and high vs. low ability to develop neurochemical and behavioral sensitization to psychostimulants, respectively. Most studies though have focused on psychostimulants and little is known about the neuroadaptive response of these two lines to cannabinoids. This study investigated the effects of chronic exposure to Δ 9 -tetrahydrocannabinol (THC) on dopamine D 2/3 receptor (D 2/3 R) availabilities and functional sensitivity in the mesostriatal system of RHA and RLA rats. At baseline, RLA rats exhibited higher densities of mesostriatal D2/3R but lower levels of striatal CB 1 R mRNA and displayed a lower locomotor response to acute THC as compared to RHAs. Following chronic THC treatment, striking changes in D 2/3 R signaling were observed in RLA but not in RHA rats, namely an increased availability and functional supersensitivity of striatal D 2/3 R, as evidenced by a supersensitive psychomotor response to the D 2/3 R agonist quinpirole. Moreover, in RLA rats, the lower was the locomotor response to acute THC, the higher was the psychomotor response to quinpirole following chronic THC. These results showing a greater neuroadaptive response of RLA vs. RHA rats to chronic THC thus contrast with previous studies showing a resistance to neuroadaptive response of RLAs to psychostimulants, This suggests that, contrasting with their low proneness to psychostimulant drug-seeking, RLAs may exhibit a heightened proneness to cannabinoid drug-seeking as compared to RHA rats. © 2017 Wiley Periodicals, Inc.

Distribution of Curcumin and THC in Peripheral Blood Mononuclear Cells Isolated from Healthy Individuals and Patients with Chronic Lymphocytic Leukemia.

Science.gov (United States)

Bolger, Gordon T; Licollari, Albert; Tan, Aimin; Greil, Richard; Pleyer, Lisa; Vcelar, Brigitta; Majeed, Muhammad; Sordillo, Peter

2018-01-01

Background/Aim: Curcumin is being widely investigated for its anticancer properties and studies in the literature suggest that curcumin distributes to a higher degree in tumor versus non-tumor cells. In the current study, we report on investigation of the distribution of curcumin and metabolism to THC in PBMC from healthy individuals and chronic lymphocytic leukemia (CLL) patients following exposure to Lipocurc™ (liposomal curcumin). Materials and Methods: The time and temperature-dependent distribution of liposomal curcumin and metabolism to tetrahydrocurcumin (THC) were measured in vitro in human peripheral blood mononuclear cells (PBMC) obtained from healthy individuals, PBMC HI (cryopreserved and freshly isolated PBMC) and CLL patients (cryopreserved PBMC) with lymphocyte counts ranging from 17-58×10 6 cells/ml (PBMC CLL,Grp 1 ) and >150×10 6 cells/ml (PBMC CLL,Grp 2 ). PBMC were incubated in plasma protein supplemented media with Lipocurc™ for 2-16 min at 37°C and 4°C and the cell and medium levels of curcumin determined by LC-MS/MS. Results: PBMC from CLL patients displayed a 2.2-2.6-fold higher distribution of curcumin compared to PBMC HI Curcumin distribution into PBMCCLL, Grp 1/Grp 2 ranged from 384.75 - 574.50 ng/g w.w. of cell pellet and was greater compared to PBMC HI that ranged from 122.27-220.59 ng/g w.w. of cell pellet following incubation for up to 15-16 min at 37°C. The distribution of curcumin into PBMC CLL,Grp 2 was time-dependent in comparison to PBMC HI which did not display a time-dependence and there was no temperature-dependence for curcumin distribution in either cell type. Curcumin was metabolized to THC in PBMC. The metabolism of curcumin to THC was not markedly different between PBMC HI (range=23.94-42.04 ng/g w.w. cell pellet) and PBMC CLL,Grp 1/Grp 2 (range=23.08-48.22 ng/g. w.w. cell pellet). However, a significantly greater time and temperature-dependence was noted for THC in PBMC CLL,Grp 2 compared to PBMC HI Conclusion

Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ9-THC: Mechanism underlying greater toxicity?

Science.gov (United States)

Fantegrossi, William E.; Moran, Jeffery H.; Radominska-Pandya, Anna; Prather, Paul L.

2013-01-01

K2 or Spice products are emerging drugs of abuse that contain synthetic cannabinoids (SCBs). Although assumed by many teens and first time drug users to be a “safe” and “legal” alternative to marijuana, many recent reports indicate that SCBs present in K2 produce toxicity not associated with the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). This mini-review will summarize recent evidence that use of K2 products poses greater health risks relative to marijuana, and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ9-THC may contribute to the observed toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ9-THC typically observed in vitro, SCBs in K2 products act as full cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) agonists in both cellular assays and animal studies. Furthermore, unlike Δ9-THC metabolism, several SCB metabolites retain high affinity for, and exhibit a range of intrinsic activities at, CB1 and CB2Rs. Finally, several reports indicate that although quasi-legal SCBs initially evaded detection and legal consequences, these presumed “advantages” have been limited by new legislation and development of product and human testing capabilities. Collectively, evidence reported in this mini-review suggests that K2 products are neither safe nor legal alternatives to marijuana. Instead, enhanced toxicity of K2 products relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2Rs, highlights the inherent danger that may accompany use of these substances. PMID:24084047

Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ(9)-THC: mechanism underlying greater toxicity?

Science.gov (United States)

Fantegrossi, William E; Moran, Jeffery H; Radominska-Pandya, Anna; Prather, Paul L

2014-02-27

K2 or Spice products are emerging drugs of abuse that contain synthetic cannabinoids (SCBs). Although assumed by many teens and first time drug users to be a "safe" and "legal" alternative to marijuana, many recent reports indicate that SCBs present in K2 produce toxicity not associated with the primary psychoactive component of marijuana, ∆(9)-tetrahydrocannabinol (Δ(9)-THC). This mini-review will summarize recent evidence that use of K2 products poses greater health risks relative to marijuana, and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ(9)-THC may contribute to the observed toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ(9)-THC typically observed in vitro, SCBs in K2 products act as full cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) agonists in both cellular assays and animal studies. Furthermore, unlike Δ(9)-THC metabolism, several SCB metabolites retain high affinity for, and exhibit a range of intrinsic activities at, CB1 and CB2Rs. Finally, several reports indicate that although quasi-legal SCBs initially evaded detection and legal consequences, these presumed "advantages" have been limited by new legislation and development of product and human testing capabilities. Collectively, evidence reported in this mini-review suggests that K2 products are neither safe nor legal alternatives to marijuana. Instead, enhanced toxicity of K2 products relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2Rs, highlights the inherent danger that may accompany use of these substances. © 2013.

Therapeutic Use of Δ9-THC and Cannabidiol: Evaluation of a New Extraction Procedure for the Preparation of Cannabis-based Olive Oil.

Science.gov (United States)

Morini, Luca; Porro, Giorgio; Liso, Maurizio; Groppi, Angelo

2017-01-01

Since 2013 Cannabis-based preparations, containing the two main cannabinoids of interest, Δ9-tetrahydrocannabinol (THC), and cannabidiol (CBD), can be used for therapeutic purposes, such as palliative care, neurodegenerative disorder treatment and other therapies. The preparations may consist of a drug partition in sachets, capsules or through the extraction in certified olive oil. The aims of the study were: a) to develop and validate a new liquid chromatographictandem mass spectrometric (LC-MS/MS) method for the identification and quantification of THC and CBD in olive oil; b) to evaluate the extraction efficiency and reproducibility of a new commercial extractor on the market. The olive oil was simply diluted three consecutive times, using organic solvents with increasing polarity index (n-hexane → isopropanol → methanol). The sample was then directly injected into LC-MS/MS system, operating in Multiple Reaction Monitoring Mode, in positive polarization. The method was then fully validated. The method assessed to be linear over the range 0.1-10 ng/µL for both THC and CBD. Imprecision and accuracy were within 12.2% and 16.9% respectively; matrix effects proved to be negligible; THC concentration in oil is stable up to two months at room temperature, whenever kept in the dark. CBD provided a degradation of 30% within ten weeks. The method was then applied to olive oil after sample preparation, in order to evaluate the efficiency of extraction of a new generation instrument. Temperature of extraction is the most relevant factor to be optimized. Indeed, a difference of 2°C (from 94.5°C to 96.5°C, the highest temperature reached in the experiments) of the heating phase, increases the percentage of extraction from 54.2% to 64.0% for THC and from 58.2% to 67.0% for CBD. The amount of THC acid and CBD acid that are decarboxylated during the procedure must be check out in the future. The developed method was simple and fast. The extraction procedure proved to be

THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

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Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

2018-03-01

Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

Tar, CO and delta 9THC delivery from the 1st and 2nd halves of a marijuana cigarette.

Science.gov (United States)

Tashkin, D P; Gliederer, F; Rose, J; Chang, P; Hui, K K; Yu, J L; Wu, T C

1991-11-01

Previous in vitro studies suggest that, with successive puffs from a marijuana cigarette, delta-9-THC becomes concentrated in the remaining uncombusted portion of the cigarette. These observations are consistent with the common practice of smoking marijuana cigarettes to a smaller butt length than that to which tobacco cigarettes are smoked. The purpose of the present study was to compare the delivery of delta-9-THC, as well as total insoluble smoke particulates (tar) and carbon monoxide, from the distal ("first") versus the proximal ("second") halves of a standard marijuana cigarette during "natural" smoking of marijuana. On 4 separate days, ten habitual marijuana users smoked nearly all or approximately 1/2 of a standard marijuana cigarette (83 mm length; 800-900 mg; 1.24% THC), as follows: day 1, "whole" cigarette (60 mm smoked, leaving a 23-mm butt); day 2, "first" half (first 30 mm); day 3, "second" half (second 30 mm) after the "first" half was presmoked with a syringe; and day 4, "second" half after the "first" half was excised. A previously described smoking apparatus (20) was used for measurement of puff volume and inhaled tar. Puff volume and number were allowed to vary spontaneously (provided that the specified length of cigarette was consumed), while inhaled volume (1.5 liters), breathholding time (14 s) and interpuff interval (30 s) were held constant. Blood samples were withdrawn prior to smoking and serially after completion of smoking for analysis of blood carboxyhemoglobin (COHb) and serum delta-9-THC. Heart rate was measured before and 5 min after smoking. Subjects rated their level of "high" 20 min after completion of smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Significant enhancement of 11-Hydroxy-THC detection by formation of picolinic acid esters and application of liquid chromatography/multi stage mass spectrometry (LC-MS(3) ): Application to hair and oral fluid analysis.

Science.gov (United States)

Thieme, Detlef; Sachs, Ulf; Sachs, Hans; Moore, Christine

2015-07-01

Formation of picolinic acid esters of hydroxylated drugs or their biotransformation products is a promising tool to improve their mass spectrometric ionization efficiency, alter their fragmentation behaviour and enhance sensitivity and specificity of their detection. The procedure was optimized and tested for the detection of cannabinoids, which proved to be most challenging when dealing with alternative specimens, for example hair and oral fluid. In particular, the detection of the THC metabolites hydroxyl-THC and carboxy-THC requires ultimate sensitivity because of their poor incorporation into hair or saliva. Both biotransformation products are widely accepted as incorporation markers to distinguish drug consumption from passive contamination. The derivatization procedure was carried out by adding a mixture of picolinic acid, 4-(dimethylamino)pyridine and 2-methyl-6-nitrobenzoic anhydride in tetrahydrofuran/triethylamine to the dry extraction residues. Resulting derivatives were found to be very stable and could be reconstituted in aqueous or organic buffers and subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). Owing to the complex consecutive fragmentation patterns, the application of multistage MS3 proved to be extremely useful for a sensitive identification of doubly picolinated hydroxy-THC in complex matrices. The detection limits - estimated by comparison of corresponding signal-to-noise ratios - increased by a factor of 100 following picolination. All other species examined, like cannabinol, THC, cannabidiol, and carboxy-THC, could also be derivatized exhibiting only moderate sensitivity improvements. The assay was systematically tested using hair samples and exemplarily applied to oral fluid. Concentrations of OH-THC identified in THC-positive hair samples ranged from 0.02 to 0.29pg/mg. Copyright © 2014 John Wiley & Sons, Ltd.

Δ9-tetrahydrocannabinol (Δ9-THC) administration after neonatal exposure to phencyclidine potentiates schizophrenia-related behavioral phenotypes in mice.

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Rodríguez, Guadalupe; Neugebauer, Nichole M; Yao, Katherine Lan; Meltzer, Herbert Y; Csernansky, John G; Dong, Hongxin

2017-08-01

The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co-morbidity are not well understood. In this study, we examined the effects of Δ9-THC exposure during early adulthood on schizophrenia-related behaviors using a developmental mouse model of schizophrenia. Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10mg/kg). In turn, Δ9-THC or saline was administered sub-acutely later in life to cohorts of animals who had received either PCP or saline (P55-80, 5mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre-pulse inhibition (PPI) task paradigm that were consistent with schizophrenia-related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received Δ9-THC later in life displayed behavioral changes in the locomotor activity paradigm (pschizophrenia-related phenotype, as well as potentiated changes in the NOR (pschizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Part II: Strain- and sex-specific effects of adolescent exposure to THC on adult brain and behaviour: Variants of learning, anxiety and volumetric estimates.

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Keeley, R J; Trow, J; Bye, C; McDonald, R J

2015-07-15

Marijuana is one of the most highly used psychoactive substances in the world, and its use typically begins during adolescence, a period of substantial brain development. Females across species appear to be more susceptible to the long-term consequences of marijuana use. Despite the identification of inherent differences between rat strains including measures of anatomy, genetics and behaviour, no studies to our knowledge have examined the long-term consequences of adolescent exposure to marijuana or its main psychoactive component, Δ(9)-tetrahydrocannabinol (THC), in males and females of two widely used rat strains: Long-Evans hooded (LER) and Wistar (WR) rats. THC was administered for 14 consecutive days following puberty onset, and once they reached adulthood, changes in behaviour and in the volume of associated brain areas were quantified. Rats were assessed in behavioural tests of motor, spatial and contextual learning, and anxiety. Some tasks showed effects of injection, since handled and vehicle groups were included as controls. Performance on all tasks, except motor learning, and the volume of associated brain areas were altered with injection or THC administration, although these effects varied by strain and sex group. Finally, analysis revealed treatment-specific correlations between performance and brain volumes. This study is the first of its kind to directly compare males and females of two rat strains for the long-term consequences of adolescent THC exposure. It highlights the importance of considering strain and identifies certain rat strains as susceptible or resilient to the effects of THC. Copyright © 2015 Elsevier B.V. All rights reserved.

Feasibility study of a vertical slit for the LBS line of the Linac4

CERN Document Server

Ouzia, Alexandre; Maglioni, Cesare; Leitao, Ivo

The feasibility study of a vertical Slit was performed. This Slit is needed for the diagnostic Line for Beam energy Spread of the Linac 4 (LBS line). The Linac 4 will replace the Linac 2 and enable the Large Hadron Collider (LHC) to reach an energy of 14 TeV (highest energy ever reached). When the beam impact on it, the Slit heats up and deforms. The deformation of the slit is the key problem. The present feasibility study aims at assessing whether or not it is feasible to keep this deformation below 50_m, according to the specifications [14]. The determination of all the issues related with the Slit was driven. The priority was given to the thermo-mechanical issues. The methodology chosen to approach the problem led to three steps: -\tFirst, the determination of possible designs for the Slit. One design was identified. -\tSecond, the determination of the best materials. Two figures of merit and a model were specifically conceived for it. Graphite R4550 was identified as the best material. -\tThird, the Monte-Ca...

Beyond THC: the new generation of cannabinoid designer drugs

Directory of Open Access Journals (Sweden)

Liana eFattore

2011-09-01

Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.

Science.gov (United States)

Cherniakov, Irina; Izgelov, Dvora; Domb, Abraham J; Hoffman, Amnon

2017-11-15

The lipophilic phytocannabinoids cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds. Advanced PNLs are PNLs with an incorporated natural absorption enhancers. These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations. Consequently, we have explored the utility of these Advanced-PNLs on CBD and THC oral bioavailability. Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations. The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution. Our Piperine-PNL can be used as a platform for synchronized delivery of piperine and CBD or THC to the enterocyte site. This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of CBD and THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized

Effect profile of paracetamol, Δ9-THC and promethazine using an evoked pain test battery in healthy subjects.

Science.gov (United States)

van Amerongen, G; Siebenga, P; de Kam, M L; Hay, J L; Groeneveld, G J

2018-04-10

A battery of evoked pain tasks (PainCart) was developed to investigate the pharmacodynamic properties of novel analgesics in early-phase clinical research. As part of its clinical validation, compounds with different pharmacological mechanisms of actions are investigated. The aim was to investigate the analgesic effects of classic and nonclassic analgesics compared to a sedating negative control in a randomized placebo-controlled crossover study in 24 healthy volunteers using the PainCart. The PainCart consisted of pain tasks eliciting electrical, pressure, heat, cold and inflammatory pain. Subjective scales for cognitive functioning and psychotomimetic effects were included. Subjects were administered each of the following oral treatments: paracetamol (1000 mg), Δ9-THC (10 mg), promethazine (50 mg) or matching placebo. Pharmacodynamic measurements were performed at baseline and repeated up to 10 h postdose. Paracetamol did not show a significant reduction in pain sensation or subjective cognitive functioning compared to placebo. Promethazine induced a statistically significant reduction in PTT for cold pressor and pressure stimulation. Furthermore, reduced subjective alertness was observed. Δ9-THC showed a statistically significant decrease in PTT for electrical and pressure stimulation. Δ9-THC also demonstrated subjective effects, including changes in alertness and calmness, as well as feeling high and psychotomimetic effects. This study found a decreased pain tolerance due to Δ9-THC and promethazine, or lack thereof, using an evoked pain task battery. Pain thresholds following paracetamol administration remained unchanged, which may be due to insufficient statistical power. We showed that pain thresholds determined using this pain test battery are not driven by sedation. The multimodal battery of evoked pain tasks utilized in this study may play an important role in early-phase clinical drug development. This battery of pain tasks is not sensitive to the

Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC.

Science.gov (United States)

Ménétrey, Annick; Augsburger, Marc; Favrat, Bernard; Pin, Marie A; Rothuizen, Laura E; Appenzeller, Monique; Buclin, Thierry; Mangin, Patrice; Giroud, Christian

2005-01-01

Delta(9)-Tetrahydrocannabinol (THC) is frequently found in the blood of drivers suspected of driving under the influence of cannabis or involved in traffic crashes. The present study used a double-blind crossover design to compare the effects of medium (16.5 mg THC) and high doses (45.7 mg THC) of hemp milk decoctions or of a medium dose of dronabinol (20 mg synthetic THC, Marinol on several skills required for safe driving. Forensic interpretation of cannabinoids blood concentrations were attempted using the models proposed by Daldrup (cannabis influencing factor or CIF) and Huestis and coworkers. First, the time concentration-profiles of THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) (active metabolite of THC), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in whole blood were determined by gas chromatography-mass spectrometry-negative ion chemical ionization. Compared to smoking studies, relatively low concentrations were measured in blood. The highest mean THC concentration (8.4 ng/mL) was achieved 1 h after ingestion of the strongest decoction. Mean maximum 11-OH-THC level (12.3 ng/mL) slightly exceeded that of THC. THCCOOH reached its highest mean concentration (66.2 ng/mL) 2.5-5.5 h after intake. Individual blood levels showed considerable intersubject variability. The willingness to drive was influenced by the importance of the requested task. Under significant cannabinoids influence, the participants refused to drive when they were asked whether they would agree to accomplish several unimportant tasks, (e.g., driving a friend to a party). Most of the participants reported a significant feeling of intoxication and did not appreciate the effects, notably those felt after drinking the strongest decoction. Road sign and tracking testing revealed obvious and statistically significant differences between placebo and treatments. A marked impairment was detected after ingestion of the strongest decoction. A CIF value, which relies on the

Acute psychomotor, memory and subjective effects of MDMA and THC (co-) administration over time in healthy volunteers

NARCIS (Netherlands)

Dumont, G.; Van Hasselt, J.; De Kam, M.; Van Gerven, J.; Touw, D.; Buitelaar, J.; Verkes, R.

Introduction: In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Cannabis (main active compound D9-tetrahydrocannabinol or THC) is frequently co-used with ecstasy (Parrott et al., 2007).

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

Science.gov (United States)

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2016-02-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects

Science.gov (United States)

Russo, Ethan B

2011-01-01

Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL−1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. LINKED ARTICLES

Acute psychomotor, memory and subjective effects of MDMA and THC co-administration over time in healthy volunteers

NARCIS (Netherlands)

Dumont, G.J.H.; Van Hasselt, J.G.C.; De Kam, M.; Van Gerven, J.M.A.; Touw, D.J.; Buitelaar, J.K.; Verkes, R.J.

In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') and cannabis. The aim of the present study was to assess the acute effects of co-administration of MDMA and THC (the main psychoactive compound

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Robin J Keeley

2018-03-01

Full Text Available The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆9-tetrahydrocannabinol (THC to male and female Long-Evans (LER and Wistar (WR rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP. A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

The influence of carbon non-stoichiometry on the electronic properties of thorium monocarbide ThC

Energy Technology Data Exchange (ETDEWEB)

Shein, I.R.; Ivanovskii, A.L. [Institute of Solid State Chemistry, Ural Branch of the Russian Academy of Sciences, Ekaterinburg (Russian Federation)

2010-09-15

The first-principle band structure calculations are employed to examine the influence of carbon non-stoichiometry on the structural and electronic properties of the cubic thorium monocarbide ThC. As a result, the equilibrium geometries, electronic bands, densities of states (DOS), Sommerfeld constants and Pauli paramagnetic susceptibility for ThC{sub 1-x} (where x = 0, 0.25 and 0.50) are obtained and analyzed in comparison with available experimental data. Additionally, the formation energies of carbon vacancies are theoretically estimated for ThC{sub 1-x}. The results obtained indicate that the introduction of carbon vacancies in ThC is accompanied by pronounced DOS changes due to the appearance of novel 'vacancy states' in the near-Fermi region formed by comparable contributions of Th 6d and 5f states. The carbon deficiency strongly affects the structure and stability of thorium carbide. For example, for the hypothetical 'over-deficient' composition ThC{sub 0.50} the initial cubic structure undergoes significant tetragonal distortions. On the contrary, for ThC{sub 0.75} the value of Evf is positive and the cubic structure of this phase is preserved. (authors)

INDOOR LOCALIZATION USING WI-FI BASED FINGERPRINTING AND TRILATERATION TECHIQUES FOR LBS APPLICATIONS

Directory of Open Access Journals (Sweden)

S. Chan

2012-06-01

Full Text Available The past few years have seen wide spread adoption of outdoor positioning services, mainly GPS, being incorporated into everyday devices such as smartphones and tablets. While outdoor positioning has been well received by the public, its indoor counterpart has been mostly limited to private use due to its higher costs and complexity for setting up the proper environment. The objective of this research is to provide an affordable mean for indoor localization using wireless local area network (WLAN Wi-Fi technology. We combined two different Wi-Fi approaches to locate a user. The first method involves the use of matching the pre-recorded received signal strength (RSS from nearby access points (AP, to the data transmitted from the user on the fly. This is commonly known as "fingerprint matching". The second approach is a distance-based trilateration approach using three known AP coordinates detected on the user's device to derive the position. The combination of the two steps enhances the accuracy of the user position in an indoor environment allowing location-based services (LBS such as mobile augmented reality (MAR to be deployed more effectively in the indoor environment. The mapping of the RSS map can also prove useful to IT planning personnel for covering locations with no Wi-Fi coverage (ie. dead spots. The experiments presented in this research helps provide a foundation for the integration of indoor with outdoor positioning to create a seamless transition experience for users.

Lbs Augmented Reality Assistive System for Utilities Infrastructure Management Through Galileo and Egnos

Science.gov (United States)

Stylianidis, E.; Valaria, E.; Smagas, K.; Pagani, A.; Henriques, J.; Garca, A.; Jimeno, E.; Carrillo, I.; Patias, P.; Georgiadis, C.; Kounoudes, A.; Michail, K.

2016-06-01

There is a continuous and increasing demand for solutions, both software and hardware-based, that are able to productively handle underground utilities geospatial data. Innovative approaches that are based on the use of the European GNSS, Galileo and EGNOS, sensor technologies and LBS, are able to monitor, document and manage utility infrastructures' data with an intuitive 3D augmented visualisation and navigation/positioning technology. A software and hardware-based system called LARA, currently under develop- ment through a H2020 co-funded project, aims at meeting that demand. The concept of LARA is to integrate the different innovative components of existing technologies in order to design and develop an integrated navigation/positioning and information system which coordinates GNSS, AR, 3D GIS and geodatabases on a mobile platform for monitoring, documenting and managing utility infrastruc- tures on-site. The LARA system will guide utility field workers to locate the working area by helping them see beneath the ground, rendering the complexity of the 3D models of the underground grid such as water, gas and electricity. The capacity and benefits of LARA are scheduled to be tested in two case studies located in Greece and the United Kingdom with various underground utilities. The paper aspires to present the first results from this initiative. The project leading to this application has received funding from the European GNSS Agency under the European Union's Horizon 2020 research and innovation programme under grant agreement No 641460.

LBS AUGMENTED REALITY ASSISTIVE SYSTEM FOR UTILITIES INFRASTRUCTURE MANAGEMENT THROUGH GALILEO AND EGNOS

Directory of Open Access Journals (Sweden)

E. Stylianidis

2016-06-01

Full Text Available There is a continuous and increasing demand for solutions, both software and hardware-based, that are able to productively handle underground utilities geospatial data. Innovative approaches that are based on the use of the European GNSS, Galileo and EGNOS, sensor technologies and LBS, are able to monitor, document and manage utility infrastructures’ data with an intuitive 3D augmented visualisation and navigation/positioning technology. A software and hardware-based system called LARA, currently under develop- ment through a H2020 co-funded project, aims at meeting that demand. The concept of LARA is to integrate the different innovative components of existing technologies in order to design and develop an integrated navigation/positioning and information system which coordinates GNSS, AR, 3D GIS and geodatabases on a mobile platform for monitoring, documenting and managing utility infrastruc- tures on-site. The LARA system will guide utility field workers to locate the working area by helping them see beneath the ground, rendering the complexity of the 3D models of the underground grid such as water, gas and electricity. The capacity and benefits of LARA are scheduled to be tested in two case studies located in Greece and the United Kingdom with various underground utilities. The paper aspires to present the first results from this initiative. The project leading to this application has received funding from the European GNSS Agency under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 641460.

Indoor Localization Using Wi-Fi Based Fingerprinting and Trilateration Techiques for Lbs Applications

Science.gov (United States)

Chan, S.; Sohn, G.

2012-06-01

The past few years have seen wide spread adoption of outdoor positioning services, mainly GPS, being incorporated into everyday devices such as smartphones and tablets. While outdoor positioning has been well received by the public, its indoor counterpart has been mostly limited to private use due to its higher costs and complexity for setting up the proper environment. The objective of this research is to provide an affordable mean for indoor localization using wireless local area network (WLAN) Wi-Fi technology. We combined two different Wi-Fi approaches to locate a user. The first method involves the use of matching the pre-recorded received signal strength (RSS) from nearby access points (AP), to the data transmitted from the user on the fly. This is commonly known as "fingerprint matching". The second approach is a distance-based trilateration approach using three known AP coordinates detected on the user's device to derive the position. The combination of the two steps enhances the accuracy of the user position in an indoor environment allowing location-based services (LBS) such as mobile augmented reality (MAR) to be deployed more effectively in the indoor environment. The mapping of the RSS map can also prove useful to IT planning personnel for covering locations with no Wi-Fi coverage (ie. dead spots). The experiments presented in this research helps provide a foundation for the integration of indoor with outdoor positioning to create a seamless transition experience for users.

Metabolic patterns of JWH-210, RCS-4, and THC in pig urine elucidated using LC-HR-MS/MS: Do they reflect patterns in humans?

Science.gov (United States)

Schaefer, Nadine; Helfer, Andreas G; Kettner, Mattias; Laschke, Matthias W; Schlote, Julia; Ewald, Andreas H; Meyer, Markus R; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

2017-04-01

The knowledge of pharmacokinetic (PK) properties of synthetic cannabinoids (SCs) is important for interpretation of analytical results found for example in intoxicated individuals. In the absence of human data from controlled studies, animal models elucidating SC PK have to be established. Pigs providing large biofluid sample volumes were tested for prediction of human PK data. In this context, the metabolic fate of two model SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4), was elucidated in addition to Δ 9 -tetrahydrocannabinol (THC). After intravenous administration of the compounds, hourly collected pig urine was analyzed by liquid chromatography-high resolution mass spectrometry. The following pathways were observed: for JWH-210, hydroxylation at the ethyl side chain or pentyl chain and combinations of them followed by glucuronidation; for RCS-4, hydroxylation at the methoxyphenyl moiety or pentyl chain followed by glucuronidation as well as O-demethylation followed by glucuronidation or sulfation; for THC, THC glucuronidation, 11-hydroxylation, followed by carboxylation and glucuronidation. For both SCs, parent compounds could not be detected in urine in contrast to THC. These results were consistent with those obtained from human hepatocyte and/or human case studies. Urinary markers for the consumption of JWH-210 were the glucuronide of the N-hydroxypentyl metabolite (detectable for 3-4 h) and of RCS-4 the glucuronides of the N-hydroxypentyl, hydroxy-methoxyphenyl (detectable for at least 6 h), and the O-demethyl-hydroxy metabolites (detectable for 4 h). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Bond energies of ThO+ and ThC+: A guided ion beam and quantum chemical investigation of the reactions of thorium cation with O2 and CO

Science.gov (United States)

Cox, Richard M.; Citir, Murat; Armentrout, P. B.; Battey, Samuel R.; Peterson, Kirk A.

2016-05-01

Kinetic energy dependent reactions of Th+ with O2 and CO are studied using a guided ion beam tandem mass spectrometer. The formation of ThO+ in the reaction of Th+ with O2 is observed to be exothermic and barrierless with a reaction efficiency at low energies of k/kLGS = 1.21 ± 0.24 similar to the efficiency observed in ion cyclotron resonance experiments. Formation of ThO+ and ThC+ in the reaction of Th+ with CO is endothermic in both cases. The kinetic energy dependent cross sections for formation of these product ions were evaluated to determine 0 K bond dissociation energies (BDEs) of D0(Th+-O) = 8.57 ± 0.14 eV and D0(Th+-C) = 4.82 ± 0.29 eV. The present value of D0 (Th+-O) is within experimental uncertainty of previously reported experimental values, whereas this is the first report of D0 (Th+-C). Both BDEs are observed to be larger than those of their transition metal congeners, TiL+, ZrL+, and HfL+ (L = O and C), believed to be a result of lanthanide contraction. Additionally, the reactions were explored by quantum chemical calculations, including a full Feller-Peterson-Dixon composite approach with correlation contributions up to coupled-cluster singles and doubles with iterative triples and quadruples (CCSDTQ) for ThC, ThC+, ThO, and ThO+, as well as more approximate CCSD with perturbative (triples) [CCSD(T)] calculations where a semi-empirical model was used to estimate spin-orbit energy contributions. Finally, the ThO+ BDE is compared to other actinide (An) oxide cation BDEs and a simple model utilizing An+ promotion energies to the reactive state is used to estimate AnO+ and AnC+ BDEs. For AnO+, this model yields predictions that are typically within experimental uncertainty and performs better than density functional theory calculations presented previously.

Clarifying CB2 Receptor-Dependent and Independent Effects of THC on Human Lung Epithelial Cells

OpenAIRE

Sarafian, Theodore; Montes, Cindy; Harui, Airi; Beedanagari, Sudheer R.; Kiertscher, Sylvia; Stripecke, Renata; Hossepian, Derik; Kitchen, Christina; Kern, Rita; Belperio, John; Roth, Michael D.

2008-01-01

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ9-tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 (Sarafian et al., 2003; Sarafian et al., 2005). The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the typ...

Prenatal Tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat

OpenAIRE

Silva, Lindsay; Zhao, Ning; Popp, Susanna; Dow-Edwards, Diana

2011-01-01

Research suggests that not only is marijuana use prevalent among women of reproductive age, but a significant number of women continue to use marijuana and its derivatives throughout pregnancy. Many studies have shown, in both humans and animals, that marijuana exposure during adolescence and adulthood is detrimental to normal cognition and memory. In this study, we examined the effects of daily intravenous injections of 0.15mg/kg Δ9-tetrahydrocannabinol (THC), given to pregnant dams througho...

Evidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study

NARCIS (Netherlands)

Hell, van H.H.; Bossong, M.G.; Jager, G.; Kristo, G.; Osch, M.J.P.; Zelaya, F.; Kahn, R.S.; Ramsey, N.F.

2011-01-01

The main reason for recreational use of cannabis is the ‘high’, the primary psychotropic effect of ¿9-tetrahydrocannabinol (THC). This psychoactive compound of cannabis induces a range of subjective, physical and mental reactions. The effect on heart rate is pronounced and complicates

Patterns of metal composition and biological condition and their association in male common carp across an environmental contaminant gradient in Lake Mead National Recreation Area, Nevada and Arizona, USA

Science.gov (United States)

Patino, R.; Rosen, Michael R.; Orsak, E.L.; Goodbred, S.L.; May, T.W.; Alvarez, David; Echols, K.R.; Wieser, C.M.; Ruessler, S.; Torres, L.

2012-01-01

There is a contaminant gradient in Lake Mead National Recreation Area (LMNRA) that is partly driven by municipal and industrial runoff and wastewater inputs via Las Vegas Wash (LVW). Adult male common carp (Cyprinus carpio; 10 fish/site) were collected from LVW, Las Vegas Bay (receiving LVW flow), Overton Arm (OA, upstream reference), and Willow Beach (WB, downstream) in March 2008. Discriminant function analysis was used to describe differences in metal concentrations and biological condition of fish collected from the four study sites, and canonical correlation analysis was used to evaluate the association between metal and biological traits. Metal concentrations were determined in whole-body extracts. Of 63 metals screened, those initially used in the statistical analysis were Ag, As, Ba, Cd, Co, Fe, Hg, Pb, Se, Zn. Biological variables analyzed included total length (TL), Fulton's condition factor, gonadosomatic index (GSI), hematocrit (Hct), and plasma estradiol-17?? and 11-ketotestosterone (11kt) concentrations. Analysis of metal composition and biological condition both yielded strong discrimination of fish by site (respective canonical model, p< 0.0001). Compared to OA, pairwise Mahalanobis distances between group means were WB < LVB < LVW for metal concentrations and LVB < WB < LVW for biological traits. Respective primary drivers for these separations were Ag, As, Ba, Hg, Pb, Se and Zn; and TL, GSI, 11kt, and Hct. Canonical correlation analysis using the latter variable sets showed they are significantly associated (p<0.0003); with As, Ba, Hg, and Zn, and TL, 11kt, and Hct being the primary contributors to the association. In conclusion, male carp collected along a contaminant gradient in LMNRA have distinct, collection site-dependent metal and morpho-physiological profiles that are significantly associated with each other. These associations suggest that fish health and reproductive condition (as measured by the biological variables evaluated in this

Variation in the Norwegian gyre and its links to the termohaline circulation (THC).

Science.gov (United States)

Gunnarson, B. E.; Linderholm, H. W.; Wilson, R.; Rydval, M.

2017-12-01

Summer temperature patterns in Scandinavia are partly governed by variations in the North Atlantic drift (being part of the Gulf Stream) causing northern Europe to be warmer than similar latitudes. Observation show that northwestern European climate is strongly link to sea surface temperature (SST) and the ocean circulation (the Norwegian gyre, NG) in the Norwegian Sea. On decadal- multidecadal time scales, there is also positive association with the sub-tropical gyre, but also a weaker (and negative) connection to the sub Polar gyre (SPG) which is linked to the thermohaline circulation (THC). The negative correlations occur only during the April-June and July-September (JAS) seasons, when the ocean mixed layer is shallow in the North Atlantic. A network of Maximum Latewood Density (MXD) tree-ring chronologies from 7 sites in Northern Scandinavia, 1 in central Scotland and 1 in Labrador was used to identifying SST influences on local to regional summer temperatures patterns during 1901-20XX. The sites represent tree growth strongly correlated with mean JAS temperatures (Fennoscandia r > 0.7, Scotland r > 0.6, Labrador r > 0.5). Both the Scotland and Labrador chronologies correlates only with SST from adjacent coastal areas. The Fennoscandian chronologies showed strong and temporally consistent correlations with SST across the NG (r > 0.5), but also positive correlations of the same magnitude across the sub-tropical gyre. In addition, a negative, but weaker, correlation was found over the SPG domain. Climate models (PMIP5) were not able to reproduce the correlation patterns evident in both observations and tree-ring data. The tripolar correlation pattern suggests that North Atlantic SST influences summer temperature variability in Northern Fennoscandia, illustrating the potential for using tree-rings to reconstruct the THC and the heat transport towards the North Atlantic region and atmosphere- ocean interaction back in time.

Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

Energy Technology Data Exchange (ETDEWEB)

Junqueira, Adriana, E-mail: francispacagnelli@unoeste.br [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Cicogna, Antônio Carlos [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Engel, Letícia Estevam; Aldá, Maiara Almeida [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Tomasi, Loreta Casquel de [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Giuffrida, Rogério; Giometti, Inês Cristina [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Freire, Ana Paula Coelho Figueira [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Universidade Estadual Paulista (UNESP), Campus Presidente Prudente, SP (Brazil); Aguiar, Andreo Fernando [Universidade do Norte do Paraná, UNOPAR, Londrina, PR (Brazil); Pacagnelli, Francis Lopes [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil)

2016-01-15

Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca{sup 2+} transport.

A new phase of ThC at high pressure predicted from a first-principles study

Science.gov (United States)

Guo, Yongliang; Qiu, Wujie; Ke, Xuezhi; Huai, Ping; Cheng, Cheng; Han, Han; Ren, Cuilan; Zhu, Zhiyuan

2015-08-01

The phase transition of thorium monocarbide (ThC) at high pressure has been studied by means of density functional theory. Through structure search, a new phase with space group P 4 / nmm has been predicted. The calculated phonons demonstrate that this new phase and the previous B2 phase are dynamically stable as the external pressure is greater than 60 GPa and 120 GPa, respectively. The transformation from B1 to P 4 / nmm is predicted to be a first-order transition, while that from P 4 / nmm to B2 is found to be a second-order transition.

Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

Science.gov (United States)

Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

2015-12-01

These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. Copyright © 2015 Elsevier Ltd. All rights reserved.

∆9-THC intoxication by cannabidiol-enriched cannabis extract in two children with refractory epilepsy: full remission after switching to purified cannabidiol

Directory of Open Access Journals (Sweden)

José Alexandre Crippa

2016-09-01

Full Text Available Animal studies and preliminary clinical trials have shown that cannabidiol-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time. The children presented typical signs of intoxication by ∆9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness after using a cannabidiol-enriched extract. The extract was replaced by the same dose of purified cannabidiol with no ∆9-THC in both cases, which led to improvement in intoxication signs and seizure remission. These cases support pre-clinical and preliminary clinical evidence suggesting that cannabidiol may be effective for some patients with epilepsy. Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.

Trace detection of tetrahydrocannabinol (THC) with a SERS-based capillary platform prepared by the in situ microwave synthesis of AgNPs.

Science.gov (United States)

Yüksel, Sezin; Schwenke, Almut M; Soliveri, Guido; Ardizzone, Silvia; Weber, Karina; Cialla-May, Dana; Hoeppener, Stephanie; Schubert, Ulrich S; Popp, Jürgen

2016-10-05

In the present study, an ultra-sensitive and highly reproducible novel SERS-based capillary platform was developed and utilized for the trace detection of tetrahydrocannabinol (THC). The approach combines the advantages of microwave-assisted nanoparticle synthesis, plasmonics and capillary forces. By employing a microwave-assisted preparation method, glass capillaries were reproducibly coated with silver nanoparticles in a batch fabrication process that required a processing time of 3 min without needing to use any pre-surface modifications or add surfactants. The coated capillaries exhibited an excellent SERS activity with a high reproducibility and enabled the detection of low concentrations of target molecules. At the same time, only a small amount of analyte and a short and simple incubation process was required. The developed platform was applied to the spectroscopic characterization of tetrahydrocannabinol (THC) and its identification at concentration levels down to 1 nM. Thus, a highly efficient detection system for practical applications, e.g., in drug monitoring/detection, is introduced, which can be fabricated at low cost by using microwave-assisted batch synthesis techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Changes on metabolic parameters induced by acute cannabinoid administration (CBD, THC) in a rat experimental model of nutritional vitamin A deficiency

OpenAIRE

El Amrani, Loubna; Porres, Jesus M.; Merzouki, Abderrahmane; Louktibi, Abdelaziz; Aranda, Pilar; Lopez-Jurado, María; Urbano, Gloria

2013-01-01

Introduction: Vitamin A deficiency can result from malnutrition, malabsorption of vitamin A, impaired vitamin metabolism associated with liver disease, or chronic debilitating diseases like HIV infection or cancer. Background & aims: Cannabis administration has been described as a palliative symptom management therapy in such pathological stages. Therefore, this research aimed to study the effects of acute administration of cannabidiol (CBD) or thetrahydrocannabinol (THC) on the levels of ret...

Thermo-hydrological and chemical (THC) modeling to support Field Test Design

Energy Technology Data Exchange (ETDEWEB)

Stauffer, Philip H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Jordan, Amy B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Harp, Dylan Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zyvoloski, George Anthony [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Boukhalfa, Hakim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Caporuscio, Florie Andre [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Miller, Terry Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Robinson, Bruce Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2014-09-30

This report summarizes ongoing efforts to simulate coupled thermal-hydrological-chemical (THC) processes occurring within a hypothetical high-level waste (HLW) repository in bedded salt. The report includes work completed since the last project deliverable, “Coupled model for heat and water transport in a high level waste repository in salt”, a Level 2 milestone submitted to DOE in September 2013 (Stauffer et al., 2013). Since the last deliverable, there have been code updates to improve the integration of the salt module with the pre-existing code and development of quality assurance (QA) tests of constitutive functions and precipitation/dissolution reactions. Simulations of bench-scale experiments, both historical and currently in the planning stages have been performed. Additional simulations have also been performed on the drift-scale model that incorporate new processes, such as an evaporation function to estimate water vapor removal from the crushed salt backfill and isotopic fractionation of water isotopes. Finally, a draft of a journal paper on the importance of clay dehydration on water availability is included as Appendix I.

Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated bu CB1 en CB2 receptor coupled pathways

NARCIS (Netherlands)

Verhoeckx, K.C.M.; Korthout, H.A.A.J.; Meeteren-Kreikamp, van A.P.; Ehlert, K.A.; Wang, M.; Greef, de J.; Rodenburg, R.J.T.; Witkamp, R.F.

2006-01-01

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of ¿9-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa

Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways.

NARCIS (Netherlands)

Verhoeckx, K.C.; Korthout, H.A.; Meeteren-Kreikamp, A.P. van; Ehlert, K.A.; Wang, M.; Greef, J. van der; Rodenburg, R.J.T.; Witkamp, R.F.

2006-01-01

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa

Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways

NARCIS (Netherlands)

Verhoeckx, K.C.M.; Korthout, H.A.A.J.; Meeteren-Kreikamp, A.P. van; Ehlert, K.A.; Wang, M.; Greef, J. van der; Rodenburg, R.J.T.; Witkamp, R.F.

2006-01-01

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Δ9-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa

Effects of various intake valve timings and spark timings on combustion, cyclic THC and NOX emissions during cold start phase with idle operation in CVVT engine

International Nuclear Information System (INIS)

Choi, Kwan Hee; Lee, Hyung Min; Hwang, In Goo; Myung, Cha Lee; Park, Sim Soo

2008-01-01

In a gasoline SI engine, valve events and spark timings put forth a major influence on overall efficiency, fuel economy, and exhaust emissions. Residual gases controlled by the valve overlap can be used to reduce NOx emissions and the spark retardation technique can be used to improve raw THC emissions and catalyst light-off performance during the cold start phase. This paper investigated the behaviors of the engine and its combustion characteristics with various intake valve timings and spark timings during the fast idle condition and cold start. And cyclic THC and NOx emissions were measured at the exhaust port and their formation mechanisms were examined with fast response gas analyzers. As a result, THCs and NOx were reduced by 35% and 23% with optimizing valve overlap and spark advance during the cold transient start phase. Consequently, the valve events and ignition timings were found to significantly affect combustion phenomena and cold-start emissions

Modeling of oxygen incorporation in Th, ThC, and ThN by density functional theory calculations

Science.gov (United States)

Pérez Daroca, D.; Llois, A. M.; Mosca, H. O.

2017-12-01

Oxygen incorporation in nuclear fuel materials is an important issue deserving investigation due to its influence on thermophysical and structural properties. Even if there has been a renewed interest in thorium and thorium compounds in the last years, there is still not much research done on this topic. In this work, we study, by means of density functional theory calculations, the incorporation of oxygen in Th, ThC, and ThN. We analyze the electronic structure finding a characteristic peak to be attributed to oxygen incorporation. We also calculate incorporation and solution energies and obtain migration energies of oxygen through different paths finding that migration through vacancy sites is more energetically favorable than through interstitial ones.

Tuning of superconductivity by Ni substitution into noncentrosymmetric ThC o1 -xN ixC2

Science.gov (United States)

Grant, T. W.; Cigarroa, O. V.; Rosa, P. F. S.; Machado, A. J. S.; Fisk, Z.

2017-07-01

The recently discovered noncentrosymmetric superconductor ThCoC2 was observed to show unusual superconducting behavior with a critical temperature of Tc=2.65 K . Here we investigate the effect of nickel substitution on the superconducting state in ThC o1 -xN ixC2 . Magnetization, resistivity, and heat capacity measurements demonstrate Ni substitution has a dramatic effect with critical temperature increased up to Tc=12.1 K for x =0.4 Ni concentration, which is a rather high transition temperature for a noncentrosymmetric superconductor. In addition, the unusual superconducting characteristics observed in pure ThCoC2 appear to be suppressed or tuned with Ni substitution towards a more conventional fully gapped superconductor.

Interpretation of interseismic deformations and the seismic cycle associated with large subduction earthquakes

Science.gov (United States)

Trubienko, Olga; Fleitout, Luce; Garaud, Jean-Didier; Vigny, Christophe

2013-03-01

The deformations of the overriding and subducting plates during the seismic cycle associated with large subduction earthquakes are modelled using 2D and 3D finite element techniques. A particular emphasis is put on the interseismic velocities and on the impact of the rheology of the asthenosphere. The distance over which the seismic cycle perturbs significantly the velocities depends upon the ratio of the viscosity in the asthenosphere to the period of the seismic cycle and can reach several thousand km for rheological parameters deduced from the first years of deformation after the Aceh earthquake. For a same early postseismic velocity, a Burger rheology of the asthenosphere implies a smaller duration of the postseismic phase and thus smaller interseismic velocities than a Maxwell rheology. A low viscosity wedge (LVW) modifies very significantly the predicted horizontal and vertical motions in the near and middle fields. In particular, with a LVW, the peak in vertical velocity at the end of the cycle is predicted to be no longer above the deep end of the locked section of the fault but further away, above the continentward limit of the LVW. The lateral viscosity variations linked to the presence at depth of the subducting slab affect substantially the results. The north-south interseismic compression predicted by this preliminary 2D model over more than 1500 km within the Sunda block is in good agreement with the pre-2004 velocities with respect to South-China inferred from GPS observations in Thailand, Malaysia and Indonesia. In Japan, before the Tohoku earthquake, the eastern part of northern Honshu was subsiding while the western part was uplifting. This transition from subsidence to uplift so far away from the trench is well fitted by the predictions from our models involving a LVW. Most of the results obtained here in a 2D geometry are shown to provide a good estimate of the displacements for fault segments of finite lateral extent, with a 3D spherical

Sistem Informasi Geografis Asrama Mahasiswa Aceh Berbasis LBS (Location Based Service “Saweue Syedara” Berbasis Android

Directory of Open Access Journals (Sweden)

Alwie Augusra T. A

2015-01-01

Full Text Available Student Dormitory is a desirable place to live for all overseas Aceh students that far from home, Student Dormitory be exclusive if the existence of a dormitory is located very far from the government and from the student's hometown, so the presence of dormitory is felt not exist and far from elegant impression , there are many Aceh students dormitory are not recorded by the Regional Government , that recorded only dormitory under the auspices of the government, when in fact the most dormitory are located under other institutions. Along with the development of, make it even easier people's lives in their daily live. During its development, mobile technology can determine the position of users, find the location you want to target, and provide a route to that location. The use of mobile devices for the Aceh Government, Society, and students in particular is to facilitate them in the course of a visit to Student Dormitory. The geographic information system created using the Java programming language with SDK (Software Development Kit Android and using MySQL and SQLite databases, the system is a client-server. The process of making and development of Geographic Information System using SDLC (Software Development Life Cycle using prototyping life cycle. By using the life cycle of prototyping, the design can be quickly created and tested by users. Users can participate in helping the development of a system to provide feedback on the prototype that has been tried before, so that the system be made better. The result of this application design is the realization of a mobile application that can allow users to find information and search for Aceh Student Dormitory in Java Island, Indonesia. The Geographic Information System uses technology of LBS (Location Based Service, this allows users to find the location of dormitory that wish to visit. This system will be developed on mobile devices using the Android operating system.

Hydrologic impacts of climate change and urbanization in Las Vegas Wash Watershed, Nevada

Science.gov (United States)

In this study, a cell-based model for the Las Vegas Wash (LVW) Watershed in Clark County, Nevada, was developed by combining the traditional hydrologic modeling methods (Thornthwaite’s water balance model and the Soil Conservation Survey’s Curve Number method) with the pixel-base...

Numerical Simulation of Tuff Dissolution and Precipitation Experiments: Validation of Thermal-Hydrologic-Chemical (THC) Coupled-Process Modeling

Science.gov (United States)

Dobson, P. F.; Kneafsey, T. J.

2001-12-01

As part of an ongoing effort to evaluate THC effects on flow in fractured media, we performed a laboratory experiment and numerical simulations to investigate mineral dissolution and precipitation. To replicate mineral dissolution by condensate in fractured tuff, deionized water equilibrated with carbon dioxide was flowed for 1,500 hours through crushed Yucca Mountain tuff at 94° C. The reacted water was collected and sampled for major dissolved species, total alkalinity, electrical conductivity, and pH. The resulting steady-state fluid composition had a total dissolved solids content of about 140 mg/L; silica was the dominant dissolved constituent. A portion of the steady-state reacted water was flowed at 10.8 mL/hr into a 31.7-cm tall, 16.2-cm wide vertically oriented planar fracture with a hydraulic aperture of 31 microns in a block of welded Topopah Spring tuff that was maintained at 80° C at the top and 130° C at the bottom. The fracture began to seal within five days. A 1-D plug-flow model using the TOUGHREACT code developed at Berkeley Lab was used to simulate mineral dissolution, and a 2-D model was developed to simulate the flow of mineralized water through a planar fracture, where boiling conditions led to mineral precipitation. Predicted concentrations of the major dissolved constituents for the tuff dissolution were within a factor of 2 of the measured average steady-state compositions. The fracture-plugging simulations result in the precipitation of amorphous silica at the base of the boiling front, leading to a hundred-fold decrease in fracture permeability in less than 6 days, consistent with the laboratory experiment. These results help validate the use of the TOUGHREACT code for THC modeling of the Yucca Mountain system. The experiment and simulations indicate that boiling and concomitant precipitation of amorphous silica could cause significant reductions in fracture porosity and permeability on a local scale. The TOUGHREACT code will be used

LBS Management Review: Submissions

African Journals Online (AJOL)

Author Guidelines. The Lagos Business School Management Review is published by management professionals for practising managers, without sacrificing academic standards. The Review welcomes articles that enhance knowledge about the process of managing an organisation as well as reflect techniques, trends and ...

Current Trends and Challenges in Location-Based Services

Directory of Open Access Journals (Sweden)

Haosheng Huang

2018-05-01

Full Text Available Location-based services (LBS are a growing area of research. This editorial paper introduces the key research areas within the scientific field of LBS, which consist of positioning, modelling, communication, applications, evaluation, analysis of LBS data, and privacy and ethical issues. After that, 18 original papers are presented, which provide a general picture of recent research activities on LBS, especially related to the research areas of positioning, modelling, applications, and LBS data analysis. This Special Issue together with other recent events and publications concerning LBS show that the scientific field of LBS is rapidly evolving, and that LBS applications have become smarter and more ubiquitous in many aspects of our daily life.

Environmental Assessment: 2005 Base Realignment and Closure Seymour Johnson Air Force Base Goldsboro, North Carolina

Science.gov (United States)

2007-07-01

aquatica), red maple (Acer rubrum), and loblolly pine ( Pinus taeda) are also present. • Coastal Plain Small Stream Swamp: Degraded examples of this...Daily Permit Limit (lbs/hr) Emissions (lbs/hr) (lbs/hr) Emissions (lbs/day) Emissions (lbs/day) (lbs/day) Ethyl Acetate 0 0 481.8 - - -- Methyl Ethyl...Ketone 0.54 1.08 34.1 2.7 5.4 76.2 Methyl Isobutyl Ketone 0.41 0.82 105.6 2.05 4.1 2247.7 Toluene 0.71 1.42 23.8 3.55 7.1 571.4 Xylene 0.33 0.66

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Science.gov (United States)

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Drug-drug interactions as a result of co-administering Δ9-THC and CBD with other psychotropic agents.

Science.gov (United States)

Rong, Carola; Carmona, Nicole E; Lee, Yena L; Ragguett, Renee-Marie; Pan, Zihang; Rosenblat, Joshua D; Subramaniapillai, Mehala; Shekotikhina, Margarita; Almatham, Fahad; Alageel, Asem; Mansur, Rodrigo; Ho, Roger C; McIntyre, Roger S

2018-01-01

To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents. Areas covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper. Expert opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

Strength Testing in the Air Force: Current Processes and Suggestions for Improvements

Science.gov (United States)

2014-01-01

administered at the MEPS (their names are excluded to protect confidentiality ). We also thank the career field managers who participated in our interviews...machine (140–150 lbs) an average, adult, American woman (140–160 lbs) an average, adult, American man (170–190 lbs) an average, freestanding kitchen ...an average, adult, American woman (140–160 lbs) an average, adult, American man (170–190 lbs) an average, freestanding kitchen range and oven

Women in Combat: Issues for Congress

Science.gov (United States)

2016-12-13

Heavy (black) Standing long jump 120 cm 140 cm 160 cm Seated power throw (4.4 lbs medicine ball) 350 cm 400 cm 450 cm Strength deadlift 120 lbs...140 lbs 160 lbs Interval run (20- meter course) 36 shuttles 40 shuttles 43 shuttles 101 Army MEDCOM...30-lbs ammo-can lifts Timed 880- yard sprint Timed 300- yard shuttle run Standard IST 2 (men) 12 second flexed arm hang (women) 1.5 miles in

Secure and privacy-enhancing LBS

OpenAIRE

Jin, Hongyu

2013-01-01

The rapid growth of population and the increasing number of vehicles haveled to high accident rates and cause frequently traffic congestion, especiallyin densely populated countries. There is an urgent need to develop and deployIntelligent Transport Systems (ITSs), in order to improve traffic efficiencyand reduce traffic accidents. The emergence and development of advancedtechnologies lays a good foundation for ITSs; for example, wireless communicationand sensing technologies. To promote the ...

A coupled THC model of the FEBEX in situ test with bentonite swelling and chemical and thermal osmosis

Energy Technology Data Exchange (ETDEWEB)

Zheng, L.; Samper, J.; Montenegro, L.

2011-04-01

The performance assessment of a geological repository for radioactive waste requires quantifying the geochemical evolution of the bentonite engineered barrier. This barrier will be exposed to coupled thermal (T), hydrodynamic (H), mechanical (M) and chemical (C) processes. This paper presents a coupled THC model of the FEBEX (Full-scale Engineered Barrier EXperiment) in situ test which accounts for bentonite swelling and chemical and thermal osmosis. Model results attest the relevance of thermal osmosis and bentonite swelling for the geochemical evolution of the bentonite barrier while chemical osmosis is found to be almost irrelevant. The model has been tested with data collected after the dismantling of heater 1 of the in situ test. The model reproduces reasonably well the measured temperature, relative humidity, water content and inferred geochemical data. However, it fails to mimic the solute concentrations at the heater-bentonite and bentonite-granite interfaces because the model does not account for the volume change of bentonite, the CO{sub 2}(g) degassing and the transport of vapor from the bentonite into the granite. The inferred HCO{sub 3}{sup -} and pH data cannot be explained solely by solute transport, calcite dissolution and protonation/deprotonation by surface complexation, suggesting that such data may be affected also by other reactions.

A coupled THC model of the FEBEX in situ test with bentonite swelling and chemical and thermal osmosis

International Nuclear Information System (INIS)

Zheng, L.; Samper, J.; Montenegro, L.

2011-01-01

The performance assessment of a geological repository for radioactive waste requires quantifying the geochemical evolution of the bentonite engineered barrier. This barrier will be exposed to coupled thermal (T), hydrodynamic (H), mechanical (M) and chemical (C) processes. This paper presents a coupled THC model of the FEBEX (Full-scale Engineered Barrier EXperiment) in situ test which accounts for bentonite swelling and chemical and thermal osmosis. Model results attest the relevance of thermal osmosis and bentonite swelling for the geochemical evolution of the bentonite barrier while chemical osmosis is found to be almost irrelevant. The model has been tested with data collected after the dismantling of heater 1 of the in situ test. The model reproduces reasonably well the measured temperature, relative humidity, water content and inferred geochemical data. However, it fails to mimic the solute concentrations at the heater-bentonite and bentonite-granite interfaces because the model does not account for the volume change of bentonite, the CO 2 (g) degassing and the transport of vapor from the bentonite into the granite. The inferred HCO 3 - and pH data cannot be explained solely by solute transport, calcite dissolution and protonation/deprotonation by surface complexation, suggesting that such data may be affected also by other reactions.

75 FR 14116 - Approval of Implementation Plans of Wisconsin: Nitrogen Oxides Reasonably Available Control...

Science.gov (United States)

2010-03-24

... utility coal fired boilers to account for installation and electric reliability needs. All emission.... Wall-fired (low heat release), 0.15 lbs/mmBtu. Wall-fired (high heat release), 0.17 lbs/mmBtu. Cyclone.../ Tangential-fired, 0.15 lbs/mmBtu. hr. Wall-fired (low heat release), 0.15 lbs/mmBtu. Wall-fired (high heat...

Theory of the axi-symmetric extrusion process of multi-layer materials with a strong plastic nonhomogeneity

Directory of Open Access Journals (Sweden)

J. Piwnik

2008-03-01

Full Text Available A novel simplified r hcorctical solution is found lor thc strcss starcs accompanying thc proccss of cxt ri~siono f ma![ i-laycr matcrialsunder rhc conditions af axial symmetry. Thc solution i~ bawd nn ~ h mc n dcl of pcrfcct plastic material satisfying thc Trcsca yicld condition.thc Haar-Karman conditions bcing sntisficd in each layer. Thc laycrs arc chnnctcrizcd by difrercnt yicld limits and stmng plasticnonhomogeneity. In thc ncighhoi~rhoorol f thc interfaces conrinuous variation of rhc yicld limit i s a~sunicdZ. hc form of thc plastic zonc nndpsitions or the contact surfi~ccss eparating rhc laycrs nrc assumcd. Shcaring strcsscs and mcan prcssurc in a longitudinal scclion o f t hccxrruded rod arc cxprcsscd in tcrms of filnctions of the axial coordinatc z. Unknown fttnctions of thc singlc coordinatc z arc dctcrmincdFrom thc yicld conditions writtcn for thc contour of thc die. Accitratc analytical relations arc dcrivcd For tllc normal strcss distribution atthc surface of contact bctwccn thc dic and thc matcrial cxlrudcd, Using thc known normal and shcar stress dislrihutions (due to Iriclion,accuratc valuc of thc lower cstimate of thc cxtrusion forcc is dctcrrnincd. Thc sotution may hc applicd lo ~ h cca scs of arbitrary numhcr oflaycrs and arbitrary h rm oithc dic. I t may bc used to a rational analysis o f ~ h pcro ccss of cxirnsiol~o f multi-lnycr cylindrical rods.

Development of a simple and sensitive liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) method for the determination of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) and its metabolites in rat whole blood after oral administration of a single high dose of CBD.

Science.gov (United States)

Palazzoli, Federica; Citti, Cinzia; Licata, Manuela; Vilella, Antonietta; Manca, Letizia; Zoli, Michele; Vandelli, Maria Angela; Forni, Flavio; Cannazza, Giuseppe

2018-02-20

The investigation of the possible conversion of cannabidiol (CBD) into Δ 9 -tetrahydrocannabinol (THC) in vivo after oral administration of CBD is reported herein since recent publications suggested a rapid conversion in simulated gastric fluid. To this end, single high dose of CBD (50mg/kg) was administered orally to rats and their blood was collected after 3 and 6h. A highly sensitive and selective LC-MS/MS method was developed and fully validated in compliance with the Scientific Working Group of Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. This method also involved the optimization of cannabinoids and their metabolites extraction in order to remove co-eluting phospholipids and increase the sensitivity of the MS detection. Neither THC nor its metabolites were detected in rat whole blood after 3 or 6h from CBD administration. After oral administration, the amount of CBD dissolved in olive oil was higher than that absorbed from an ethanolic solution. This could be explained by the protection of lipid excipients towards CBD from acidic gastric juice. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of abrasive machining on Fe3AI intermetal surface texture

OpenAIRE

A. Patejuk; M. Poniatowska

2008-01-01

Thc paper prcscnts the results of analyzing thc surfacc tcxtilrc of sarnplcs obtaincd in thc proccss or casting with thc usc of thc Fc7AIintcrmctollic phasc altcr sclccrcd abrasivc machining opt ions havc bccn applicd - milling. wct polishing, l'hc annIysis of ihc surracctcxturc aftcr machining was carricd out by examining such pararnctcrs as: Rn. Rz. RSm. and thc profitc fi~nction- thc lnatcrial ratio curvcand thc nmpli!udc dcnsity cunc.

Theory of the axi-symmetric extrusion process of multi-layer materials with a strong plastic nonhomogeneity

OpenAIRE

J. Piwnik; A. Patejuk

2008-01-01

A novel simplified r hcorctical solution is found lor thc strcss starcs accompanying thc proccss of cxt ri~siono f ma![ i-laycr matcrialsunder rhc conditions af axial symmetry. Thc solution i~ bawd nn ~ h mc n dcl of pcrfcct plastic material satisfying thc Trcsca yicld condition.thc Haar-Karman conditions bcing sntisficd in each layer. Thc laycrs arc chnnctcrizcd by difrercnt yicld limits and stmng plasticnonhomogeneity. In thc ncighhoi~rhoorol f thc interfaces conrinuous variation of rhc yic...

Prices dip along with volume

International Nuclear Information System (INIS)

Anon.

1993-01-01

The summer doldrums took hold in July, with only eight deals taking place, four on the spot concentrates market, two in conversion and two in enrichment. Spot concentrates volume dropped by 23% to nearly 1.2 million lbs U308 equivalent, resulting in slight declines in NUKEM's restricted and unrestricted price ranges. There were four deals on the spot market in July, totaling nearly 1.2 million lbs U3O8 equivalent. One of the buyers, a US utility, bought low-enriched uranium containing up to 440,000 lbs equivalent. Two of the buyers, a European and a US utility, purchased nearly 580,000 lbs of concentrates, with most going to the European utility. And another US utility bought UF6 containing 149,000 lbs equivalent. As for new demand, four buyers - including the European and US utilities that bought concentrates, as well as an East European utility and a non-US producer - entered the market during the month seeking 1.4 million lbs equivalent. The latter two buyers, along with another European utility and another US utility, are now weighing offers for more than 2.2 million lbs U3O8 equivalent. Looking ahead, we anticipate that as many as 17 buyers may enter the market for nearly 5 million lbs equivalent

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments.

Science.gov (United States)

2017-03-23

On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.

Engineering Evaluation Tests of 16 Gauge vs 14 Gauge Staples IAW MIL-STD-1660, 40MM Cartridge on Wooden Pallet

National Research Council Canada - National Science Library

Dugan, Jeffery L

2008-01-01

.... Three test units were tested with a load of 2,290 lbs, 2,295 lbs, and 2,295 lbs. The testing accomplished on the test units was the Stacking, Repetitive Shock, Drop, Incline-Impact, Forklifting, and Disassembly Tests. Test Units #1...

Relationship between Power Factors of Mixer Drive and Selected Technological Parameters

OpenAIRE

R. Wrona; E. Ziółkowski; K. Smyksy

2008-01-01

Thc paper summarizes the selected results of tcsts pcrforrncd to find thc relationship bctwcca thc tcchnological and operational paramctcrsand power consumption by a mixcr drivc. Major tcchnological pammetcrs of moulding sand to considcr arc: mixing lime. moisturecontent. pan load. EIectric power demand is cxprcsscd by crfcctivc valucs, assuming thc bnlanccd tod. Thc propcrtics of moulding sandare shown to be correlated with pwcr factors. As thc mixing lcvcts changc, thc tcchnologicnl pararna...

The privacy concerns in location based services: protection approaches and remaining challenges

OpenAIRE

Basiri, Anahid; Moore, Terry; Hill, Chris

2016-01-01

Despite the growth in the developments of the Location Based Services (LBS) applications, there are still several challenges remaining. One of the most important concerns about LBS, shared by many users and service providers is the privacy. Privacy has been considered as a big threat to the adoption of LBS among many users and consequently to the growth of LBS markets. This paper discusses the privacy concerns associated with location data, and the current privacy protection approaches. It re...

DECOVALEX-THMC Project. Task D. Long-Term Permeability/Porosity Changes in the EDZ and Near Field due to THM and THC Processes in Volcanic and Crystalline-Bentonite Systems. Phase 1 Report

International Nuclear Information System (INIS)

Birkholzer, J.; Rutqvist, J.; Sonnenthal, E.; Barr, D.

2007-02-01

The general goal of this project is to encourage multidisciplinary interactive and cooperative research on modeling coupled processes in geologic formations in support of the performance assessment for underground storage of radioactive waste. Three multi-year project stages of DECOVALEX have been completed in the past decade, mainly focusing on coupled thermal-hydrological-mechanical processes. Currently, a fourth three-year project stage of DECOVALEX is under way, referred to as DECOVALEX-THMC. THMC stands for Thermal, Hydrological, Mechanical, and Chemical processes. The new project stage aims at expanding the traditional geomechanical scope of the previous DECOVALEX project stages by incorporating geochemical processes important for repository performance. The U.S. Department of Energy (DOE) leads Task D of the new DECOVALEX phase, entitled 'Long-term Permeability/Porosity Changes in the EDZ and Near Field due to THC and THM Processes for Volcanic and Crystalline-Bentonite Systems.' In its leadership role for Task D, DOE coordinates and sets the direction for the cooperative research activities of the international research teams engaged in Task D. The research program developed for Task D of DECOVALEX-THMC involves geomechanical and geochemical research areas. THM and THC processes may lead to changes in hydrological properties that are important for performance because the flow processes in the vicinity of emplacement tunnels will be altered from their initial state. Some of these changes can be permanent (irreversible), in which case they persist after the thermal conditions have returned to ambient; i.e., they will affect the entire regulatory compliance period. Geochemical processes also affect the water and gas chemistry close to the waste packages, which are relevant for waste package corrosion, buffer stability, and radionuclide transport. Research teams participating in Task D evaluate long-term THM and THC processes in two generic geologic

DECOVALEX-THMC Project. Task D. Long-Term Permeability/Porosity Changes in the EDZ and Near Field due to THM and THC Processes in Volcanic and Crystalline-Bentonite Systems. Phase 1 Report

Energy Technology Data Exchange (ETDEWEB)

Birkholzer, J.; Rutqvist, J.; Sonnenthal, E. [Lawrence Berkeley National Laboratory, CA (United States); Barr, D. [Office of Repository Development, DOE (United States)

2007-02-15

The general goal of this project is to encourage multidisciplinary interactive and cooperative research on modeling coupled processes in geologic formations in support of the performance assessment for underground storage of radioactive waste. Three multi-year project stages of DECOVALEX have been completed in the past decade, mainly focusing on coupled thermal-hydrological-mechanical processes. Currently, a fourth three-year project stage of DECOVALEX is under way, referred to as DECOVALEX-THMC. THMC stands for Thermal, Hydrological, Mechanical, and Chemical processes. The new project stage aims at expanding the traditional geomechanical scope of the previous DECOVALEX project stages by incorporating geochemical processes important for repository performance. The U.S. Department of Energy (DOE) leads Task D of the new DECOVALEX phase, entitled 'Long-term Permeability/Porosity Changes in the EDZ and Near Field due to THC and THM Processes for Volcanic and Crystalline-Bentonite Systems.' In its leadership role for Task D, DOE coordinates and sets the direction for the cooperative research activities of the international research teams engaged in Task D. The research program developed for Task D of DECOVALEX-THMC involves geomechanical and geochemical research areas. THM and THC processes may lead to changes in hydrological properties that are important for performance because the flow processes in the vicinity of emplacement tunnels will be altered from their initial state. Some of these changes can be permanent (irreversible), in which case they persist after the thermal conditions have returned to ambient; i.e., they will affect the entire regulatory compliance period. Geochemical processes also affect the water and gas chemistry close to the waste packages, which are relevant for waste package corrosion, buffer stability, and radionuclide transport. Research teams participating in Task D evaluate long-term THM and THC processes in two generic geologic

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

Test Report: Assembly and Structural Loading of Army Research Lab’s High Strength Low Alloy - Vanadium (HSLA - V) Bridge

Science.gov (United States)

2010-04-28

34 to 1" drive adapter MHE ============ 15,000 lbs forklift 6,000 lbs. forklift 5,000 pallet truck Two 30,000 lbs. 6’x16’ caster wheeled carts...Suggested modifications to reduce assembly time* ================================================== Use powered torque multipliers to torque bolts

Interaction between physical and psychosocial work risk factors for low back symptoms and its consequences amongst Indonesian coal mining workers.

Science.gov (United States)

Widanarko, Baiduri; Legg, Stephen; Devereux, Jason; Stevenson, Mark

2015-01-01

This study assessed the interaction between physical and psychosocial factors for low back symptoms (LBS) and its consequences (reduced activities and absenteeism) in a developing country. A sample of 1294 Indonesian coal mining workers reported occupational exposures, LBS and its consequences using a self-administered questionnaire. Respondents were placed into one of four combination exposure groups: high physical and high psychosocial (HPhyHPsy); high physical and low psychosocial (HPhyLPsy); low physical and high psychosocial (LPhyHPsy), and; low physical and low psychosocial (LPhyLPsy). The attributable proportion due to interaction between physical and psychosocial factors was examined. Individuals in the HPhyHPsy group were most likely to report LBS (OR 5.42, 95% CI 3.30-8.89), reduced activities (OR 4.89, 95% CI 3.09-7.74), and absenteeism (OR 4.96, 95% CI 3.05-8.06). Interactions between physical and psychosocial factors were present for LBS, reduced activities, and absenteeism; although for LBS and absenteeism the interactions were not significant. Current smokers were more likely to report LBS consequences. Permanent employment and night shift work increased the odds of LBS and its consequences. We conclude that interventions aimed at reducing LBS and its consequences should address both physical and psychosocial factors, with a focus on smokers, permanent employment and night shift work. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Novel method of determination of D9-tetrahydrocannabinol(THC) in human serum by high-performance liquid chromatography with electrochemical detection.

Science.gov (United States)

Kokubun, Hideya; Uezono, Yasuhito; Matoba, Motohiro

2014-04-01

In Europe and the United States, D9-tetrahydrocannabinol(THC, dronabinol), one of the psychoactive constituents of cannabis, has been used for both its anti-emetic and orexigenic effects in cancer patient receiving chemotherapy.However, dronabinol has not yet been launched in the market in Japan.In the future, it is necessary to ascertain the pharmacokinetics of dronabinol in cancer paitient.Therefore, we developed an HPLC procedure using electrochemical detection(ECD)for quan- titation of the concentrations of dronabinol in blood.An eluent of 50mM KH2PO4/CH3CN(9:16)was used as the mobile phase.The column was used the XTerra®RP18, and the voltage of the electrochemical detector in dronabinol was set at 400 mV.As a result, the calibration curve was linear in the range of 10 ng/mL to 100 ng/mL(y=964.85x -3,419, r=0.997).The lower limit of quantification was 0.5 ng/mL(S/N=3).The relative within-runs and between-runs standard deviations for the assay dronabinol were less than 4.7%. The method reported here is superior to previously reported methods in cancer patient.

40 CFR Table 12 to Subpart Wwww of... - Data Requirements for New and Existing Continuous Lamination Lines and Continuous Casting Lines...

Science.gov (United States)

2010-07-01

... Continuous Lamination Lines and Continuous Casting Lines Complying With a Lbs/Ton Organic HAP Emissions Limit... Requirements for New and Existing Continuous Lamination Lines and Continuous Casting Lines Complying With a Lbs... with a lbs/ton organic HAP emissions limit for continuous lamination lines and continuous casting lines...

Treatment response to the RENEW weight loss intervention in schizophrenia: impact of intervention setting.

Science.gov (United States)

Brown, Catana; Goetz, Jeannine; Hamera, Edna; Gajewski, Byron

2014-11-01

Individuals with serious mental illness have high rates of obesity and a need for specialized weight loss intervention programs. This study examines the efficacy of the RENEW weight loss intervention and examines the impact of the intervention setting on outcomes. 136 individuals with serious mental illness from 4 different settings were randomly assigned to receive the RENEW weight loss intervention or a control condition of treatment as usual. The RENEW intervention is a one year program that includes an intensive, maintenance and intermittent supports phase. The intervention group experienced a modest weight loss of 4.8 lbs at 3 months, 4.1 lbs at 6 months and a slight weight gain of 1.5 lbs at 12 months. The control group gained a total of 6.2 lbs at 12 months. However when settings were examined separately the responder sites had a weight loss of 9.4 lbs at 3 months, 10.9 lbs at 6 months and 7 lbs at 12 months. These results suggest that the settings in which individuals receive services may act as a support or hindrance toward response to weight loss interventions. The concept of the obesogenic environment deserves further examination as a factor in the success of weight loss programs. Copyright © 2014 Elsevier B.V. All rights reserved.

DIFFERENCES IN THE KNEE TORQUE BETWEEN HIGH- AND LOW-BAR BACK SQUAT TECHNIQUES. A PILOT STUDY

Directory of Open Access Journals (Sweden)

Janez Logar

2015-01-01

Full Text Available Purpose: The squat is one of the most frequently used exercises in sports training and competitions. There are several squat variations: i the front squat (FS, ii the high-bar back squat (HBS and iii the low-bar back squat (LBS. As the biomechanics of the LBS technique have been studied to a lesser extent, therefore the purpose of this pilot study was to analyze the differences in knee joint net muscle torque between the HBS and LBS. Methods: One healthy male subject (180.0 cm, 76.0 kg, 26 years performed 10 steady paced squats (5 HBS and 5 LBS with additional weight (40.4 kg to a 90° knee angle. Kinematic and kinetic data were gathered using a high-speed camcorder and a force plate, respectively. The maximal and average knee joint net muscle torques (Mmax and Mavg were then calculated via 2-dimensional inverse dynamics. Results: A significantly greater Mavg was observed using the HBS technique as compared to the LBS, both during the entire range of the squat (MavgHBS = 221.6 ± 5.1 Nm, MavgLBS= 203.3 ± 10.2 Nm; p = 0.026 as well as during the eccentric (MavgHBS = 226.0 ± 5.9 Nm, MavgLBS= 202.0 ± 14.0 Nm; p = 0.043 and concentric (MavgHBS = 216.2 ± 3.6 Nm, MavgLBS= 205.0 ± 7.9 Nm; p = 0.021 phase separately. Conclusions: It can be concluded that the lower Mavg during the LBS could be due to the load transfer to the hip joint, most likely because of the greater anterior tilt of the torso, which is a direct response to a lower and more posterior bar placement on the back to finally maintain an unchanged centre of mass. Confirmation of these findings in a larger sample would imply that the LBS could be a more appropriate squat technique when knee joint relief is desired.

GenBank blastx search result: AK062096 [KOME

Lifescience Database Archive (English)

Full Text Available AK062096 001-044-H12 U17130.1 Rhodococcus erythropolis ORF6' gene, partial cds, regulatory protein ThcR (thc...R), cytochrome P-450 (thcB), ORF4, rhodocoxin (thcC), rhodocoxin reductase (thcD) and ORF5 genes, complete cds.|BCT BCT 3e-18 +3 ...

The Coast Artillery Journal. Volume 71, Number 2, 1929

Science.gov (United States)

1929-08-01

Although airplancs had bcen used in the minor Balkan -Wars in thc pcriod just pre- ceding thc ,Yorld \\\\’ar and had becn tcntatiycly fired on by...wedges or pins. Incidcntally all loose pieces arc fastencd to thc caniagc with chains. 1\\. targct moying at thc spced of an airplanc has a widc...rangc of possiblc mancU\\’cr <lUt’jng thc timc of flight of thc projectilc .. \

Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

International Nuclear Information System (INIS)

Monnet-Tschudi, Florianne; Hazekamp, Arno; Perret, Nicolas; Zurich, Marie-Gabrielle; Mangin, Patrice; Giroud, Christian; Honegger, Paul

2008-01-01

Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 μM in single treatment and of 1 μM and 2 μM in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 μM of THC or JWH 015, whereas the expression of TNF-α remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation

Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

Energy Technology Data Exchange (ETDEWEB)

Monnet-Tschudi, Florianne [Department of Physiology, University of Lausanne, 7, rue du Bugnon CH-1005 Lausanne (Switzerland); Hazekamp, Arno [Department of Plant Metabolomics, University of Leiden (Netherlands); Perret, Nicolas; Zurich, Marie-Gabrielle [Department of Physiology, University of Lausanne, 7, rue du Bugnon CH-1005 Lausanne (Switzerland); Mangin, Patrice; Giroud, Christian [Laboratory of Forensic Toxicology and Chemistry, Institute of Legal Medicine, University Hospital Center and University of Lausanne (Switzerland); Honegger, Paul [Department of Physiology, University of Lausanne, 7, rue du Bugnon CH-1005 Lausanne (Switzerland)

2008-04-01

Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 {mu}M in single treatment and of 1 {mu}M and 2 {mu}M in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 {mu}M of THC or JWH 015, whereas the expression of TNF-{alpha} remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

Science.gov (United States)

Ginsburg, Brett C.; Hruba, Lenka; Zaki, Armia; Javors, Martin; McMahon, Lance R.

2014-01-01

Background Recent changes in the legality of cannabis have prompted evaluation of whether blood levels of Δ9-tetrahydrocannabinol (THC) or its metabolites could be used to substantiate impairment, particularly related to behavioral tasks such as driving. However, because marked tolerance develops to behavioral effects of THC, the applicability of a particular threshold of blood THC as an index of impairment in people with different patterns of use remains unclear. Studies relevant to this issue are difficult to accomplish in humans, as prior drug exposure is difficult to control. Methods Here, effects of THC to decrease rectal temperature and operant response rate compared to levels of THC and its metabolites were studied in blood in two groups of monkeys: one received intermittent treatment with THC (0.1 mg/kg i.v.) and another received chronic THC (1 mg/kg/12 h s.c.) for several years. Results In monkeys with intermittent THC exposure, a single dose of THC (3.2 mg/kg s.c.) decreased rectal temperature and response rate. The same dose did not affect response rate or rectal temperature in chronically exposed monkeys, indicative of greater tolerance. In both groups, blood levels of THC peaked 20–60 min post-injection and had a similar half life of elimination, indicating no tolerance to the pharmacokinetics of THC. Notably, in both groups, the behavioral effects of THC were not apparent when blood levels were maximal (20-min post-administration). Conclusion These data indicate that thresholds for blood levels of THC do not provide a consistent index of behavioral impairment across individuals with different patterns of THC exposure. PMID:24703610

WIRELESS TECHNOLOGIES for LOCATION-BASED SERVICES

Directory of Open Access Journals (Sweden)

Dewi Wirastuti

2012-06-01

Full Text Available This paper presents an overview of wireless technologies that support location-based services (LBS. Satellite and cellular networks have exploited their communication infrastructure to offer LBS. The rapid deployment of mobile broadband wireless networks has offered another appealing application area. Key to the realisation of LBS is an efficient and accurate positioning technique with various methods and offering different performance levels. So far, Global Positioning System (GPS has offered the best accuracy at a low cost but it is challenged by poor indoor coverage. With the rapid deployment of broadband wireless access ubiquitously, Mobile WiMAX (Worldwide Interoperability for Microwave Access is seen as a potential positioning option for LBS. Some key features of WiMAX, i.e., broadband benefit, high speed and large coverage area; it will be exploited to provide LBS.

Mechanistic Studies of the Anti-Ulcerogenic Activity and Acute Toxicity Evaluation of Dichlorido-Copper(II-4-(2-5-Bromo-benzylideneaminoethyl Piperazin-1-ium Phenolate Complex against Ethanol-Induced Gastric Injury in Rats

Directory of Open Access Journals (Sweden)

A. Hamid A. Hadi

2011-10-01

Full Text Available The compound dichlorido-copper(II-4-(2-5-bromobenzylideneaminoethyl piperazin-1-ium phenolate (CuLBS was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01. Serum levels of liver enzymes aspartate (AST and alanine transaminases (ALT, pro-inflammatory (IL-6 and TNF-α and anti-inflammatory (IL-10 cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05 protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.

Tetrahydrocannabinols in clinical and forensic toxicology.

Science.gov (United States)

Kochanowski, Maciej; Kała, Maria

2005-01-01

Cannabinoids are the natural constituents of marihuana (cannabis). The main of them are delta9-tetrahydrocannabinol (9THC)--psychoactive agent, cannabinol (CBN) and cannabidiol (CBD). Cannabis is administered either by smoking or orally. 9THC potency and duration of action as well as its and two of its major metabolites concentrations in organism highly depend on the route of administration. A single active dose of 9THC is estimated on 520 mg. 9THC is rapidly metabolised. It is hydroxylated to an active metabolite, I1 -hydroxy-delta9-tetrahydro-cannabinol (11-OH-THC), then oxidised to an inactive 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), which is conjugated with glucuronic acid and predominantly excreted in the urine. The maximum psychological effect persists for 4-6 h after administration despite of very low 9THC blood concentrations. 9THC plasma concentration declined to values of 2-3 ng/ml during 3-4 h after smoking. Such a low concentration of the active compound in human organism create a demand for use of sensitive analytical methods for detection and determination of 9THC and its metabolites. The most effective techniques for 9THC and related compounds determination in biological material are chromatographic ones (gas and liquid) with mass spectrometric detection and different ionization modes. 9THC and its two metabolites (11-OH-THC and THCCOOH) are present in blood and hair, 9THC in saliva, and THCCOOH in urine. 9THC and related compounds are determined in autopsy material, although deaths by overdose of cannabis are exceptionally rare. Fatalities happen most often after intravenous injection of hashish oil. 9THC and its metabolites determination in different biological materials gives the basis for a wide interpretation of analytical results for clinical and forensic toxicology purposes.

The influence of selected elements on mechanical properties of ferritic ductile iron

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M. S. Soiński

2008-03-01

Full Text Available An altcmpi of dcrcrinininp rhc relationship bcrwccn changcs of quantities of clcmcnts in the alloy (such 'as C, Si, Mn. P. S. Cr, Ni. CL~M.g and thc basic mcchanical propcrtics of thc matcrisl (R,, Rp,0,2r As, IIB, KCV has bccn undcstakcn on thc basis of data concerningproduction of fcrritic ductilc iron of thc EN-G1S-400-IRU-LT grndc (according 10 PN-EN 1563 Standard from about 300 hcars. Thccxamincd cast imn has hccn pmduccd by onc of thc domcstic roundrics in thc induction lurnacc of mcdium Srcqucncy. sphcroidizcd hy t hcplunging rncthod and thcn modified hy thc in-strcam rncthod whilc transferring Ihc cnst iron from thc tmumcnt *csscl to ~ h pco uring IadEc.Caaings havc hccn hcnt trcntcd in ordcr to achicvc khc fully fcrritic structure. Thc analysis of ~ h cco llcctcd data has shown that cvcn srnilllchangcs in cantcnt or n scrics afclc~ncnts( fdling within tlrc limits rcquircd For production of thc duciilc iron can lcnd tn t l~cst atisticallysignificant incrcascs or dccrcnscs in mcchanicnl propcrt ics of rcrriric ductilc iron.

LOT A2 Test, THC-modelling of bentonite buffer in a final repository of spent nuclear fuel

International Nuclear Information System (INIS)

Itaelae, A.; Olin, M.; Rasilainen, K.; Pulkkanen, V.M.

2010-01-01

Document available in extended abstract form only. The Finnish spent nuclear fuel disposal is planned to be based on the KBS-3V repository concept. Within this concept, the role of the bentonite buffer is considered to be central. The aim of this study was to model the evolution of the buffer during the thermal phase (heat-generating period of spent fuel), when the bentonite is only partially saturated initially, and the surrounding rock matrix is assumed to be fully saturated. It is essential to study how temperature will affect saturation and also how both of these affect the chemistry of bentonite. In order to make the modeling more concrete, an example experimental case was considered: Long Term Test of Buffer Materials (LOT) A2-parcel test at the Aespoe Hard Rock Laboratory (HRL) in Sweden. In the A2-parcel the MX-80 bentonite was exposed to adverse (120-150 deg. C) temperature conditions and high temperature gradients. The test parcel diameter was smaller than in the actual KBS-3V deposition hole to speed up the saturation. The chemical behaviour of minerals causes their redistribution inside the bentonite. For example, according to the laboratory tests, gypsum dissolves and anhydrite precipitates near the heater-bentonite interface. Also, incoming groundwater affects the bentonite pore water and its properties. These changes may, in turn, influence the mechanical properties of the bentonite. A coupled Thermo-Hydro-Chemical (THC) model was applied, which means that all mechanical effects were ignored. The purpose of the model was first to achieve a satisfactory match between the model and experimental results, and, therefore, the time frame was limited to ten years (LOT A-2 parcel test lasted approximately 6 years). The system was simplified to 1-D in order to reduce the computational work, which can be very significant due to complex chemical calculations. The 1-D model results are reported in Itaelae (2009). The aim is to extend the calculations to 2-D

Utilization of post-reclamation dusts by combustion and oxidising in a pulsating, fluidised bed

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J. Dańko

2008-03-01

Full Text Available Invcaigations of thc urilization process of durn. originated from thc mcchanical scclamatbn of uscd moulding sands with Furfury1 alcohol.werc pcrformcd. Colnbustion and oxidat ion processes of pulvcriscd and scparatetl in cycloncs binding agcnts and othcr organiccomponents wcrc carricd out in thc thcrmal mlairncr wherc a grain hcd ~mdcnvent pulsating fluidisat ion cithcs by thc atmnsphcric air orhy oxypcn cnriched air. Factors dclcrmining an effective pcrlormancc of dusls utilization by oxidising in rhc oxygcn cncichcd air wcreindicated and thc plan for thc Furthcr rcscwch was outlined.

Pharmacokinetics of Cannabinoids

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Iain J McGilveray

2005-01-01

Full Text Available Delta-9-tetrahydrocannabinol (Δ-9-THC is the main psychoactive ingredient of cannabis (marijuana. The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC and nabilone. The variability of THC in plant material (0.3% to 30% leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152±86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively. THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes occurs via the feces and urine. Metabolites persist in the urine and feces for severalweeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h. As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokineticpharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response.

Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study

NARCIS (Netherlands)

van der Pol, P.; Liebregts, N.; Brunt, T.; van Amsterdam, J.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

2014-01-01

Background and Aims Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated

Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study

NARCIS (Netherlands)

van der Pol, Peggy; Liebregts, Nienke; Brunt, Tibor; van Amsterdam, Jan; de Graaf, Ron; Korf, Dirk J.; van den Brink, Wim; van Laar, Margriet

2014-01-01

Increased delta-9-tetrahydrocannabinol (THC) concentrations in cannabis may lead to higher THC exposure, cannabis dependence and treatment need, but users may also adapt the actual intake of THC through reduced inhalation of THC containing smoke (titration). We investigated whether consumers of

Signaling pathway-focused gene expression profiling in pressure overloaded hearts

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Marco Musumeci

2011-01-01

Full Text Available The β-blocker propranolol displays antihypertrophic and antifibrotic properties in the heart subjected to pressure overload. Yet the underlying mechanisms responsible for these important effects remain to be completely understood. The purpose of this study was to determine signaling pathway-focused gene expression profile associated with the antihypertrophic action of propranolol in pressure overloaded hearts. To address this question, a focused real-time PCR array was used to screen left ventricular RNA expression of 84 gene transcripts representative of 18 different signaling pathways in C57BL/6 mice subjected to transverse aortic constriction (TAC or sham surgery. On the surgery day, mice received either propranolol (80 mg/kg/day or vehicle for 14 days. TAC caused a 49% increase in the left ventricular weight-to-body weight (LVW/BW ratio without changing gene expression. Propranolol blunted LVW/BW ratio increase by approximately 50% while causing about a 3-fold increase in the expression of two genes, namely Brca1 and Cdkn2a, belonging to the TGF-beta and estrogen pathways, respectively. In conclusion, after 2 weeks of pressure overload, TAC hearts show a gene expression profile superimposable to that of sham hearts. Conversely, propranolol treatment is associated with an increased expression of genes which negatively regulate cell cycle progression. It remains to be established whether a mechanistic link between gene expression changes and the antihypertrophic action of propranolol occurs.

Disposition of smoked cannabis with high [Delta]9-tetrahydrocannabinol content: A kinetic model.

NARCIS (Netherlands)

Hunault, C.C.; van Eijkeren, J.C.; Mensinga, T.T.; de Vries, I.; Leenders, M.E.C.; Meulenbelt, J.

2010-01-01

Introduction No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose. We aimed to develop a kinetic model providing estimates of the THC serum concentrations after smoking cannabis cigarettes containing high THC doses (up to 69 mg THC).Methods

CARCASS AND MEAT QUALITY OF AFRICANDER Ar{D TERSEY ...

African Journals Online (AJOL)

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Proposed Optimal Fluoroscopic Targets for Cooled Radiofrequency Neurotomy of the Sacral Lateral Branches to Improve Clinical Outcomes: An Anatomical Study.

Science.gov (United States)

Stout, Alison; Dreyfuss, Paul; Swain, Nathan; Roberts, Shannon; Loh, Eldon; Agur, Anne

2017-11-23

Current sacroiliac joint (SIJ) cooled radiofrequency (RF) is based on fluoroscopic anatomy of lateral branches (LBs) in three specimens. Recent studies confirm significant variation in LB positions. To determine if common fluoroscopic needle placements for cooled SIJ RF are adequate to lesion all S1-3 LBs. If not, would different targets improve lesion accuracy? The LBs of 20 cadavers were dissected bilaterally (40 SIJs), and 26 G radiopaque wires were sutured to the LBs. With a 10-mm radius ruler centered at each foramen, standard targets were assessed, as judged by a clockface on the right, for S1 and S2 at 2:30, 4:00, and 5:30 positions and at S3 at 2:30 and 4:00. Mirror image targets were assessed on the left. Assuming an 8-mm lesion diameter, the percentage of LBs that would not be ablated for each level was determined. Imaging through the superior end plate of S1 was compared against segment specific (SS) imaging. Nine point four percent of LBs would not be ablated at S1 vs 0.99% at S2 vs 35% at S3, and 60% of the 40 SIJs would be completely denervated using current targets. SS imaging did not improve results. Alternate target locations could improve the miss rate to 2.8% at S1 and 0% at S3 and would ablate all LBs in 95% of SIJs. Using a conservative 8-mm lesion measurement, contemporary cooled RF needle targets are inadequate to lesion all target LBs. Modifications to current targets are recommended to increase the effectiveness of the procedure. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.

Science.gov (United States)

De Petrocellis, Luciano; Ligresti, Alessia; Schiano Moriello, Aniello; Iappelli, Mariagrazia; Verde, Roberta; Stott, Colin G; Cristino, Luigia; Orlando, Pierangelo; Di Marzo, Vincenzo

2013-01-01

Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than Δ(9) -tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. We tested pure cannabinoids and extracts from Cannabis strains enriched in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU-145 cells. Cannabidiol (CBD) significantly inhibited cell viability. Other compounds became effective in cells deprived of serum for 24 h. Several BDS were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca(2+)). In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis. These data support the clinical testing of CBD against prostate carcinoma. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Ocular disposition of the hemiglutarate ester prodrug of ∆⁹-Tetrahydrocannabinol from various ophthalmic formulations.

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Hingorani, Tushar; Adelli, Goutham R; Punyamurthula, Nagendra; Gul, Waseem; Elsohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

2013-08-01

The overall goal of this project is to enhance ocular delivery of ∆(9)-Tetrahydrocannabinol (THC) through the topical route. Solubility, stability and in vitro transcorneal permeability of the relatively hydrophilic hemiglutarate ester derivative, THC-HG, was studied in the presence of surfactants. The solutions were characterized with respect to micelle size, zeta potential and solution viscosity. In vivo studies were carried out in New Zealand albino rabbits. A previously reported promising THC-HG ion-pair formulation was also studied in vivo. Aqueous solubility and stability and in vitro transcorneal permeability of THC-HG was enhanced significantly in the presence of surfactants. THC levels in the ocular tissues (except cornea) were found to be below detection limits from mineral oil, surfactant or emulsion based formulations containing THC. In contrast, micellar and ion pair based THC-HG formulations produced significantly higher total THC concentrations in the anterior ocular chamber. In this study, although delivery of THC to the anterior chamber ocular tissues could be significantly increased through the prodrug and formulation approaches tested, further studies are needed to increase penetration to the back-of-the eye.

Bounding estimate of DWPF mercury emissions

International Nuclear Information System (INIS)

Jacobs, R.A.

1992-01-01

Purges required for H2 flammability control and verification of elevated Formic Acid Vent Condenser (FAVC) exit temperatures due to NO x reactions have lead to significant changes in Chemical Process Cell (CPC) operating conditions. Accordingly, mercury emissions estimates have been updated based upon the new operating requirements, IDMS (Integrated DWPF Melter System) experience, and development of an NO x /FAVC model which predicts FAVC exit temperatures. Using very conservative assumptions and maximum purge rates, the maximum calculated Hg emissions is approximately 130 lbs/yr. A range of 100 to 120 lbs/yr is conservatively predicted for other operating conditions. Defense Waste Processing Facility (DWPF) permitted Hg emissions are 175 lbs/yr (0.02 lbs/hr annual average)

Plasma and urine profiles of Delta9-tetrahydrocannabinol and its metabolites 11-hydroxy-Delta9-tetrahydrocannabinol and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes.

Science.gov (United States)

Brenneisen, Rudolf; Meyer, Pascale; Chtioui, Haithem; Saugy, Martial; Kamber, Matthias

2010-04-01

Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing

Polymer price hikes meet mixed results

International Nuclear Information System (INIS)

Coeyman, M.

1993-01-01

Quantum's announcement that it will temporarily shut down 150 million lbs/year of high-density polyethylene (HDPE) capacity at its Clinton, IA plant did little to lift spirits among fellow producers. There's still a lot of capacity out there - and a lot more due to come on, say one. Many agree with Charles Neivert, president of New Vernon Associates (Morristown, NJ), who sums up the cutback in three words: Not nearly enough. Despite the loss of 250 million-275 million lbs/year of HDPE capacity last year when OxyChem shut down its Orange, TX plant, and an additional 400 million lbs/year during the month of December when Solvay took equipment down for maintenance at Deer Park, TX, the market is still awash in capacity. In addition, Phillips is planning to bring 600 million lbs/year online late this year, while Formosa is scheduled to add 500 million lbs/year and Himont 200 million lbs/year, both in 1994. HDPE producers have been trying for a price increase since August but so far have not succeeded. The polypropylene market looks much the same. Low-density PE, however is quite another story. Although the 2-cts/lb price initiative on Jan. 1 failed, a Feb. 1 increase seems likely to stick

Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

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Adena S Spiro

Full Text Available The ABC transporters P-glycoprotein (P-gp, Abcb1 and breast cancer resistance protein (Bcrp, Abcg2 regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9-tetrahydrocannabinol (THC has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT mice. Abcb1a/b (-/-, Abcg2 (-/- and wild-type (WT mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/- and Abcg2 (-/- mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/- mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.

Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects.

Science.gov (United States)

Eichler, Martin; Spinedi, Luca; Unfer-Grauwiler, Sandra; Bodmer, Michael; Surber, Christian; Luedi, Markus; Drewe, Juergen

2012-05-01

The most important psychoactive constituent of CANNABIS SATIVA L. is Δ (9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. SATIVA, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. SATIVA extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC (24 h) than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC (24 h) was higher for the heated than for the unheated extract. The median CBD plasma AUC (24 h) was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability. © Georg Thieme Verlag KG Stuttgart · New York.

Disposition of smoked cannabis with high Δ9-tetrahydrocannabinol content: A kinetic model

International Nuclear Information System (INIS)

Hunault, Claudine C.; Eijkeren, Jan C.H. van; Mensinga, Tjeert T.; Vries, Irma de; Leenders, Marianne E.C.; Meulenbelt, Jan

2010-01-01

Introduction: No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose. We aimed to develop a kinetic model providing estimates of the THC serum concentrations after smoking cannabis cigarettes containing high THC doses (up to 69 mg THC). Methods: Twenty-four male non-daily cannabis users smoked cannabis cigarettes containing 29.3 mg, 49.1 mg, and 69.4 mg THC. Blood samples were collected over a period of 0-8 h and serum THC concentrations were measured. A two-compartment open model was fitted on the individual observed data. Results: Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were C max = 175 ng/mL, T max = 14 min, and AUC 0-8h = 8150 ng x min/mL for the 69.4 mg THC dose. Median model results show an almost linear dose response relation for C max /Dose = 2.8 x 10 -6 /mL and AUC 0-8h /Dose = 136 x 10 -6 min/mL. However, for increasing dose level, there was a clear decreasing trend: C max /Dose = 3.4, 2.6 and 2.5 x 10 -6 /mL and AUC 0-8h /Dose = 157, 133 and 117 x 10 -6 min/mL for the 29.3, 49.1 and 69.4 mg dose, respectively. Within the restriction of 8 h of observation, the apparent terminal half life of THC was 150 min. Conclusion: The model offers insight into the pharmacokinetics of THC in recreational cannabis users smoking cannabis containing high doses of THC mixed with tobacco. The model is an objective method for providing serum THC concentrations up to 8 h after smoking cannabis with a high THC content (up to 23%).

A study investigating the acute dose-response effects of 13 mg and 17 mg Delta 9- tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana.

Science.gov (United States)

Weinstein, A; Brickner, O; Lerman, H; Greemland, M; Bloch, M; Lester, H; Chisin, R; Sarne, Y; Mechoulam, R; Bar-Hamburger, R; Freedman, N; Even-Sapir, E

2008-06-01

Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.

Frequency and irregularity of heart rate in drivers suspected of driving under the influence of cannabis.

Science.gov (United States)

Khiabani, Hassan Z; Mørland, Jørg; Bramness, Jørgen G

2008-12-01

Delta 9-tetrahydrocannabinol (THC) is the major active component of cannabis. Cardiovascular effects of THC have previously been reported: tachycardia after intake, but also bradycardia at higher doses. The purpose of this study was, firstly, to investigate the frequency and irregularity of heart rate in a group of cannabis users in their natural surroundings. We also compared THC-positive drivers with a regular pulse with THC-positive drivers with an irregular pulse. The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyzes blood samples from all drivers suspected of driving under the influence of drugs. We studied pulse rate and regularity in 502 THC-positive drivers who tested negative for other substances. As a control group, we randomly selected 125 drug-negative cases from the database of the DFTDA; no alcohol, narcotics, or medicinal drugs of abuse were detected. The Delta9-THC-positive drivers had a higher mean pulse rate than the control group [82.8 beats/min (SD 16.3) versus 75.6 beats/min (SD 9.2)] and more cases with tachycardia were detected in the Delta9-THC-positive group (19.4% versus 1.6%). There was only one driver with an irregular heart beat in the control group, while there were nine among the Delta9-THC-positive drivers. The drivers with an irregular pulse were over-represented amongst those with the lowest blood Delta9-THC concentrations. This report represents a large study of subjects in a real-life situation and includes observations on pulse frequency, regularity, and blood Delta9-THC concentration. A substantial fraction of Delta9-THC-positive drivers had tachycardia, but there was no correlation between blood Delta9-THC concentration and pulse rate in the present study. We had no further diagnostic information on the cause of the pulse irregularities, but our results indicate that occasional users of cannabis tend to have irregular heart rates at low THC concentrations and at low

Truthfulness in Financial Reporting | Elegido | LBS Management ...

African Journals Online (AJOL)

doi.org/10.4314/lbsmr.v4i1.24467 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER ...

Managing youe organisation's ethical climate | Ike | LBS ...

African Journals Online (AJOL)

This article explains how the level of ethical practice in an organisation can be influenced by the core values of the organisation and its internal and external environment. The argues that to ensure high ethical standards in an organisation, it is important to clarify and reinforce core values, and to ensure that the ...

Cannabidiol Does Not Convert to Δ9-Tetrahydrocannabinol in an In Vivo Animal Model.

Science.gov (United States)

Wray, Louise; Stott, Colin; Jones, Nicholas; Wright, Stephen

2017-01-01

Introduction: Cannabidiol (CBD) can convert to Δ 9 -tetrahydrocannabinol (THC) in vitro with prolonged exposure to simulated gastric fluid; however, in vitro conditions may not be representative of the in vivo gut environment. Using the minipig, we investigated whether enteral CBD converts to THC in vivo . Materials and Methods: Synthetic CBD (100 mg/mL) was administered orally in a sesame oil formulation twice daily to minipigs ( N =3) in 15 mg/kg doses for 5 consecutive days. Blood samples were taken before and 1, 2, 4, and 6 h after morning doses on Days 1 and 5. Six hours after the final dose on Day 5, the animals were euthanized, and samples of gastrointestinal (GI) tract contents were obtained. Liquid chromatography with tandem mass spectrometry analysis determined CBD, THC, and 11-hydroxy-THC (11-OH-THC) concentrations. Lower limits of quantification: plasma CBD=1 ng/mL, plasma THC and 11-OH-THC=0.5 ng/mL, GI tract CBD=2 ng/mL, and GI tract THC and 11-OH-THC=1 ng/mL. Results: THC and 11-OH-THC were undetectable in all plasma samples. Maximum plasma concentrations ( C max ) of CBD were observed between 1 and 4 h on Days 1 and 5. CBD was present in plasma 6 h after administration on Days 1 (mean 33.6 ng/mL) and 5 (mean 98.8 ng/mL). Mean C max CBD values, 328 ng/mL (Day 1) and 259 ng/mL (Day 5), were within range of those achieved in clinical studies. Mean CBD exposure over 6 h was similar on Days 1 (921 h·ng/mL) and 5 (881 h·ng/mL). THC and 11-OH-THC were not detected in all GI tract samples. Mean CBD concentrations reached 84,500 ng/mL in the stomach and 43,900 ng/mL in the small intestine. Conclusions: Findings of the present study show that orally dosed CBD, yielding clinically relevant plasma exposures, does not convert to THC in the minipig, a species predictive of human GI tract function.

Pilot investigation - Nominal crew induced forces in zero-g

Science.gov (United States)

Klute, Glenn K.

1992-01-01

This report presents pilot-study data of test subject forces induced by intravehicular activities such as push-offs and landings with both hands and feet. Five subjects participated in this investigation. Three orthogonal force axes were measured in the NASA KC-135 research aircraft's 'zero-g' environment. The largest forces were induced during vertical foot push-offs, including one of 534 newtons (120 lbs). The mean vertical foot push-off was 311 newtons (70 lbs). The vertical hand push-off forces were also relatively large, including one of 267 newtons (60 lbs) with a mean of 151 newtons (34 lbs). These force magnitudes of these forces would result in a Shuttle gravity environment of about 1 x exp 10 -4 g's.

A privacy-preserving framework for outsourcing location-based services to the cloud

OpenAIRE

Zhu, Xiaojie; Ayday, Erman; Vitenberg, Roman

2018-01-01

Thanks to the popularity of mobile devices a large number of location-based services (LBS) have emerged. While a large number of privacy-preserving solutions for LBS have been proposed, most of these solutions do not consider the fact that LBS are typically cloud-based nowadays. Outsourcing data and computation to the cloud raises a number of significant challenges related to data confidentiality, user identity and query privacy, fine-grain access control, and query expressiveness. In this wo...

Location Based Services and Applications

OpenAIRE

Elenis Gorrita Michel; Rónier Sierra Dávila; Samuel Montejo Sánchez

2012-01-01

Location Based Services (LBS) continue to grow in popularity, effectiveness and reliability, to the extent that applications are designed and implemented taking into account the facilities of the user location information. In this work, some of the main applications are addressed, in order to make an assessment of the current importance of the LBS, as a branch of technology in full swing. In addition, the main techniques for location estimation are studied, essential information to the LBS. B...

Commodity chemical growth to slow in 1993

International Nuclear Information System (INIS)

Plishner, E.S.

1992-01-01

In their latest chemical outlook, DRI/McGraw-Hill economists characterize 1992 as a peak year for U.S. commodity chemical demand growth, at 4.2%, tapering off to a compound 2.2% between 1993 and 1995. Just as operating rates begin to reach higher levels in 1995, however, DRI forecasts slowing GNP growth. DRI's Ramunas J. Svarcas expects a decline in exports. Those plastics promising the rosiest consumption outlook include melamine-formaldehyde resin, up 9.9% in 1992, from 155 million lbs in 1991, and projected to grow 8.6%/year through 1995; styrene acrylonitrile resin, up 23% this year, from 58 million lbs last year, and growing 8.2%/year through 1995; and unsaturated polyester, up 11.7% this year, from 1.07 billion lbs in 1991, and increasing at 6.5%/year. Methanol is a bright spot, with consumption growing 4.7%, from 11.2 billion lbs in 1991 and 12%/year thereafter. Ortho-xylene managed an impressive 21% rebound from a depressed 1991 level of 783 million lbs, and is expected to continue its recovery at 7.7%/year

Protection against Mitochondrial and Metal Toxicity Depends on Functional Lipid Binding Sites in ATP13A2

Directory of Open Access Journals (Sweden)

Shaun Martin

2016-01-01

Full Text Available The late endo-/lysosomal P-type ATPase ATP13A2 (PARK9 is implicated in Parkinson’s disease (PD and Kufor-Rakeb syndrome, early-onset atypical Parkinsonism. ATP13A2 interacts at the N-terminus with the signaling lipids phosphatidic acid (PA and phosphatidylinositol (3,5 bisphosphate (PI(3,5P2, which modulate ATP13A2 activity under cellular stress conditions. Here, we analyzed stable human SHSY5Y cell lines overexpressing wild-type (WT or ATP13A2 mutants in which three N-terminal lipid binding sites (LBS1–3 were mutated. We explored the regulatory role of LBS1–3 in the cellular protection by ATP13A2 against mitochondrial stress induced by rotenone and found that the LBS2-3 mutants displayed an abrogated protective effect. Moreover, in contrast to WT, the LBS2 and LBS3 mutants responded poorly to pharmacological inhibition of, respectively, PI(3,5P2 and PA formation. We further demonstrate that PA and PI(3,5P2 are also required for the ATP13A2-mediated protection against the toxic metals Mn2+, Zn2+, and Fe3+, suggesting a general lipid-dependent activation mechanism of ATP13A2 in various PD-related stress conditions. Our results indicate that the ATP13A2-mediated protection requires binding of PI(3,5P2 to LBS2 and PA to LBS3. Thus, targeting the N-terminal lipid binding sites of ATP13A2 might offer a therapeutic approach to reduce cellular toxicity of various PD insults including mitochondrial stress.

Probiotic Mixture Golden Bifido Prevents Neonatal Escherichia coli K1 Translocation via Enhancing Intestinal Defense

Directory of Open Access Journals (Sweden)

Qing Zeng

2017-09-01

Full Text Available Escherichia coli (E. coli K1 sepsis and meningitis is a severe infection characterized by high mortality in neonates. Successful colonization and translocation across the intestinal mucosa have been regarded as the critical steps for E. coli K1 sepsis and meningitis. We recently reported that the probiotic mixture, Golden Bifido (containing live Lactobacillus bulgaricus, Bifidobacterium, and Streptococcus thermophilus, LBS has a preventive role against neonatal E. coli K1 bacteremia and meningitis. However, the interaction between the neonatal gut barrier, probiotics and E. coli K1 is still not elucidated. The present study aims to investigate how LBS exerts its protective effects on neonatal gut barrier during E. coli K1 infection. The beneficial effects of LBS were explored in vitro and in vivo using human colon carcinoma cell lines HT-29 and rat model of neonatal E. coli K1 infection, respectively. Our results showed that stimulation with E. coli K1 was able to cause intestinal barrier dysfunction, which were reflected by E. coli K1-induced intestinal damage and apoptosis of intestinal epithelial cells, reduction of mucin, immunoglobulin A (IgA and tight junction proteins expression, as well as increase in intestinal permeability, all these changes facilitate E. coli K1 intestinal translocation. However, these changes were alleviated when HT-29 cells were treated with LBS before E. coli K1 infection. Furthermore, we found that LBS-treated neonatal rats (without E. coli K1 infection have showed higher production of mucin, ZO-1, IgA, Ki67 in intestinal mucosa as well as lower intestinal permeability than that of non-treated rats, indicating that LBS could accelerate the development of neonatal intestinal defense. Taken together, our results suggest that enhancement of the neonatal intestinal defense to fight against E. coli K1 translocation could be the potential mechanism to elucidate how LBS confers a protective effect against neonatal E

Application of cast nickel alloys for parts of electronics characterised by special magnetic properties

Directory of Open Access Journals (Sweden)

W. UhI

2008-03-01

Full Text Available Thc thcorctical part of the study highlights thc origin of thc idca 10 start investigations on alloys of high ~nngnctic pcrmcability.manufactured mainly by cornpanics in ~ h Uc S A and Japan.'Phc said materials arc applicd for various pans of ctcctronics uscd by thc military industry. c.g. sntctlitc antcnnas Tor globalcommunication with suhmarincs. and for rcscarch instmrncnts, c,g. fcrromagnctic corcs. Thcy arc chnr:~clcriscd by vcry high lnnpncticpcrrncability. resistivity and corrosion rcsistancc which makc thcm suitablc for opcrat ion undcr cxtrn-~ryingc onditions.Nickel alloys of high magnctic propcrtics arc usuall y manufactured as roZlcd products. The amhition of t hc authors or this srlldy is Inmanufacture !hem as cast prnducts.Thc pmgram of rcscarch incIudcd characteristic of nickcl alloys wirh ddi t i ons of molybdcnum slid iron sn~isryingt hc ahnvc mc~iito ncdrcquircmcnu. with attcn~ionf ocusscd on thcir application for magnctic parts of satcllitc antcnnns and fcrromngnctic corcs.Moulding and casting tcchnologics wcrc proposcd to bcst suit ~ h pcr occss OF maaufacturc of r hcsc clcmcnrs.Thc rangc of chcmicaI cornpostion was sclcctcd 20 cnsurc thc rcquircd magnctic. mcchnnicnl and anti-corrosive pmpcrtics.A scrics of melts was prcparcd and castings of thc abovc mcnlioncd clclncn1s wcrc mndc. Thc chclnicnl composi~ioii of IEIC alloys wasanalyscd along with thc stnlcturc cxarninations nnd quality asscssmcnt rnadc by ~ h cno n-dcsrructi vc rncthods, Casrings wcrc sitbjcctcd tothc finishing trcatmcnt, followed by tests and cxamina~ionsto cnablc thcir practical application.

Disposition of smoked cannabis with high {Delta}{sup 9}-tetrahydrocannabinol content: A kinetic model

Energy Technology Data Exchange (ETDEWEB)

Hunault, Claudine C., E-mail: claudine.hunault@rivm.n [National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven (Netherlands); Eijkeren, Jan C.H. van [Expertise Center for Methodology and Information Services, National Institute for Public Health and the Environment, Bilthoven (Netherlands); Mensinga, Tjeert T [National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven (Netherlands); Clinic for treatment of drug addiction in Northern, Vondellaan 71-73, 9721 LB, Groningen (Netherlands); Vries, Irma de [National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven (Netherlands); Leenders, Marianne E.C. [National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven (Netherlands); Division of Perioperative and Emergency Care, University Medical Center Utrecht, 3584 CX (Netherlands); Meulenbelt, Jan [National Poisons Information Center, National Institute for Public Health and the Environment, Bilthoven (Netherlands); Division Intensive Care Center, University Medical Center Utrecht, 3584 CX, Utrecht (Netherlands); Institute for Risk Assessment Sciences, Utrecht University, Utrecht (Netherlands)

2010-08-01

Introduction: No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose. We aimed to develop a kinetic model providing estimates of the THC serum concentrations after smoking cannabis cigarettes containing high THC doses (up to 69 mg THC). Methods: Twenty-four male non-daily cannabis users smoked cannabis cigarettes containing 29.3 mg, 49.1 mg, and 69.4 mg THC. Blood samples were collected over a period of 0-8 h and serum THC concentrations were measured. A two-compartment open model was fitted on the individual observed data. Results: Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were C{sub max} = 175 ng/mL, T{sub max} = 14 min, and AUC{sub 0-8h} = 8150 ng x min/mL for the 69.4 mg THC dose. Median model results show an almost linear dose response relation for C{sub max}/Dose = 2.8 x 10{sup -6}/mL and AUC{sub 0-8h}/Dose = 136 x 10{sup -6} min/mL. However, for increasing dose level, there was a clear decreasing trend: C{sub max}/Dose = 3.4, 2.6 and 2.5 x 10{sup -6}/mL and AUC{sub 0-8h}/Dose = 157, 133 and 117 x 10{sup -6} min/mL for the 29.3, 49.1 and 69.4 mg dose, respectively. Within the restriction of 8 h of observation, the apparent terminal half life of THC was 150 min. Conclusion: The model offers insight into the pharmacokinetics of THC in recreational cannabis users smoking cannabis containing high doses of THC mixed with tobacco. The model is an objective method for providing serum THC concentrations up to 8 h after smoking cannabis with a high THC content (up to 23%).

Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation.

Science.gov (United States)

Sido, Jessica M; Jackson, Austin R; Nagarkatti, Prakash S; Nagarkatti, Mitzi

2016-09-01

∆(9)-Tetrahydrocannabinol (THC) is one of the major bioactive cannabinoids derived from the Cannabis sativa plant and is known for its anti-inflammatory properties. Delayed-type hypersensitivity (DTH) is driven by proinflammatory T helper cells including the classic inflammatory Th1 lineage as well as the more recently discovered Th17 lineage. In the current study, we investigated whether THC can alter the induction of Th1/Th17 cells involved in mBSA-induced DTH response. THC treatment (20 mg/kg) of C57BL/6 mice with DTH caused decreased swelling and infiltration of immune cells at the site of antigen rechallenge. Additionally, THC treatment decreased lymphocyte activation as well as Th1/Th17 lineage commitment, including reduced lineage-specific transcription factors and cytokines. Interestingly, while DTH caused an overexpression of miR-21, which increases Th17 differentiation via SMAD7 inhibition, and downregulation of miR-29b, an IFN-γ inhibitor, THC treatment reversed this microRNA (miR) dysregulation. Furthermore, when we transfected primary cells from DTH mice with miR-21 inhibitor or miR-29b mimic, as seen with THC treatment, the expression of target gene message was directly impacted increasing SMAD7 and decreasing IFN-γ expression, respectively. In summary, the current study suggests that THC treatment during DTH response can simultaneously inhibit Th1/Th17 activation via regulation of microRNA (miRNA) expression. • THC treatment inhibits simultaneous Th1/Th17 driven inflammation. • THC treatment corrects DTH-mediated microRNA dysregulation. • THC treatment regulates proinflammatory cytokines and transcription factors.

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

Science.gov (United States)

Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

2017-05-01

Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Residual cannabis levels in blood, urine and oral fluid following heavy cannabis use.

Science.gov (United States)

Odell, Morris S; Frei, Matthew Y; Gerostamoulos, Dimitri; Chu, Mark; Lubman, Dan I

2015-04-01

An understanding of tetrahydrocannabinol (THC) kinetics and residual levels after cannabis use is essential in interpreting toxicology tests in body fluids from live subjects, particularly when used in forensic settings for drug abuse, traffic and interpersonal violence cases. However the current literature is largely based on laboratory studies using controlled cannabis dosages in experienced users, with limited research investigating the kinetics of residual THC concentrations in regular high dose cannabis users. Twenty-one dependent cannabis users were recruited at admission to two residential detoxification units in Melbourne, Australia. After being provided with information about, and consenting to, the study, subjects volunteered to provide once-daily blood, urine and oral fluid (saliva) samples for seven consecutive days following admission, involving cessation and abstinence from all cannabis use. Blood and oral fluid specimens were analysed for THC and urine specimens for the metabolite THC-COOH. In some subjects THC was detectable in blood for at least 7 days and oral fluid specimens were positive for THC up to 78 h after admission to the unit. Urinary THC-COOH concentrations exceeded 1000 ng/mL for some subjects 129 h after last use. The presented blood THC levels are higher and persist longer in some individuals than previously described, our understanding and interpretation of THC levels in long term heavy cannabis users may need to be reconsidered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The gearing function of running shoe longitudinal bending stiffness.

Science.gov (United States)

Willwacher, Steffen; König, Manuel; Braunstein, Björn; Goldmann, Jan-Peter; Brüggemann, Gert-Peter

2014-07-01

The purpose of the present study was to investigate whether altered longitudinal bending stiffness (LBS) levels of the midsole of a running shoe lead to a systematic change in lower extremity joint lever arms of the ground reaction force (GRF). Joint moments and GRF lever arms in the sagittal plane were determined from 19 male subjects running at 3.5 m/s using inverse dynamics procedures. LBS was manipulated using carbon fiber insoles of 1.9 mm and 3.2 mm thickness. Increasing LBS led to a significant shift of joint lever arms to a more anterior position. Effects were more pronounced at distal joints. Ankle joint moments were not significantly increased in the presence of higher GRF lever arms when averaged over all subjects. Still, two individual strategies (1: increase ankle joint moments while keeping push-off times almost constant, 2: decrease ankle joint moments and increase push-off times) could be identified in response to increased ankle joint lever arms that might reflect individual differences between subjects with respect to strength capacities or anthropometric characteristics. The results of the present study indicate that LBS systematically influences GRF lever arms of lower extremity joints during the push-off phase in running. Further, individual responses to altered LBS levels could be identified that could aid in finding optimum LBS values for a given individual. Copyright © 2014 Elsevier B.V. All rights reserved.

End-User Attitudes towards Location-Based Services and Future Mobile Wireless Devices: The Students’ Perspective

Directory of Open Access Journals (Sweden)

Bogdan Cramariuc

2011-07-01

Full Text Available Nowadays, location-enabled mobile phones are becoming more and more widespread. Various players in the mobile business forecast that, in the future, a significant part of total wireless revenue will come from Location-Based Services (LBS. An LBS system extracts information about the user’s geographical location and provides services based on the positioning information. A successful LBS service should create value for the end-user, by satisfying some of the users’ needs or wants, and at the same time preserving the key factors of the mobile wireless device, such as low costs, low battery consumption, and small size. From many users’ perspectives, location services and mobile location capabilities are still rather poorly known and poorly understood. The aim of this research is to investigate users’ views on the LBS, their requirements in terms of mobile device characteristics, their concerns in terms of privacy and usability, and their opinion on LBS applications that might increase the social wellbeing in the future wireless world. Our research is based on two surveys performed among 105 students (average student age: 24 years from two European technical universities. The survey questions were intended to solicit the youngsters’ views on present and future technological trends and on their perceived needs and wishes regarding Location-Based Services, with the aim of obtaining a better understanding of designer constraints when building a location receiver and generating new ideas related to potential future killer LBS applications.

Changing Information Retrieval Behaviours

DEFF Research Database (Denmark)

Constantiou, Ioanna D.; Lehrer, Christiane; Hess, Thomas

2014-01-01

on the continuance of LBS use and indicate changes in individuals' information retrieval behaviours in everyday life. In particular, the distinct value dimension of LBS in specific contexts of use changes individuals' behaviours towards accessing location-related information....

The Bristol "Badminton" Airplane

Science.gov (United States)

1926-01-01

The Bristol Badminton, Type 99 airplane has a radial aircooled engine (a Bristol Jupiter 9 cylinder 450 HP.) and three fuel tanks. It is a single seat biplane weighing 1,840 lbs. empty and 2,460 lbs. loaded.

Fluorine-18 labeled tetrahydrocannabinol: Synthesis and PET studies in a boron

International Nuclear Information System (INIS)

Marciniak, G.; Charalambous, A.; Makriyannis, A.; Shiue, C.Y.; Dewey, S.L.; Schlyer, D.J.; Wolf, A.P.

1990-01-01

Cannabinoids, the active components of marijuana are known to be psychotic. The most active components of this class of compound are delta-9-tetrahydrocannabinol (Δ 9 -THC) and its delta-8 isomer. While Δ 8 -THC and Δ 9 -THC have similar psychotic activity, Δ 8 -THC is more stable than its Δ 9 analog. Recently, several cannabinoids are found to have high binding affinity to the brain. However, little is known about the mechanisms of their actions. In order to study its pharmacokinetic in animals, the authors have synthesized fluorine-18 labeled 5'-fluoro-Δ 8 -THC and studied its distribution in mice and in a baboon brain

Attempts to retreat from a dead-ended long capillary by backward swimming in Paramecium

Directory of Open Access Journals (Sweden)

Itsuki eKunita

2014-06-01

Full Text Available We have observed how the ciliate Paramecium attempts to retreat from the dead-end of a long capillary that is too narrow for turning. After many trial-and-error episodes of short-term backward swimming (SBS, which is the conventional avoidance behavior exhibited in free swimming when an obstacle is faced, long-term backward swimming (LBS that lasted five to ten times longer was developed. LBS may have a beneficial effect for complete withdrawal from the capillary space, although in our experiment it was impossible for the organism to do so due to the capillary length. In order to identify a physically possible mechanism for LBS, we propose model equations for the membrane potential of Hodgkin-Huxley type, which describe the control of ciliary movement. The physiological implications and physical mechanism of the development of LBS are discussed.

Phase evolution and dielectric properties of MgTi2O5 ceramic sintered with lithium borosilicate glass

International Nuclear Information System (INIS)

Shin, Hyunho; Shin, Hee-Kyun; Jung, Hyun Suk; Cho, Seo-Yong; Hong, Kug Sun

2005-01-01

Phase evolution, densification, and dielectric properties of MgTi 2 O 5 dielectric ceramic, sintered with lithium borosilicate (LBS) glass, were studied. Reaction between LBS glass and MgTi 2 O 5 was significant in forming secondary phases such as TiO 2 and (Mg,Ti) 2 (BO 3 )O. The glass addition was not necessarily deleterious to the dielectric properties due to the formation of TiO 2 : permittivity increased and temperature coefficient of resonance frequency could be tuned to zero with the addition of LBS glass, although the inevitable glass-induced decrease of quality factor was not retarded by the formation of TiO 2 . The sintered specimen with 10 wt% LBS fired at 950 deg. C for 2 h showed permittivity of 19.3, quality factor of 6800 GHz, and τ f of -16 ppm/ deg. C

Artificial intelligence applications of fast optical memory access

Science.gov (United States)

Henshaw, P. D.; Todtenkopf, A. B.

The operating principles and performance of rapid laser beam-steering (LBS) techniques are reviewed and illustrated with diagrams; their applicability to fast optical-memory (disk) access is evaluated; and the implications of fast access for the design of expert systems are discussed. LBS methods examined include analog deflection (source motion, wavefront tilt, and phased arrays), digital deflection (polarization modulation, reflectivity modulation, interferometric switching, and waveguide deflection), and photorefractive LBS. The disk-access problem is considered, and typical LBS requirements are listed as 38,000 beam positions, rotational latency 25 ms, one-sector rotation time 1.5 ms, and intersector space 87 microsec. The value of rapid access for increasing the power of expert systems (by permitting better organization of blocks of information) is illustrated by summarizing the learning process of the MVP-FORTH system (Park, 1983).

Analysis of Cannabinoids and Their Metabolites in Human Urine

OpenAIRE

Wei, Binnian; Wang, Lanqing; Blount, Benjamin C.

2015-01-01

Biologically monitoring marijuana exposure from active and passive use requires both a wide linear range and sensitive detection. We have developed and validated a multifunctional method using ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) for analysis of urinary Δ9-tetrahydrocannabinol (THC), cannabidiol and cannabinol, and two major metabolites of THC, 11-nor-9-carboxy-THC and 11-hydroxy-THC, in active users and particularly in people exposed...

Δ8-Tetrahydrocannabinol induces cytotoxicity in macrophage J774-1 cells: Involvement of cannabinoid receptor 2 and p38 MAPK

International Nuclear Information System (INIS)

Yamaori, Satoshi; Ishii, Hirosuke; Chiba, Kenzo; Yamamoto, Ikuo; Watanabe, Kazuhito

2013-01-01

Tetrahydrocannabinol (THC), a psychoactive component of marijuana, is known to exert cytotoxicity in immune cells. In the present study, we examined the cytotoxicity of Δ 8 -THC in mouse macrophage J774-1 cells and a possible involvement of cannabinoid receptors and stress-responsive mitogen-activated protein kinases (MAPKs) in the cytotoxic process. J774-1 cells were treated with Δ 8 -THC (0–20 μM) for up to 6 h. As measured by the MTT and LDH assays, Δ 8 -THC induced cell death of J774-1 cells in a concentration- and/or exposure time-dependent manner. Δ 8 -THC-induced cell damage was associated with vacuole formation, cell swelling, chromatin condensation, and nuclear fragmentation. The cytotoxic effect of Δ 8 -THC was significantly prevented by a caspase-1 inhibitor Ac-YVAD-cmk but not a caspase-3 inhibitor z-DEVD-fmk. The pretreatment with SR144528, a CB 2 receptor-selective antagonist, effectively suppressed Δ 8 -THC-induced cytotoxicity in J774-1 cells, which exclusively expressed CB 2 receptors as indicated by real-time polymerase chain reaction analysis. In contrast, AM251, a CB 1 receptor-selective antagonist, did not affect the cytotoxicity. Pertussis toxin and α-tocopherol significantly attenuated Δ 8 -THC-induced cytotoxicity suggesting that G i/o protein coupling signal transduction and oxidative stress are responsible for the cytotoxicity. Δ 8 -THC stimulated the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) in J774-1 cells, which were effectively antagonized by the pretreatment with SR144528. In addition, SB203580, a p38 MARK inhibitor, significantly attenuated the cytotoxic effect of Δ 8 -THC, whereas SP600125, a JNK inhibitor, significantly enhanced the cytotoxicity. These results suggest that the cytotoxicity of Δ 8 -THC to J774-1 cells is exerted mediated through the CB 2 receptor followed by the activation of p38 MAPK

Modulation of Δ9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase

International Nuclear Information System (INIS)

Takeda, Shuso; Yamamoto, Ikuo; Watanabe, Kazuhito

2009-01-01

Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Δ 9 -Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17β-estradiol (E 2 ), the interaction of Δ 9 -THC and E 2 in MCF-7 cell growth is not fully clarified so far. In the present study, by using E 2 -sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Δ 9 -THC-mediated MCF-7 cell proliferation. It was shown that Δ 9 -THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Δ 9 -THC was not stimulated by PGE 2 , and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE 2 , suggesting that there is a disconnection between COX-2 (PGE 2 ) and aromatase in Δ 9 -THC-mediated MCF-7 cell proliferation. On the other hand, Δ 9 -THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Δ 9 -THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E 2 , it is suggested that (1) the growth stimulatory effects of Δ 9 -THC are mediated by the product(s) of COX-2 except for PGE 2 , (2) the action of Δ 9 -THC is modulated by E 2 , and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Δ 9 -THC.

Origin and climatic impact of a thermo-haline changes in next centuries in the IPSL-CM4 coupled model

International Nuclear Information System (INIS)

Swingedouw, D.

2006-11-01

The thermo-haline circulation (THC) strongly influences the climate of the North Atlantic. The warming caused by the release of anthropic CO 2 risks to affect this oceanic circulation and then the climate. In this thesis we point to evaluate this risk and to understand the climatic impact of the THC in the future thanks to the tri-dimensional ocean-atmosphere-sea-ice-land IPSL-CM4 coupled model. In a first part we have done a survey of the principal theories and knowledge concerning the THC. We have then validated the pertinence of IPSL-CM4 to lead our study. The role of the salt has appeared primordial for the dynamics of the THC. Then, we have evaluated the sensitivity of the THC to the global fresh water forcing of the ocean. Different sensitivities of the convection sites of the North Atlantic, related to salinity transport process, have been revealed in IPSL-CM4. We have then analysed some scenario simulations for next centuries. It has appeared a significant diminution of the THC in those simulations, which is strongly magnified if the melting of Greenland is taken in account. The analysis of several scenarios taking into account or not this glacier melting has permitted to isolate in an original manner the role played by THC feedbacks. Last, the effect of the THC on the climate has been quantified in IPSL-CM4. It appears to be more slight that the global warming, even locally on Europe. The explanation of the mechanisms at the origin of the influence of the THC on climate has also been clarified. The impact of the THC on the oceanic carbon uptake in the ocean has been lastly evaluated, and appears to be very small on 140 years. This study thus gives a clear vision of the role of the THC on the climate and its possible future. (author)

Tensor hypercontraction. II. Least-squares renormalization

Science.gov (United States)

Parrish, Robert M.; Hohenstein, Edward G.; Martínez, Todd J.; Sherrill, C. David

2012-12-01

The least-squares tensor hypercontraction (LS-THC) representation for the electron repulsion integral (ERI) tensor is presented. Recently, we developed the generic tensor hypercontraction (THC) ansatz, which represents the fourth-order ERI tensor as a product of five second-order tensors [E. G. Hohenstein, R. M. Parrish, and T. J. Martínez, J. Chem. Phys. 137, 044103 (2012)], 10.1063/1.4732310. Our initial algorithm for the generation of the THC factors involved a two-sided invocation of overlap-metric density fitting, followed by a PARAFAC decomposition, and is denoted PARAFAC tensor hypercontraction (PF-THC). LS-THC supersedes PF-THC by producing the THC factors through a least-squares renormalization of a spatial quadrature over the otherwise singular 1/r12 operator. Remarkably, an analytical and simple formula for the LS-THC factors exists. Using this formula, the factors may be generated with O(N^5) effort if exact integrals are decomposed, or O(N^4) effort if the decomposition is applied to density-fitted integrals, using any choice of density fitting metric. The accuracy of LS-THC is explored for a range of systems using both conventional and density-fitted integrals in the context of MP2. The grid fitting error is found to be negligible even for extremely sparse spatial quadrature grids. For the case of density-fitted integrals, the additional error incurred by the grid fitting step is generally markedly smaller than the underlying Coulomb-metric density fitting error. The present results, coupled with our previously published factorizations of MP2 and MP3, provide an efficient, robust O(N^4) approach to both methods. Moreover, LS-THC is generally applicable to many other methods in quantum chemistry.

Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ9-tetrahydrocannabinol in human CD4+ T cells

International Nuclear Information System (INIS)

Ngaotepprutaram, Thitirat; Kaplan, Barbara L.F.; Kaminski, Norbert E.

2013-01-01

We have previously reported that Δ 9 -tetrahydrocannabinol (Δ 9 -THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4 + T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of Δ 9 -THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with Δ 9 -THC attenuated CD40L expression in human CD4 + T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that Δ 9 -THC suppressed the DNA-binding activity of both NFAT and NFκB to their respective response elements within the CD40L promoter. An assessment of the effect of Δ 9 -THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β. Collectively, these findings identify perturbation of the calcium-NFAT and NFκB signaling cascade as a key mechanistic event by which Δ 9 -THC suppresses human T cell function. - Highlights: • Δ 9 -THC attenuated CD40L expression in activated human CD4+ T cells. • Δ 9 -THC suppressed DNA-binding activity of NFAT and NFκB. • Δ 9 -THC impaired elevation of intracellular Ca2+. • Δ 9 -THC did not affect phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β

Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ{sup 9}-tetrahydrocannabinol in human CD4{sup +} T cells

Energy Technology Data Exchange (ETDEWEB)

Ngaotepprutaram, Thitirat [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States); Kaplan, Barbara L.F. [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States); Neuroscience Program, Michigan State University (United States); Kaminski, Norbert E., E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University (United States); Center for Integrative Toxicology, Michigan State University (United States)

2013-11-15

We have previously reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4{sup +} T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of Δ{sup 9}-THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with Δ{sup 9}-THC attenuated CD40L expression in human CD4{sup +} T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that Δ{sup 9}-THC suppressed the DNA-binding activity of both NFAT and NFκB to their respective response elements within the CD40L promoter. An assessment of the effect of Δ{sup 9}-THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β. Collectively, these findings identify perturbation of the calcium-NFAT and NFκB signaling cascade as a key mechanistic event by which Δ{sup 9}-THC suppresses human T cell function. - Highlights: • Δ{sup 9}-THC attenuated CD40L expression in activated human CD4+ T cells. • Δ{sup 9}-THC suppressed DNA-binding activity of NFAT and NFκB. • Δ{sup 9}-THC impaired elevation of intracellular Ca2+. • Δ{sup 9}-THC did not affect phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β.

Effects of chronic Δ9-tetrahydrocannabinol treatment on Rho/Rho-kinase signalization pathway in mouse brain

Directory of Open Access Journals (Sweden)

Halil Mahir Kaplan

2017-11-01

Full Text Available Δ9-Tetrahydrocannabinol (Δ9-THC shows its effects by activating cannabinoid receptors which are on some tissues and neurons. Cannabinoid systems have role on cell proliferation and development of neurons. Furthermore, it is interesting that cannabinoid system and rho/rho-kinase signalization pathway, which have important role on cell development and proliferation, may have role on neuron proliferation and development together. Thus, a study is planned to investigate rhoA and rho-kinase enzyme expressions and their activities in the brain of chronic Δ9-THC treated mice. One group of mice are treated with Δ9-THC once to see effects of acute treatment. Another group of mice are treated with Δ9-THC three times per day for one month. After this period, rhoA and rho-kinase enzyme expressions and their activities in mice brains are analyzed by ELISA method. Chronic administration of Δ9-THC decreased the expression of rhoA while acute treatment has no meaningful effect on it. Administration of Δ9-THC did not affect expression of rho-kinase on both chronic and acute treatment. Administration of Δ9-THC increased rho-kinase activity on both chronic and acute treatment, however, chronic treatment decreased its activity with respect to acute treatment. This study showed that chronic Δ9-THC treatment down-regulated rhoA expression and did not change the expression level of rho-kinase which is downstream effector of rhoA. However, it elevated the rho-kinase activity. Δ9-THC induced down-regulation of rhoA may cause elevation of cypin expression and may have benefit on cypin related diseases. Furthermore, use of rho-kinase inhibitors and Δ9-THC together can be useful on rho-kinase related diseases.

Direct antigonadal activity of cannabinoids: suppression of rat granulosa cell functions.

Science.gov (United States)

Adashi, E Y; Jones, P B; Hsueh, A J

1983-02-01

The direct effects of delta 9-tetrahydrocannabinol (THC) and related cannabinoids on ovarian granulosa cells were studied in vitro. Granulosa cells from immature, hypophysectomized, estrogen-treated rats were cultured for 2 days in an androstenedione-supplemented medium in the presence or absence of follicle-stimulating hormone (FSH) (10 ng/ml) with or without cannabinoids. FSH treatment increased progesterone and estrogen biosynthesis, whereas concomitant treatment with THC led to a dose-dependent inhibition of the FSH-stimulated accumulation of progesterone and estrogen with ED50 values of 3.5 +/- 0.3 X 10(-7) and 1.8 +/- 0.2 X 10(-6) M, respectively. Treatment with related but nonpsychoactive cannabinoids (cannabidiol, cannabinol, cannabigerol, or cannabichromene) was equally effective. The THC-induced inhibition of progesterone production was reversible and was associated with an inhibition of pregnenolone biosynthesis and a decrease of 3 beta-hydroxysteroid dehydrogenase activity. In addition, treatment with THC brought about a dose-dependent inhibition of the FSH-induced increase in luteinizing hormone (LH) receptors. The inhibitory effects of THC were not associated with changes in cell number, protein content, or cell viability. Thus, THC exerts direct inhibitory effects on FSH-dependent functions related to steroidogenesis and the acquisition of LH receptors, all of which are essential to follicular maturation. Because plasma concentrations of THC similar to those used in this study have been reported in human beings, repeated exposure of female users to THC may lead to ovarian dysfunction, due in part, to the direct antigonadal activity to THC.

Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis

NARCIS (Netherlands)

Aizpurua-Olaizola, Oier; Zarandona, Iratxe; Ortiz, Laura; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz

A high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) method for simultaneous quantification of Δ9-tetrahydrocannabinol (THC), its two metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), and four

Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

Directory of Open Access Journals (Sweden)

Valérie Wolff

2015-01-01

Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

Death by self-mutilation after oral cannabis consumption.

Science.gov (United States)

Delteil, Clemence; Sastre, Caroline; Piercecchi, Marie-Dominique; Faget-Agius, Catherine; Deveaux, Marc; Kintz, Pascal; Devooght, Marc-Antoine; Leonetti, George; Bartoli, Christophe; Pélissier-Alicot, Anne-Laure

2018-01-01

Major self-mutilation (amputation, castration, self-inflicted eye injuries) is frequently associated with psychiatric disorders and/or substance abuse. A 35-year-old man presented with behavioral disturbances of sudden onset after oral cannabis consumption and major self-mutilation (attempted amputation of the right arm, self-enucleation of both eyes and impalement) which resulted in death. During the enquiry, four fragments of a substance resembling cannabis resin were seized at the victim's home. Autopsy confirmed that death was related to hemorrhage following the mutilations. Toxicological findings showed cannabinoids in femoral blood (tetrahydrocannabinol (THC) 13.5 ng/mL, 11-hydroxy-tetrahydrocannabinol (11-OH-THC) 4.1 ng/mL, 11-nor-9-carboxy-THC (THC-COOH) 14.7 ng/mL, cannabidiol (CBD) 1.3 ng/mL, cannabinol (CBN) 0.7 ng/mL). Cannabinoid concentrations in hair (1.5 cm brown hair strand/1 segment) were consistent with concentrations measured in chronic users (THC 137 pg/mg, 11-OH-THC 1 pg/mg, CBD 9 pg/mg, CBN 94 pg/mg). Analysis of the fragments seized confirmed that this was cannabis resin with high levels of THC (31-35%). We discuss the implications of oral consumption of cannabis with a very high THC content. Copyright © 2017 Elsevier B.V. All rights reserved.

Considering Affective Responses towards Environments for Enhancing Location Based Services

Science.gov (United States)

Huang, H.; Gartner, G.; Klettner, S.; Schmidt, M.

2014-04-01

A number of studies in the field of environmental psychology show that humans perceive and evaluate their surroundings affectively. Some places are experienced as unsafe, while some others as attractive and interesting. Experiences from daily life show that many of our daily behaviours and decision-making are often influenced by this kind of affective responses towards environments. Location based services (LBS) are often designed to assist and support people's behaviours and decision-making in space. In order to provide services with high usefulness (usability and utility), LBS should consider these kinds of affective responses towards environments. This paper reports on the results of a research project, which studies how people's affective responses towards environments can be modelled and acquired, as well as how LBS can benefit by considering these affective responses. As one of the most popular LBS applications, mobile pedestrian navigation systems are used as an example for illustration.

The structure and mechanical properties of heat treated Al-Zn-Cu-Mg type alloy

Directory of Open Access Journals (Sweden)

M. Kaczorowski

2008-03-01

Full Text Available The results of precipitation hardcning 7075 typc cold workcd alloy arc prcscntcd. Thc aim of thc study was to clnhoratc an Al-Zn-Cu-Mgtypc light alloy for spccial application. Thc most imponant was to proposc thc hcat trentmcnt paramclers which would idlow rcach rhcexkremely high tensile properties with god ductility. Thesc propcrtics was as follow: tcnsilc strcnglh > 640MPa. R , > fi(X1MPi1 and Athc sotittion hcat trcatrncnt at thc tcrnpcrarurc 520°C wit11 conling in cold waicr. Thcrempcraturc 125°C was chosen for aging. The dillcrcnt aging timc was applied for thc spccirncn ai'tcr solu~ianh cnt trcatmcnt I'nllowctl wi11iquenching in cold water. The mechanical prqXI'lics of hcat trcatcd spccimcns wcrc ~cstcdi n tcnsion and usi~igh ardncss mcasurcmcnl.Besides the conventional MetalIography. scanning (SEMI and transmission electron microscopy (TEM were applied Tor stnlcturcohscwations. In case of the last onc we used either microscopy observations whcrc tilting cxpcrimcnt was uscd ant1 sclcc~ctnl rcn clcc~ro~ldiffraction (SAD.

[Neuropsychopharmacology of delta-9-tetrahydrocannabinol].

Science.gov (United States)

Costentin, J

2008-08-01

Today, the main route of introduction of tetrahydrocannabinol (THC), the main active substance of cannabis, into the human body is via the lungs, from smokes produced by combustion of a haschich-tobacco mixture. The use of a water pipe (nargileh-like) intensifies its fast supply to the body. THC reaches the brain easily where it stimulates CB1 receptors; their ubiquity underlies a wide variety of effects. THC disappears from extracellular spaces by dissolving in lipid rich membranes, and not by excretion from the body. This is followed by a slow release, leading to long lasting effects originating from brain areas containing a large proportion of spare receptors ("reserve receptors"). Far from mimicking the effects of endocannabinoids, THC caricatures and disturbs them. It induces both psychical and physical dependencies, but the perception of withdrawal is weak on account of its very slow elimination. THC disturbs cognition. Acutely, it develops anxiolytic- and antidepressant-like effects, which causes a lot of users to abuse THC, thus leading to a tolerance (desensitization of CB1 receptors) making anxiety and depression to reappear more intensely than originally. THC has close relationships with schizophrenia. It incites to tobacco, alcohol and heroine abuses.

Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L.

Science.gov (United States)

Formukong, E A; Evans, A T; Evans, F J

1988-02-01

Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings.

The elimination half-life of benzodiazepines and fall risk: two prospective observational studies.

Science.gov (United States)

de Vries, Oscar J; Peeters, Geeske; Elders, Petra; Sonnenberg, Caroline; Muller, Majon; Deeg, Dorly J H; Lips, Paul

2013-11-01

the STOPP criteria advise against the use of long-acting benzodiazepines (LBs). to study whether LBs are associated with a higher fall risk than short-acting benzodiazepines (SBs) (elimination half-life ≤ 10 h). we used base-line data and prospective fall follow-up from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study including 1,509 community-dwelling older persons (Study 1) and from a separate fall prevention study with 564 older persons after a fall (Study 2). Time to the first fall after inclusion and number of falls in the first year after inclusion were the primary endpoints. both in Study 1 and Study 2 the use of SBs was associated with time to the first fall, hazard ratio (HR) 1.62 (95% CI: 1.03-2.56) and HR 1.64 (95% CI: 1.19-2.26),respectively. LBs were not significantly associated with time to first fall, HR 1.40 (0.85-2.31) and HR 1.08 (0.72-1.62). In both studies, the use of SBs was also associated with number of falls, odds ratio (OR) 1.28 (95% CI: 1.01-1.61) and OR 1.37 (95% CI: 1.10-1.70). LBs were not significantly associated with number of falls, OR 1.23 (0.96-1.57) and 1.10 (0.82-1.48). the use of SBs is not associated with a lower fall risk compared with LBs. The use of both SBs and LBs by old persons should be strongly discouraged.

Agreement among Classroom Observers of Children's Stylistic Learning Behaviors.

Science.gov (United States)

Buchanan, Helen Hamlet; McDermott, Paul A.; Schaefer, Barbara A.

1998-01-01

Investigates the interobserver agreement of the Learning Behavior Scale (LBS) by educators (n=16) observing students in special-education classes (n=72). No significant observer effect was found. Moreover, the LBS produced comparable levels of differential learning styles for assessments of individual children. (Author/MKA)

Fatigue evaluation of the increased weight limit on transit railway bridges.

Science.gov (United States)

2014-09-01

The recent increase of freight railcar weight limits from 263,000 lbs. to 286,000 lbs. raises concerns for the safety of bridges : on transit passenger rail systems, since they were not designed for this weight increase. Thus, there is a need to asse...

Flight test of a spin parachute for use with a Super Arcas sounding rocket

Science.gov (United States)

Silbert, M. N.

1975-01-01

The development and flight testing of a specially configured 16.6 ft Disc Band Gap (DBG) Spin Parachute is discussed. The parachute is integrated with a modified Super Arcas launch vehicle. Total payload weight was 17.6 lbs including the Spin Parachute and a scientific payload, and lift-off weight was 100.3 lbs. The Super Arcas vehicle was despun from 18.4 cps. After payload separation at 244,170 ft the Spin Parachute and its payload attained a maximum spin rate of 2.4 cps. Total suspended weight of the Spin Parachute and its payload was 14.64 lbs.

Ontology-Based Retrieval of Spatially Related Objects for Location Based Services

Science.gov (United States)

Haav, Hele-Mai; Kaljuvee, Aivi; Luts, Martin; Vajakas, Toivo

Advanced Location Based Service (LBS) applications have to integrate information stored in GIS, information about users' preferences (profile) as well as contextual information and information about application itself. Ontology engineering provides methods to semantically integrate several data sources. We propose an ontology-driven LBS development framework: the paper describes the architecture of ontologies and their usage for retrieval of spatially related objects relevant to the user. Our main contribution is to enable personalised ontology driven LBS by providing a novel approach for defining personalised semantic spatial relationships by means of ontologies. The approach is illustrated by an industrial case study.

40 CFR Table 3 to Subpart Lllll of... - Requirements for Performance Tests a,b

Science.gov (United States)

2010-07-01

... port's location and the number of traverse points i. EPA test method 1 or 1A in appendix A to part 60..., THC destruction efficiency, THC outlet concentration, or combustion efficiency standards, the sampling... combustion efficiency or THC standards a. Measure the concentration of carbon dioxideb. Measure the...

Improving the prediction of in-sewer transformation of illicit drug biomarkers by identifying a new modelling framework

DEFF Research Database (Denmark)

Ramin, Pedram; Brock, Andreas Libonati; Polesel, Fabio

-3-β-D-glucuronide; codeine and its metabolite norcodeine; methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP); mephedrone; and tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-Δ9-THC (THCOH), and 11-nor-9-carboxy-Δ9-THC (THCCOOH). All the transformation....... Furthermore, abiotic transformation was found to be the main transformation mechanism for THC (aerobic conditions); mephedrone, methadone, cocaine, ecgonine methyl ester, cocaethylene, THCOH and THCCOOH (anaerobic conditions). By use of the proposed model the uncertainty of predicting illicit drug...

Perfusion of the isolated rat brain with [14C]-Δ1-tetrahydrocannabinol

International Nuclear Information System (INIS)

Martin, B.; Agurell, S.; Krieglstein, J.; Rieger, H.

1977-01-01

There is controversy over whether Δ 1 -tetrahydrocannabinol (Δ 1 -THC) or its metabolites is responsible for the behavioural and cardiovascular effects of cannabis. It has been shown that, even in the absence of metabolism, Δ 1 -THC was capable of altering the EEG of isolated perfused rat brain, and must therefore contribute to the psychoactivity of cannabis. TLC studies showed no evidence for brain metabolism of [ 14 C]-Δ 1 -THC, and in particular the 7-hydroxylated metabolite (7-OH-Δ 1 -THC) could not be detected. A disproportionate amount of CNS activity in the rat cannot therefore be attributed to 7-OH-Δ 1 -THC on the basis that it is formed at or near its locus of action. (U.K.)

40 CFR 63.5915 - What records must I keep?

Science.gov (United States)

2010-07-01

... Standards for Hazardous Air Pollutants: Reinforced Plastic Composites Production Notifications, Reports, and... section, when complying with the percent reduction and/or lbs/ton requirements specified in paragraphs (a... determine percent reduction and/or lbs/ton as applicable; (2) You must keep a brief description of the...

Novel time-dependent vascular actions of Δ9-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

International Nuclear Information System (INIS)

O'Sullivan, Saoirse E.; Tarling, Elizabeth J.; Bennett, Andrew J.; Kendall, David A.; Randall, Michael D.

2005-01-01

Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, Δ 9 -tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPARγ). In vitro, THC (10 μM) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPARγ agonist rosiglitazone and was inhibited by the PPARγ antagonist GW9662 (1 μM), but not the cannabinoid CB 1 receptor antagonist AM251 (1 μM). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPARγ, transiently expressed in combination with retinoid X receptor α and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 μM). In vitro incubation with THC (1 or 10 μM, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPARγ ligands. The present results provide strong evidence that THC is a PPARγ ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors

Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

Energy Technology Data Exchange (ETDEWEB)

O' Sullivan, Saoirse E [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Tarling, Elizabeth J [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Bennett, Andrew J [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Kendall, David A [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom); Randall, Michael D [School of Biomedical Sciences, E Floor, Queen' s Medical Centre, University of Nottingham, Nottingham NG7 2UH (United Kingdom)

2005-11-25

Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.

Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells

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Xiao Han

2016-02-01

Full Text Available Background: Tetrahydrocurcumin (THC, an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. Methods: The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF-7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. Results: THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 μM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 μM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Δψm was observed after THC treatment. Conclusion: THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound.

INTERFERENCE OF THE RUNNING WAVES AT LIGHT BRIDGES OF A SUNSPOT

Energy Technology Data Exchange (ETDEWEB)

Su, J. T.; Priya, T. G.; Yu, S. J.; Zhang, M. [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Ji, K. F. [Kunming University of Science and Technology, Kunming 650093 (China); Banerjee, D. [Indian Institute of Astrophysics, Koramangala Bangalore 560034 (India); Cao, W. D. [Big Bear Solar Observatory, 40386 North Shore Lane, Big Bear City, CA 92314 (United States); Zhao, J. S.; Ji, H. S., E-mail: jt@bao.ac.cn [Purple Mountain Observatory, CAS, Nanjing 210008 (China)

2016-01-01

The observations of chromospheric oscillations of two umbral light bridges (LBs) within a sunspot from NOAA Active Region 12127 are presented. It was found that the running umbral waves with periods of 2.2–2.6 minutes underwent very fast damping before approaching umbral boundaries, while those with higher periods (>2.6 minutes) could propagate outside umbrae. On two sides of each LB adjacent to umbrae, the cross-wavelet spectra displayed that the oscillations on them had a common significant power region with dominant frequencies of 2–6 minutes and phase differences of ∼90°. A counterstream of two running umbral waves in the 2–6 minute frequency range propagated toward the LBs, where they encountered each other and gave rise to constructive or even destructive interference on the LBs. In addition, the velocity and density perturbations on the LBs were found in opposite phases suggesting that the perturbations were caused by the downward propagating waves.

Potency trends of Δ9-tetrahydrocannabinol, cannabidiol and cannabinol in cannabis in the Netherlands: 2005-15.

Science.gov (United States)

Niesink, Raymond J M; Rigter, Sander; Koeter, Maarten W; Brunt, Tibor M

2015-12-01

Between 2000 and 2005 the average percentage of Δ(9) -tetrahydrocannabinol (THC) in marijuana as sold in Dutch coffeeshops has increased substantially; the potency of domestic products (Nederwiet and Nederhasj) has particularly increased. In contrast with imported marijuana, Nederwiet hardly contained any cannabidiol (CBD), a cannabinoid that is thought to offset some of the adverse effects of THC. In 2005, the THC content in Nederwiet was significantly lower than in 2004. This study investigates the further decrease or increase of cannabinoids in these cannabis products. From 2005 to 2015 five different cannabis products were bought anonymously in 50 coffeeshops that were selected randomly each year from all coffeeshops in the Netherlands. A total of 2126 cannabis samples were bought, consisting of 664 Nederwiet samples (most popular), 537 Nederwiet samples (supposed strongest varieties), 183 imported herbal cannabis samples, 140 samples of cannabis resin made of Nederwiet and 602 samples of imported cannabis resin. All samples were analysed chemically for their THC, CBD and cannabinol (CBN) content. Between 2005 and 2015, the mean potencies of the most popular and the strongest Nederwiet and of imported cannabis resin were 16.0±4.0%, 17.0±3,9% and 16.5±6.3%, respectively. Imported herbal cannabis (6.5±3.5%) and cannabis resin made from Nederwiet (30.2±16.4%) contained, respectively, less (β=-10.0, P<0.001) and more (β=13.7, P<0.001) THC than imported cannabis resin. Linear regression models were used to study the trends in THC of the different cannabis products over time. A marginal, but significant (P<0.001), overall decline of THC per year of 0.22% was found in all cannabis products. However, no significant difference was found between the five products in the THC linear trajectories across time. Of all the cannabis products, only imported cannabis resin contained a relatively high CBD/THC ratio (median 0.42). The average tetrahydrocannabinol (THC

LBS Management Review - Vol 4, No 1 (1999)

African Journals Online (AJOL)

dx.doi.org/10.4314/lbsmr.v4i1.24463 · Leveraging your Database for Effective Direct Marketing. Vincent Onyemah. http://dx.doi.org/10.4314/lbsmr.v4i1.24464 · A Measurement Approach for Process Improvement. Evans Woherem.

LBS Management Review - Vol 5, No 2 (2000)

African Journals Online (AJOL)

Upgrading your Quality Management System to ISO 9000 Standards · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Eugene Okolie, 73-81. http://dx.doi.org/10.4314/lbsmr.v5i2.24448 ...

A Hybrid Location Privacy Solution for Mobile LBS

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Ruchika Gupta

2017-01-01

Full Text Available The prevalent usage of location based services, where getting any service is solely based on the user’s current location, has raised an extreme concern over location privacy of the user. Generalized approaches dealing with location privacy, referred to as cloaking and obfuscation, are mainly based on a trusted third party, in which all the data remain available at a central server and thus complete knowledge of the query exists at the central node. This is the major limitation of such approaches; on the other hand, in trusted third-party-free framework clients collaborate with each other and freely communicate with the service provider without any third-party involvement. Measuring and evaluating trust among peers is a crucial aspect in trusted third-party-free framework. This paper exploits the merits and mitigating the shortcomings of both of these approaches. We propose a hybrid solution, HYB, to achieve location privacy for the mobile users who use location services frequently. The proposed HYB scheme is based on the collaborative preprocessing of location data and utilizes the benefits of homomorphic encryption technique. Location privacy is achieved at two levels, namely, at the proximity level and at distant level. The proposed HYB solution preserves the user’s location privacy effectively under specific, pull-based, sporadic query scenario.

Travel risk behaviors as a determinants of receiving pre-travel health consultation and prevention.

Science.gov (United States)

Shady, Ibrahim; Gaafer, Mohammed; Bassiony, Lamiaa

2015-01-01

An estimated 30-60 % of travelers experience an illness while traveling. The incidence of travel-related illness can be reduced by preventive measures such as those provided by the Traveler Health Clinic (THC) in Kuwait. The present study is an analytical comparative study between groups of travelers visiting the THC during the study period (May 2009 - December 2010) and an age- and gender-matched control group of non-visitors (800 people). Both groups completed a modified pre-departure questionnaire. Bivariate analysis revealed that Kuwaitis (68.2 %), those traveling for work (25.3 %) or leisure (59.5 %), those living in camps (20.4 %) or hotels (64.0 %), and those with knowledge of the THC from the media (28.1 %) or other sources (57.3 %), were more likely to be associated with a high frequency of visits to the THC ( p  travelers heading to Africa (47 %) and South America (10 %) visited the THC more than did others ( P  travel, duration of stay, and choice of travel destination are independent predictors of receiving pre-travel consultation from the THC. Nationality, purpose of travel, length of stay, and travel destination are predictors for receiving a pre-travel consultation from the THC.

Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol

International Nuclear Information System (INIS)

Johansson, E.; Gillespie, H.K.; Halldin, M.M.

1990-01-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [ 14 C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14 C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14 C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively

The study of precipitation hardening of weight heavy alloys matrix

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M. Kaczorowski

2008-03-01

Full Text Available Thc study of rnodcl wcight hcavy atloy (WHA W-Ni-Co-Fc. with somc cxccss or tungsrcn with respcct to its maximum nickcI hascd sol idstate solubility arc prcscntcd. The alloy was melted at the tcmpemturc 1570 "C in hydrogcn atrnosphcrc. Aftet rcmoving thc bottom par1 ofthc cwting where cxcess grains of tungstcn scdimcnt, thc ingot was solulion heat trcatmcnt for 2h at tbc tcmpcra~urc 900°C followed hywater qucnching. Finally. the specimens werc agcd at thc tcrnpcraturc 250. 3IX1 and 350 "C for time up to 48. 36 and 24 rcspcctivcly. Aficrheat trcazment the specimens wcre studicd using hardncss rncasutemcnts and structure investigations. Thc last onc includcd X-raydiffracromctry (XRD. optical metallography. scanning clcct ton microscopy (SEM and ~ransmissionrl cctron micmscopy (TEMb I t wasconcluded that two phase microstructure was not s~lhstantiallyc hangcd during aging. cspially the aging lcad not ta 111tr;l-finc prccipitnzcformation. which would causcd remnrkablc prccipizar ion strcng~hcningo f mn~rixT. hc rcsulzs analysis prompt us to concludc thna thc mainreason of minimal strcngthcning only was thc spccific output strtlcturc aftcr solution heat tscatrnen!. rcsul~cd Fmm to taw tclnpcraturc ofsolution heat treatment,

Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

Energy Technology Data Exchange (ETDEWEB)

Johansson, E.; Gillespie, H.K.; Halldin, M.M. (BMC, Uppsala (Sweden))

1990-05-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol.

Science.gov (United States)

Boggs, Douglas L; Nguyen, Jacques D; Morgenson, Daralyn; Taffe, Michael A; Ranganathan, Mohini

2018-01-01

The plant Cannabis sativa, commonly called cannabis or marijuana, has been used for its psychotropic and mind-altering side effects for millennia. There has been growing attention in recent years on its potential therapeutic efficacy as municipalities and legislative bodies in the United States, Canada, and other countries grapple with enacting policy to facilitate the use of cannabis or its constituents for medical purposes. There are >550 chemical compounds and >100 phytocannabinoids isolated from cannabis, including Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is thought to produce the main psychoactive effects of cannabis, while CBD does not appear to have similar effects. Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC. This includes effects of CBD on THC-induced anxiety, psychosis, and cognitive deficits. In this article, we review the available evidence on the pharmacology and behavioral interactions of THC and CBD from preclinical and human studies, particularly with reference to anxiety and psychosis-like symptoms. Both THC and CBD, as well as other cannabinoid molecules, are currently being evaluated for medicinal purposes, separately and in combination. Future cannabis-related policy decisions should include consideration of scientific findings, including the individual and interactive effects of CBD and THC.

[Testing the pharmacological activity of some synthetic cannabinoids in mice (author's transl)].

Science.gov (United States)

Ganz, A J; Waser, P G

1980-01-01

A series of synthetic cannabinoids were tested in mice for analgesic, anticonvulsant, sedative and reserpine antagonistic properties as well as for influence on body temperature and on motor coordination and compared with the natural delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol (delta 8-THC) and cannabidiol (CBD). All cannabinoids were injected s.c. or i.p. in mice as solutions in olive oil. The synthetic cannabinoids, with the exception of the lipophilic ones, were less active than the natural delta 9-THC. 1',1'-dimethyl-delta 8-tetrahydrocannabinol (DM-delta 8-THC) has an analgesic ED 50 of 16 mg/kg s.c. (writhing test) and is three times more active than delta 9-THC, but also eight times less active than morphine. The lipophilic derivatives of delta 8-THC prolonged pentobarbitone narcosis and diminished locomotor activity in mice. Anticonvulsant activities could never be detected; all cannabinoids slightly diminished body temperature and antagonized weakly the hypothermia induced by reserpine. The trained capacity of remaining on the rotating rod was severely shortened for a long time after application of all cannabinoids but mainly by the lipophilic ones. The influence of derivation on the activity of delta 9-THC is discussed.

Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

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George Panagis

2017-04-01

Full Text Available Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ9-tetrahydrocannabinol (Δ9-THC induces transgenerational effects on the reward-facilitating effects of Δ9-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ9-THC (0.1 or 1 mg/kg, i.p. or vehicle during postnatal days 28–50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ9-THC’s (0, 0.1, 0.5, and 1 mg/kg, i.p. and d-amphetamine’s (0, 0.1, 0.5, and 1 mg/kg, i.p. reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ9-THC was abolished in the F1 offspring of females that were exposed to Δ9-THC (0.1 or 1 mg/kg, whereas the reward-attenuating effect of the 1 mg dose of Δ9-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ9-THC (1 mg/kg and 0.1 or 1 mg, respectively. The present results reveal that female Δ9-THC exposure during adolescence can diminish the reward-facilitating effects of Δ9-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ9-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

Finding Lawrence: Recruiting Talent for Unconventional Warfare

Science.gov (United States)

2011-06-01

equipment (55 lbs rucksack and 10 lbs weapon), culminating in a 40-mile trek to be completed in less than 20 hours.101 Those deemed not suitable, but who...involvement, targeted recruitment for interpersonal intelligence and cross-cultural capability could help achieve for SF what NASA achieved during its

40 CFR 412.40 - Applicability.

Science.gov (United States)

2010-07-01

... CONCENTRATED ANIMAL FEEDING OPERATIONS (CAFO) POINT SOURCE CATEGORY Swine, Poultry, and Veal Calves § 412.40 Applicability. This subpart applies to operations defined as concentrated animal feeding operations (CAFOs... lbs. or more; 10,000 swine each weighing less than 55 lbs.; 30,000 laying hens or broilers if the...

Generation of Functional Lentoid Bodies From Human Induced Pluripotent Stem Cells Derived From Urinary Cells.

Science.gov (United States)

Fu, Qiuli; Qin, Zhenwei; Jin, Xiuming; Zhang, Lifang; Chen, Zhijian; He, Jiliang; Ji, Junfeng; Yao, Ke

2017-01-01

The pathological mechanisms underlying cataract formation remain largely unknown on account of the lack of appropriate in vitro cellular models. The aim of this study is to develop a stable in vitro system for human lens regeneration using pluripotent stem cells. Isolated human urinary cells were infected with four Yamanaka factors to generate urinary human induced pluripotent stem cells (UiPSCs), which were induced to differentiate into lens progenitor cells and lentoid bodies (LBs). The expression of lens-specific markers was examined by real-time PCR, immunostaining, and Western blotting. The structure and magnifying ability of LBs were investigated using transmission electron microscopy and observing the magnification of the letter "X," respectively. We developed a "fried egg" differentiation method to generate functional LBs from UiPSCs. The UiPSC-derived LBs exhibited crystalline lens-like morphology and a transparent structure and expressed lens-specific markers αA-, αB-, β-, and γ-crystallin and MIP. During LB differentiation, the placodal markers SIX1, EYA1, DLX3, PAX6, and the specific early lens markers SOX1, PROX1, FOXE3, αA-, and αB-crystallin were observed at certain time points. Microscopic examination revealed the presence of lens epithelial cells adjacent to the lens capsule as well as both immature and mature fiber-like cells. Optical analysis further demonstrated the magnifying ability (1.7×) of the LBs generated from UiPSCs. Our study provides the first evidence toward generating functional LBs from UiPSCs, thereby establishing an in vitro system that can be used to study human lens development and cataractogenesis and perhaps even be useful for drug screening.

Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver.

Science.gov (United States)

Harvey, D J; Martin, B R; Paton, W D

1977-08-01

In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.

Perfusion of the isolated rat brain with (/sup 14/C)-. delta. /sup 1/-tetrahydrocannabinol

Energy Technology Data Exchange (ETDEWEB)

Martin, B; Agurell, S [Dept. of Pharmacognosy, Faculty of Pharmacy, BMC, Uppsala (Sweden); Krieglstein, J; Rieger, H

1977-12-01

There is controversy over whether ..delta../sup 1/-tetrahydrocannabinol (..delta../sup 1/-THC) or its metabolites is responsible for the behavioural and cardiovascular effects of cannabis. It has been shown that, even in the absence of metabolism, ..delta../sup 1/-THC was capable of altering the EEG of isolated perfused rat brain, and must therefore contribute to the psychoactivity of cannabis. TLC studies showed no evidence for brain metabolism of (/sup 14/C)-..delta../sup 1/-THC, and in particular the 7-hydroxylated metabolite (7-OH-..delta../sup 1/-THC) could not be detected. A disproportionate amount of CNS activity in the rat cannot therefore be attributed to 7-OH-..delta../sup 1/-THC on the basis that it is formed at or near its locus of action.

Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

Directory of Open Access Journals (Sweden)

Gideon W Blumstein

Full Text Available Delta-9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5 C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg treatment on mice infected with a non-lethal dose of 7.5×10(4 C. albicans on day 2, followed by a higher challenge with 5×10(5 C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.

Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

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Wendy Swift

Full Text Available Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9-tetrahydrocannabinol (THC and low levels of other phytocannabinoids, particularly cannabidiol (CBD. Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales "Cannabis Cautioning" scheme. A further 26 "Known Provenance" samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG, and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC, cannabinol (CBN and tetrahydrocannabivarin (THC-V. The "Cannabis Cautioning" samples showed high mean THC content (THC+THC-A = 14.88% and low mean CBD content (CBD+CBD-A = 0.14%. A modest level of CBG was detected (CBG+CBG-A = 1.18% and very low levels of CBC, CBN and THC-V (<0.1%. "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

Science.gov (United States)

Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

2018-02-17

Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

Science.gov (United States)

Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

2015-12-01

Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

Medicinal applications of delta-9-tetrahydrocannabinol and marijuana.

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Voth, E A; Schwartz, R H

1997-05-15

The use of crude marijuana for herbal medicinal applications is now being widely discussed in both the medical and lay literature. Ballot initiatives in California and Arizona have recently made crude marijuana accessible to patients under certain circumstances. As medicinal applications of pure forms of delta-9-tetrahydrocannabinol (THC) and crude marijuana are being considered, the most promising uses of any form of THC are to counteract the nausea associated with cancer chemotherapy and to stimulate appetite. We evaluated the relevant research published between 1975 and 1996 on the medical applications, physical complications, and legal precedents for the use of pure THC or crude marijuana. Our review focused on the medical use of THC derivatives for nausea associated with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord spasticity. Despite the toxicity of THC delivered in any form, evidence supports the selective use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite. The evidence does not support the reclassification of crude marijuana as a prescribable medicine.

Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme.

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Dolores Hernán Pérez de la Ossa

Full Text Available Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9-Tetrahydrocannabinol (THC and Cannabidiol (CBD - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease

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Kalia, Lorraine V.; Lang, Anthony E.; Hazrati, Lili-Naz; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Hurtig, Howard I.; Alcalay, Roy N.; Marder, Karen S.; Clark, Lorraine N.; Gaig, Carles; Tolosa, Eduardo; Ruiz-Martínez, Javier; Marti-Masso, Jose F.; Ferrer, Isidre; de Munain, Adolfo López; Goldman, Samuel M.; Schüle, Birgitt; Langston, J. William; Aasly, Jan O.; Giordana, Maria T.; Bonifati, Vincenzo; Puschmann, Andreas; Canesi, Margherita; Pezzoli, Gianni; De Paula, Andre Maues; Hasegawa, Kazuko; Duyckaerts, Charles; Brice, Alexis; Stoessl, A. Jon; Marras, Connie

2015-01-01

IMPORTANCE Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment. PMID:25401511

Effect of breeding method and season on pregnancy rate and embryonic and fetal losses in lactating Nili-Ravi buffaloes.

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Qayyum, Arslan; Arshad, Usman; Yousuf, Muhammad Rizwan; Ahmad, Nasim

2018-03-01

The aim of this study was to determine the effect of breeding method and season on pregnancy rate and cumulative embryonic and fetal losses in Nili-Ravi buffalo. Estrus detection was performed twice a day by teaser buffalo bull for 1 hour each. A 2 × 2 factorial design was used to address the breeding method and season. Buffaloes (n = 130) exhibiting estrus were randomly assigned to be bred either in peak breeding season (PBS; n = 80) or low breeding season (LBS; n = 50). Within each season, buffaloes were divided to receive either natural service (NS; n = 65) or artificial insemination (AI; n = 65). NS buffaloes, in estrus, were allowed to remain with the bull until mating. AI was achieved, using frozen thawed semen of bull of known fertility. PBS comprised of September to December and LBS were from May to July. Serial ultrasonography was performed on days 30, 45, 60, and 90 after breeding (day 0) to monitor pregnancy rate and embryonic and fetal losses. The pregnancy rate on day 30 after breeding was higher in NS as compared to AI group (63 vs. 43%; P  0.05) in LBS. The cumulative embryonic and fetal losses between days 31 and 90 were significantly lower in PBS than LBS (33 vs. 60%; P losses were higher in LBS in Nili-Ravi buffalo.

Lifetime-broadening-suppressed X-ray absorption spectrum of β-YbAlB4 deduced from Yb 3d → 2p resonant X-ray emission spectroscopy

International Nuclear Information System (INIS)

Kawamura, Naomi; Mizumaki, Masaichiro; Kanai, Noriko; Hayashi, Hisashi; Matsuda, Yasuhiro H.; Kuga, Kentaro; Nakatsuji, Satoru; Watanabe, Shinji

2017-01-01

In this work, the Yb 3d → 2p (Yb Lα 1,2 ) resonant X-ray emission spectrum of β-YbAlB 4 was acquired using excitation energies around the Yb L 3 -edge, at 2 K. Subsequently, the lifetime-broadening-suppressed (LBS) X-ray absorption structure (XAS) spectrum was obtained using the SIM-RIXS program. This spectrum was found to exhibit clearly resolved pre-edge and shoulder structures. Resonant Lα 1 emission spectra were well reproduced from LBS-XAS profiles over wide ranges of excitation and emission energies. In contrast, noticeable discrepancies appeared between the experimental and simulated Lα 2 emission spectra, suggesting an effect resulting from M 4 M 5 O 1 Coster-Kronig transitions. LBS-XAS, in conjunction with partial fluorescence yield (PFY) XAS and transmission XAS, determined a value for the Yb valence (v) in β-YbAlB 4 of 2.76 ± 0.08 at 2 K. Despite this relatively large uncertainty in v, each method provided a consistent variation in valence (δv) as the temperature was raised from 2 to 280 K: 0.060 ± 0.004 (LBS-XAS), 0.061 ± 0.005 (PFY-XAS) and 0.058 ± 0.007 (transmission XAS). The smaller δv associated with LBS-XAS demonstrates the greater precision of this method. (author)

Processing Advantages of Lexical Bundles: Evidence from Self-Paced Reading and Sentence Recall Tasks

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Tremblay, Antoine; Derwing, Bruce; Libben, Gary; Westbury, Chris

2011-01-01

This article examines the extent to which lexical bundles (LBs; i.e., frequently recurring strings of words that often span traditional syntactic boundaries) are stored and processed holistically. Three self-paced reading experiments compared sentences containing LBs (e.g., "in the middle of the") and matched control sentence fragments (e.g., "in…

Foursquare: A Health Education Specialist Checks-In--A Commentary

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Haithcox-Dennis, Melissa

2011-01-01

More and more, health education specialists are integrating technology into their work. Whereas most are familiar with social media sites like Facebook, Twitter and LinkedIn, one relatively new form of social media, location based services (LBS), may be less familiar. Developed in 2000, LBS are software applications that are accessible from a…

The Learning Behaviors Scale: National Standardization in Trinidad and Tobago

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Chao, Jessica L.; McDermott, Paul A.; Watkins, Marley W.; Drogalis, Anna Rhoad; Worrell, Frank C.; Hall, Tracey E.

2018-01-01

This study reports on the national standardization and validation of the Learning Behaviors Scale (LBS) for use in Trinidad and Tobago. The LBS is a teacher rating scale centering on observable behaviors relevant to identifying childhood approaches to classroom learning. Teachers observed a stratified sample of 900 students across the islands'…

The influence of the

Directory of Open Access Journals (Sweden)

Konopka Z.

2008-03-01

Full Text Available Results of cxarnination of the AISi12Cu2 alloy mcchanical properties achicvcd by pressure carring with usc of horizontal coldchamhcr rnachinc employing rhc "full slccvc" construc~ion at various proccss paramctcrs have been prcscntcd. Bath Ihc piston velocityduring injcction and thc intensification pressurc havc hccn changed according to thc factor cxperimcnt dcsign Rcgrcssion rclarionshipsbetween mchanical propenics of alloy and the variablc paramctcrs of carting havc kcn Found both for thc convcniional mlhod and forthc "full steeve" construction. The analysis of results paints to an incrcase in strength and pIastic properties of the invcstigatitcd alloy castby ~h"cfu lt sleeve" mczhod as compared with these propcriics for the alloy cast by convcntianal mcihod. A strong influcncc of plungervclocity and prcssure on thc cxarnincd propcnies of castings produccd by thc two methods hns hccn slntctt.

Faecal and protozoan parasite contamination of water spinach (Ipomoea aquatica) cultivated in urban wastewater in Phnom Penh, Cambodia

DEFF Research Database (Denmark)

Anh, Vuong Tuan; Tram, Nguyen Thuy; Klank, Lise Tønner

2007-01-01

Objective To identify the level of contamination with thermotolerant coliforms (ThC), intestinal helminth eggs and protozoan parasites in water spinach (Ipomoea aquatica) cultivated in a wastewater-fed lake in Phnom Penh, Cambodia. Methods The investigation was carried out from July 2004 to May...... into a stream. Water spinach samples were harvested at each of the three locations with and without wastewater contact according to the normal practices of farmers, and analysed for ThC, protozoan parasites (Giardia, Cryptosporidium and Cyclospora), and helminth eggs (Ascaris lumbricoides, Trichuris trichura...... and hookworm) using standard methods. Wastewater samples were also collected at each of the three locations and analysed for ThC and helminth eggs. Results High concentrations of ThC (approximately 10(5)-10(7)/g) were found in water spinach samples. ThC mean counts did not differ significantly, neither between...

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

International Nuclear Information System (INIS)

Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Mu, Qingli; Li, Huani

2013-01-01

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue

Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol.

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Busquets-Garcia, Arnau; Gomis-González, Maria; Salgado-Mendialdúa, Victòria; Galera-López, Lorena; Puighermanal, Emma; Martín-García, Elena; Maldonado, Rafael; Ozaita, Andrés

2018-04-01

Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit. Immunoblot analysis revealed a transient increase in PKC signaling activity in the hippocampus after THC treatment. Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. This significant immunoreactive band that paralleled cognitive performance did not match in size with the major PKC isoforms expressed in the hippocampus except for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. These data demonstrate that THC alters short-term object-recognition memory through hippocampal PKC/neurogranin signaling.

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

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Cluny, Nina L.; Keenan, Catherine M.; Reimer, Raylene A.; Le Foll, Bernard; Sharkey, Keith A.

2015-01-01

Objective Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Methods Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. Results THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Conclusions Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity. PMID:26633823

Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

Science.gov (United States)

Lazzari, P; Fadda, P; Marchese, G; Casu, G L; Pani, L

2010-06-30

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs. This sparingly soluble terpeno-phenolic compound is not easy to handle and to be formulated in pharmaceutical preparations. The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment. Due to the thermodynamic stability and advantages of microemulsion based systems, the study was focused on the identification of aqueous microemulsion based systems containing Delta(9)-THC. Oil in water Delta(9)-THC microemulsions were individuated through phase diagrams construction, using the non-ionic surfactant Solutol HS15, being this surfactant acceptable for parenteral administration in human. A selected microemulsion samples containing 0.2 wt% of Delta(9)-THC, stable up to 52 degrees C, was successfully assayed on animal models of pain. Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation. The effect has been highlighted in shorter time if compared to a preparation of the same active principle based on previously reported conventional preparation. 2010 Elsevier B.V. All rights reserved.

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

Energy Technology Data Exchange (ETDEWEB)

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

2013-10-01

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

Bioethanol Production by Calcium Alginate-Immobilised St1 Yeast System: Effects of Size of Beads, Ratio and Concentration

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Masniroszaime Md Zain

2011-12-01

Full Text Available Immobilized yeast-cell technology posses several advantages in bioethanol production due to its potential to increase the ethanol yield by eliminating unit process used. Thus, process expenses in cell recovery and reutilization can be minimised. The aim of this study is to investigate the influence of three parameters (substrate concentrations, size of alginate beads and ratio of volume of beads to volume of medium on local isolated yeast (ST1 which immobilized using calcium alginate fermentation system. The most affected ethanol production by calcium alginate-immobilised ST1 yeast system were ratio of volume of the beads to the volume of substrate and concentration of LBS. Highest theoretical yield, 78% was obtained in ST1-alginate beads with the size of beads 0.5cm, ratio volume of beads to the volume of LBS media 0.4 and 150g/l concentration of LBS.ABSTRAK: Teknologi sel yis pegun memiliki beberapa kelebihan dalam penghasilan bioetanol kerana ia berpotensi meningkatkan pengeluaran etanol dengan menyingkirkan unit proses yang digunakan. Maka, proses pembiayaan dalam perolehan sel dan penggunaan semula boleh dikurangkan. Tujuan kajian ini adalah untuk mengkaji pengaruh tiga parameter (kepekatan substrat, saiz manik alginat dan nisbah isipadu manik terhadap isipadu bahantara ke atas sel tempatan terasing (local isolated yeast (ST1 yang dipegun menggunakan sistem penapaian kalsium alginat. Penghasilan etanol yang paling berkesan dengan menggunakan sistem yis ST1 kalsium alginat-pegun adalah dengan kadar nisbah isipadu manik terhadap isipadu substrat dan kepekatan LBS. Kadar hasil teori tertinggi iaitu 78% didapati menerusi manik alginat-ST1 dengan saiz manik 0.5cm, nisbah isipadu 0.4 terhadap perantara LBS dan kepekatan LBS sebanyak 150g/l. Normal 0 false false false EN-US X-NONE X-NONE

Discordance Between Body Mass Index (BMI) and a Novel Body Composition Change Index (BCCI) as Outcome Measures in Weight Change Interventions.

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Nugent, Stephen D; Kaats, Gilbert R; Preuss, Harry G

2018-01-01

A general assumption is that the body mass index (BMI) reflects changes in fat mass (FM). However, it fails to distinguish the type of weight that is lost or gained-fat mass (FM) or fat-free mass (FFM). The BMI treats both changes the same although they have opposite health consequences. The objective of this study was to propose a more precise measure, a body composition change index (BCCI), which distinguishes between changes in FM and FFM, and this study compares it with using the BMI as an outcome measure. Data were obtained from 3,870 subjects who had completed dual-energy x-ray absorptiometry (DEXA) total body scans at baseline and end-of-study when participating in a variety of weight-loss interventions. Since height remained constant in this adult cohort, changes in the BMI corresponded with scale weight changes (r = 0.994), allowing BMI changes to be converted to "lbs." to match the statistic used for calculation of the BCCI. The BCCI is calculated by scoring increases in FFM (lbs.) and decreases in FM (lbs.) as positive outcomes and scoring decreases in FFM and increases in FM as negative outcomes. The BCCI is the net sum of these calculations. Differences between scale weight changes and BCCI values were subsequently compared to obtain "discordance scores." Discordance scores ranged from 0.0 lbs. to >30.0 lbs. with a mean absolute value of between the two measures of 7.79 lbs. (99% confidence interval: 7.49-8.10, p BCCI and the BMI to evaluate the efficacy of weight loss interventions. If assessing changes in body composition is a treatment goal, use of the BMI could result in significantly erroneous conclusions.

21 CFR 524.1610 - Orbifloxacin, mometasone furoate monohydrate, and posaconazole suspension.

Science.gov (United States)

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL.... 000061 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. For dogs weighing less than 30 lbs. instill 4 drops once daily into the ear canal. For dogs weighing 30 lbs. or more, instill...

46 CFR 193.50-5 - Classification.

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2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Classification. 193.50-5 Section 193.50-5 Shipping COAST... Details § 193.50-5 Classification. (a) Hand portable fire extinguishers and semiportable fire...) Classification Type Size Soda-acid and water, gals. Foam, gals. Carbon dioxide, lbs. Dry chemical, lbs. A II 21/2...

A Real-Time Location-Based Services System Using WiFi Fingerprinting Algorithm for Safety Risk Assessment of Workers in Tunnels

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Peng Lin

2014-01-01

Full Text Available This paper investigates the feasibility of a real-time tunnel location-based services (LBS system to provide workers’ safety protection and various services in concrete dam site. In this study, received signal strength- (RSS- based location using fingerprinting algorithm and artificial neural network (ANN risk assessment is employed for position analysis. This tunnel LBS system achieves an online, real-time, intelligent tracking identification feature, and the on-site running system has many functions such as worker emergency call, track history, and location query. Based on ANN with a strong nonlinear mapping, and large-scale parallel processing capabilities, proposed LBS system is effective to evaluate the risk management on worker safety. The field implementation shows that the proposed location algorithm is reliable and accurate (3 to 5 meters enough for providing real-time positioning service. The proposed LBS system is demonstrated and firstly applied to the second largest hydropower project in the world, to track workers on tunnel site and assure their safety. The results show that the system is simple and easily deployed.

MICROSTRUCTURE AND MECHANICAL STRENGTH OF SURFACE ODS TREATED ZIRCALOY-4 SHEET USING LASER BEAM SCANNING

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HYUN-GIL KIM

2014-08-01

Full Text Available The surface modification of engineering materials by laser beam scanning (LBS allows the improvement of properties in terms of reduced wear, increased corrosion resistance, and better strength. In this study, the laser beam scan method was applied to produce an oxide dispersion strengthened (ODS structure on a zirconium metal surface. A recrystallized Zircaloy-4 alloy sheet with a thickness of 2 mm, and Y2O3 particles of 10 μm were selected for ODS treatment using LBS. Through the LBS method, the Y2O3 particles were dispersed in the Zircaloy-4 sheet surface at a thickness of 0.4 mm, which was about 20% when compared to the initial sheet thickness. The mean size of the dispersive particles was 20 nm, and the yield strength of the ODS treated plate at 500°C was increased more than 65 % when compared to the initial state. This strength increase was caused by dispersive Y2O3 particles in the matrix and the martensite transformation of Zircaloy-4 matrix by the LBS.

Refurbishing the plasmodesmal chamber: a role for lipid bodies?

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Laju K Paul

2014-02-01

Full Text Available Lipid bodies (LBs are universal constituents of both animal and plant cells. They are produced by specialised membrane domains at the tubular endoplasmic reticulum (ER, and consist of a core of neutral lipids and a surrounding monolayer of phospholipid with embedded amphipathic proteins. Although originally regarded as simple depots for lipids, they have recently emerged as organelles that interact with other cellular constituents, exchanging lipids, proteins and signalling molecules, and shuttling them between various intracellular destinations, including the plasmamembrane (PM. Recent data showed that in plants LBs can deliver a subset of 1,3-β-glucanases to the plasmodesmal (PD channel. We hypothesise that this may represent a more general mechanism, which complements the delivery of GPI-anchored proteins to the PD exterior via the secretory pathway. We propose that LBs may contribute to the maintenance of the PD chamber and the delivery of regulatory molecules as well as proteins destined for transport to adjacent cells. In addition, we speculate that LBs deliver their cargo through interaction with membrane domains in the cytofacial side of the PM.

Passive cannabis smoke exposure and oral fluid testing. II. Two studies of extreme cannabis smoke exposure in a motor vehicle.

Science.gov (United States)

Niedbala, R Sam; Kardos, Keith W; Fritch, Dean F; Kunsman, Kenneth P; Blum, Kristen A; Newland, Gregory A; Waga, Joe; Kurtz, Lisa; Bronsgeest, Matth; Cone, Edward J

2005-10-01

Two studies were conducted to determine if extreme passive exposure to cannabis smoke in a motor vehicle would produce positive results for delta-tetrahydrocannabinol (THC) in oral fluid. Passive exposure to cannabis smoke in an unventilated room has been shown to produce a transient appearance of THC in oral fluid for up to 30 min. However, it is well known that such factors as room size and extent of smoke exposure can affect results. Questions have also been raised concerning the effects of tobacco when mixed with marijuana and THC content. We conducted two passive cannabis studies under severe passive smoke exposure conditions in an unventilated eight-passenger van. Four passive subjects sat alongside four active cannabis smokers who each smoked a single cannabis cigarette containing either 5.4%, 39.5 mg THC (Study 1) or 10.4%, 83.2 mg THC (Study 2). The cigarettes in Study 1 contained tobacco mixed with cannabis; cigarettes in Study 2 contained only cannabis. Oral fluid specimens were collected from passive and active subjects with the Intercept Oral Specimen Collection Device for 1 h after smoking cessation while inside the van (Study 1) and up to 72 h (passive) or 8 h (active) outside the van. Additionally in Study 1, Intercept collectors were exposed to smoke in the van to assess environmental contamination during collection procedures. For Study 2, all oral fluid collections were outside the van following smoking cessation to minimize environmental contamination. Oral samples were analyzed with the Cannabinoids Intercept MICRO-PLATE EIA and quantitatively by gas chromatography-tandem mass spectrometry (GC-MS-MS). THC concentrations were adjusted for dilution (x 3). The screening and confirmation cutoff concentrations for THC in neat oral fluid were 3 ng/mL and 1.5 ng/mL, respectively. The limits of detection (LOD) and quantitation (LOQ) for THC in the GC-MS-MS assay were 0.3 and 0.75 ng/mL, respectively. Urine specimens were collected, screened (EMIT, 50

Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

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Vandrey, Ryan; Herrmann, Evan S; Mitchell, John M; Bigelow, George E; Flegel, Ronald; LoDico, Charles; Cone, Edward J

2017-03-01

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of

Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile

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Li, Kong M.; Arnold, Jonathon C.; McGregor, Iain S.

2013-01-01

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed. PMID:23894589

Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ(9) tetrahydrocannabinol.

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Wright, M Jerry; Vandewater, Sophia A; Taffe, Michael A

2013-12-01

Recent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ(9) tetrahydrocannabinol (THC) content. Self-selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship. In this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self-Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg(-1) , i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg(-1) CBD. CBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self-Ordered Spatial Search task of working memory. CBD did not significantly reverse THC-induced impairment of a progressive ratio or a rotating turntable task. This study provides direct evidence that CBD can oppose the cognitive-impairing effects of THC and that it does so in a task-selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing therapeutic products may therefore help to ameliorate unwanted cognitive side-effects. This article is commented on by Mechoulam and Parker, pp 1363-1364 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12400. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

Concentrations of delta9-tetrahydrocannabinol and 11-nor-9-carboxytetrahydrocannabinol in blood and urine after passive exposure to Cannabis smoke in a coffee shop.

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Röhrich, J; Schimmel, I; Zörntlein, S; Becker, J; Drobnik, S; Kaufmann, T; Kuntz, V; Urban, R

2010-05-01

Cannabinoid concentrations in blood and urine after passive exposure to cannabis smoke under real-life conditions were investigated in this study. Eight healthy volunteers were exposed to cannabis smoke for 3 h in a well-attended coffee shop in Maastricht, Netherlands. An initial blood and urine sample was taken from each volunteer before exposure. Blood samples were taken 1.5, 3.5, 6, and 14 h after start of initial exposure, and urine samples were taken after 3.5, 6, 14, 36, 60, and 84 h. The samples were subjected to immunoassay screening for cannabinoids and analyzed using gas chromatography-mass spectrometry (GC-MS) for Delta(9)-tetrahydrocannabinol (THC), 11-nor-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH). It could be demonstrated that all volunteers absorbed THC. However, the detected concentrations were rather small. None of the urine samples produced immunoassay results above the cutoff concentration of 25 ng/mL. THC-COOH concentrations up to 5.0 and 7.8 ng/mL before and after hydrolysis, respectively, were found in the quantitative GC-MS analysis of urine. THC could be detected in trace amounts close to the detection limit of the used method in the first two blood samples after initial exposure (1.5 and 3.5 h). In the 6 h blood samples, THC was not detectable anymore. THC-COOH could be detected after 1.5 h and was still found in 3 out of 8 blood samples after 14 h in concentrations between 0.5 and 1.0 ng/mL.

Cannabis Intoxication Case Series: The Dangers of Edibles Containing Tetrahydrocannabinol.

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Vo, Kathy T; Horng, Howard; Li, Kai; Ho, Raymond Y; Wu, Alan H B; Lynch, Kara L; Smollin, Craig G

2018-03-01

Cannabis and its principal active constituent, Δ9-tetrahydrocannabinol (THC), are increasingly available as edibles resembling commercially available food products. In this case series, we describe a population of predominantly pediatric patients who were inadvertently exposed to a THC-containing product in San Francisco. Twelve children and 9 adults were identified, with 16 patients having detectable serum THC and THC metabolites. All patients presented to hospitals with a variety of constitutional symptoms and all were discharged home within 12 hours. In general, pediatric patients had more severe symptoms and longer hospital length of stay, and, uniquely, a majority presented with leukocytosis and elevated lactic acid levels. We recommend that efforts be made to increase general public awareness in regard to the potential hazards of THC-containing edibles resembling commercially available food products. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Policy-Aware Sender Anonymity in Location-Based Services

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Vyas, Avinash

2011-01-01

Sender anonymity in Location-based services (LBS) refers to hiding the identity of a mobile device user who sends requests to the LBS provider for services in her proximity (e.g. "find the nearest gas station etc."). The goal is to keep the requester's interest private even from attackers who (via hacking or subpoenas) gain access to the LBS…

Technical Evaluation of Dayboard Materials

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1990-03-01

lbs/gal standard still has a number of politica hurdles to clear. Until the issue is resolved, marine coatings with VOC’s exceeding 2.0 lbs/gal can only...formulation of the paint, the preparation of the backing, the skill of the operator applying the paint, and the ambient temperature. Or in other words: more

College Freshman Stress and Weight Change: Differences by Gender

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Economos, Christina D.; Hildebrandt, M. Lise; Hyatt, Raymond R.

2008-01-01

Objectives: To examine how stress and health-related behaviors affect freshman weight change by gender. Methods: Three hundred ninety-six freshmen completed a 40-item health behavior survey and height and weight were collected at baseline and follow-up. Results: Average weight change was 5.04 lbs for males, 5.49 lbs for females. Weight gain was…

Irinotecan and Δ9-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers

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Ana Lucić Vrdoljak

2018-06-01

Full Text Available There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ9-tetrahydrocannabinol (THC with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI, and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w., while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.. Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase—AST, alanine aminotransferase—ALP, alkaline phosphatase—AP, and bilirubin in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations

Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration.

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Newmeyer, Matthew N; Swortwood, Madeleine J; Taylor, Megan E; Abulseoud, Osama A; Woodward, Thomas H; Huestis, Marilyn A

2017-08-01

Establishing science-based driving per se blood Δ 9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Rapid analysis of Δ-9-tetrahydrocannabinol in hair using direct analysis in real time ambient ionization orbitrap mass spectrometry.

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Duvivier, Wilco F; van Beek, Teris A; Pennings, Ed J M; Nielen, Michel W F

2014-04-15

Forensic hair analysis methods are laborious, time-consuming and provide only a rough retrospective estimate of the time of drug intake. Recently, hair imaging methods using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) were reported, but these methods require the application of MALDI matrix and are performed under vacuum. Direct analysis of entire locks of hair without any sample pretreatment and with improved spatial resolution would thus address a need. Hair samples were attached to stainless steel mesh screens and scanned in the X-direction using direct analysis in real time (DART) ambient ionization orbitrap MS. The DART gas temperature and the accuracy of the probed hair zone were optimized using Δ-9-tetrahydrocannabinol (THC) as a model compound. Since external contamination is a major issue in forensic hair analysis, sub-samples were measured before and after dichloromethane decontamination. The relative intensity of the THC signal in spiked blank hair versus that of quinine as the internal standard showed good reproducibility (26% RSD) and linearity of the method (R(2)  = 0.991). With the DART hair scan THC could be detected in hair samples from different chronic cannabis users. The presence of THC was confirmed by quantitative liquid chromatography/tandem mass spectrometry. Zones with different THC content could be clearly distinguished, indicating that the method might be used for retrospective timeline assessments. Detection of THC in decontaminated drug user hair showed that the DART hair scan not only probes THC on the surface of hair, but penetrates deeply enough to measure incorporated THC. A new approach in forensic hair analysis has been developed by probing complete locks of hair using DART-MS. Longitudinal scanning enables detection of incorporated compounds and can be used as pre-screening for THC without sample preparation. The method could also be adjusted for the analysis of other drugs of abuse. Copyright �

Location Prediction Based on Transition Probability Matrices Constructing from Sequential Rules for Spatial-Temporal K-Anonymity Dataset

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Liu, Zhao; Zhu, Yunhong; Wu, Chenxue

2016-01-01

Spatial-temporal k-anonymity has become a mainstream approach among techniques for protection of users’ privacy in location-based services (LBS) applications, and has been applied to several variants such as LBS snapshot queries and continuous queries. Analyzing large-scale spatial-temporal anonymity sets may benefit several LBS applications. In this paper, we propose two location prediction methods based on transition probability matrices constructing from sequential rules for spatial-temporal k-anonymity dataset. First, we define single-step sequential rules mined from sequential spatial-temporal k-anonymity datasets generated from continuous LBS queries for multiple users. We then construct transition probability matrices from mined single-step sequential rules, and normalize the transition probabilities in the transition matrices. Next, we regard a mobility model for an LBS requester as a stationary stochastic process and compute the n-step transition probability matrices by raising the normalized transition probability matrices to the power n. Furthermore, we propose two location prediction methods: rough prediction and accurate prediction. The former achieves the probabilities of arriving at target locations along simple paths those include only current locations, target locations and transition steps. By iteratively combining the probabilities for simple paths with n steps and the probabilities for detailed paths with n-1 steps, the latter method calculates transition probabilities for detailed paths with n steps from current locations to target locations. Finally, we conduct extensive experiments, and correctness and flexibility of our proposed algorithm have been verified. PMID:27508502

In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

International Nuclear Information System (INIS)

Rettori, V.; Aguila, M.C.; McCann, S.M.; Gimeno, M.F.; Franchi, A.M.

1990-01-01

Previous in vivo studies have shown that Δ 9 -tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E 2 (PGE 2 ) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE 2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE 2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release

Effect of gamma-radiation on direct intercellular interaction (rosette formation) between thymus macrophages and thymocytes

International Nuclear Information System (INIS)

Belyakov, I.M.; Yarilin, A.A.

1992-01-01

In experiments with mice, the effect of radiation on resette formation between thymus macrophages (Th-MPh) and thymocytes (Thc) was studied on days 1, 4, 12, 30, and 60 following gamma-irradiation with doses of 0.5, 2, 4, and 8 Gy. gamma-Irradiation with doses of above 2 Gy was shown to cause a dose-dependent inhibition of rosette formation of Th-MPh with Thc in vitro. Two types of rosette-forming Th-MPh were identified: RFMPhII with low rate of binding to Thc and RFMPhII with high rate of binding to Thc. Radiation affects mainly the RFMPhII content. The total population of rosette-forming Th-MPh was restored on day 60 mainly due to cells with low rate of rosette formation. The EC supernatant promoted rosette formation of exposed Th-MPh with Thc. The effect was maximum at early times following irradiation of Th-MPh with a dose of 4 Gy

High-affinity cannabinoid binding site in brain: A possible marijuana receptor

International Nuclear Information System (INIS)

Nye, J.S.

1988-01-01

The mechanism by which delta 9 tetrahydrocannabinol (delta 9 THC), the major psychoactive component of marijuana or hashish, produces its potent psychological and physiological effects is unknown. To find receptor binding sites for THC, we designed a water-soluble analog for use as a radioligand. 5'-Trimethylammonium-delta 8 THC (TMA) is a positively charged analog of delta- 8 THC modified on the 5' carbon, a portion of the molecule not important for its psychoactivity. We have studied the binding of [ 3 H]-5'-trimethylammonium-delta- 8 THC ([ 3 H]TMA) to rat neuronal membranes. [ 3 H]TMA binds saturably and reversibly to brain membranes with high affinity to apparently one class of sites. Highest binding site density occurs in brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacologial properties. Molecular sieve chromatography reveals a bimodal peak of [ 3 H]TMA binding activity of approximately 60,000 daltons apparent molecular weight

In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse.

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Brown, N K; Harvey, D J

1988-04-01

Methyl-delta-8-tetrahydrocannabinol (methyl-delta-8-THC), methyl-delta-9-THC and abn-methyl-delta-8-THC were synthesized by condensation of orcinol and (1S)-cis-verbenol and were administered to male Charles River CD-1 mice. Extracted hepatic metabolites were isolated by chromatography on Sephadex LH-20 and examined by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta-8-THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta-8-THC-11-oic acid. abn-Methyl-delta-8-THC was metabolized in a different manner. The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C(11) to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds. Metabolism of methyl-delta-9-THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C(8) and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta-9-THC-11-oic acid.

Effect of (--∆9-tetrahydrocannabinoid on the hepatic redox state of mice

Directory of Open Access Journals (Sweden)

C.E. Pinto

2010-04-01

Full Text Available (--∆9-Tetrahydrocannabinol (∆9-THC, a psychoactive component of marijuana, has been reported to induce oxidative damage in vivo and in vitro. In this study, we administered ∆9-THC to healthy C57BL/6J mice aged 15 weeks in order to determine its effect on hepatic redox state. Mice were divided into 3 groups: ∆9-THC (N = 10, treated with 10 mg/kg body weight ∆9-THC daily; VCtrl (N = 10, treated with vehicle [1:1:18, cremophor EL® (polyoxyl 35 castor oil/ethanol/saline]; Ctrl (N = 10, treated with saline. Animals were injected ip twice a day with 5 mg/kg body weight for 10 days. Lipid peroxidation, protein carbonylation and DNA oxidation were used as biomarkers of oxidative stress. The endogenous antioxidant defenses analyzed were glutathione (GSH levels as well as enzyme activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, and glutathione peroxidase (GPx in liver homogenates. The levels of mRNA of the cannabinoid receptors CB1 and CB2 were also monitored. Treatment with ∆9-THC did not produce significant changes in oxidative stress markers or in mRNA levels of CB1 and CB2 receptors in the liver of mice, but attenuated the increase in the selenium-dependent GPx activity (Δ9-THC: 8%; VCtrl: 23% increase and the GSH/oxidized GSH ratio (Δ9-THC: 61%; VCtrl: 96% increase, caused by treatment with the vehicle. Δ9-THC administration did not show any harmful effects on lipid peroxidation, protein carboxylation or DNA oxidation in the healthy liver of mice but attenuated unexpected effects produced by the vehicle containing ethanol/cremophor EL®.

Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.

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Manwell, Laurie A; Mallet, Paul E

2015-05-01

Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA). The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined. Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials. Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses. These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.

Determination of cannabinoids in hemp nut products in Taiwan by HPLC-MS/MS coupled with chemometric analysis: quality evaluation and a pilot human study.

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Chang, Chih-Wei; Tung, Chun-Wei; Tsai, Chin-Chuan; Wu, Yu-Tse; Hsu, Mei-Chich

2017-06-01

Hemp nuts are mature cannabis seeds obtained after shelling and that are commonly used in traditional Chinese medicine for treating functional constipation. In this work, we screened hemp nut products, classified them, and verified the legality of consuming them. A total of 18 products were purchased from Taiwan, China, and Canada. Validated high-performance liquid chromatography with tandem mass spectrometry methods were developed for analyzing the cannabinoid (i.e., Δ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol) content of the products and the concentration of urinary 11-nor-9-carboxy-THC. Chemometric techniques, namely hierarchical clustering analysis (HCA) and principal component analysis (PCA), were applied for rapidly classifying 11 concentrated powder products in Taiwan. A pilot human study comprising single and multiple administrations of a product with 1.5 µg/g of THC was conducted to examine the urinary 11-nor-9-carboxy-THC concentration. Through optimization of 3 2 full factorial design, using 60% isopropanol as the extraction solvent exhibited the highest yield of cannabinoids and was applied as the optimal condition in further analysis. The results of HCA and PCA on quality evaluation were in good agreement; however, the tested products possessed distinct CBD-to-THC ratios which ranged widely from 0.1:1 to 46.8:1. Particularly, the products with CBD-to-THC ratios higher than 1:1 were the majority in Taiwan. Our data suggested that all the tested hemp nut products met the Taiwan restriction criterion of 10 µg/g of THC. We propose a usual consumption amount of hemp nut products in Taiwan would unlikely to violate the cut-off point of 15 ng/mL of urinary 11-nor-9-carboxy-THC. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparing treatment effects of oral THC on simulated and on-the-road driving performance: testing the validity of driving simulator drug research.

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Veldstra, J L; Bosker, W M; de Waard, D; Ramaekers, J G; Brookhuis, K A

2015-08-01

The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently. The question is whether it is sensitive to detect drug-induced effects. The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects. As a case in point, we investigated the dose-related effects of oral ∆(9)-tetrahydrocannabinol (THC), i.e. dronabinol, on simulator and on-the-road driving performance in equally demanding driving tasks. Twenty-four experienced driver participants were treated with dronabinol (Marinol®; 10 and 20 mg) and placebo. Dose-related effects of the drug on the ability to keep a vehicle in lane (weaving) and to follow the speed changes of a lead car (car following) were compared within subjects for on-the-road versus in-simulator driving. Additionally, the outcomes of equivalence testing to alcohol-induced effects were investigated. Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road. The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator. There was, however, a differential treatment effect of dronabinol on reactions to speed changes of a lead car (car following) when driving on the road versus when driving in the simulator. The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses. Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving. Car following on the road and in the simulator were, however, not comparable.

Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in Egypt

Institute of Scientific and Technical Information of China (English)

Ahmed M.A.Souleman; Alaa El-Din M. Gaafar; Omar M.Abdel-Salam; Shaimaa A. ElShebiney

2017-01-01

Objective: To determine the delta-9-tetrahydrocannabinol (THC) content of cannabis seizures in Egypt. Methods: Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves (marijuana) or from the resin (hashish) and subjected to analysis using high performance liquid chromatography (HPLC). Results: The heated resin extract had the peak of THC in a relative ratio of 31.34%, while extracting the resin directly without heating contained only 18.34% of THC. On the other hand, marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating. Conclusions:These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market.

Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

Science.gov (United States)

Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

2011-02-01

The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

Ultrasound-guided diffuse optical tomography (DOT) of invasive breast carcinoma: Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status?

Energy Technology Data Exchange (ETDEWEB)

Zhu, Qingli, E-mail: qinglizhu@gmail.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Xiao, Mengsu, E-mail: xiaomengsu_2000@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); You, Shanshan, E-mail: shanshan_0531@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Zhang, Jing, E-mail: zhang.jing1029@163.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Jiang, Yuxin, E-mail: yuxinjiangxh@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Lai, Xingjian, E-mail: lxjpumch@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Dai, Qing, E-mail: qingdai_2000@yahoo.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China)

2012-11-15

Objectives: To prospectively study the ultrasound-guided near-infrared diffuse optical tomography (DOT) findings of the total haemoglobin concentration (THC) detected in invasive breast carcinomas and its contribution to the prediction of axillary lymph node (LN) status. Methods: A total of 195 invasive breast carcinomas were prospectively studied with DOT before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Tumour size and THC level were correlated with LN status by a logistic regression analysis. Results: One hundred twenty-four patients (63.59%) was LN(-) and 71 (36.41%) was LN(+). The average THC was significantly higher in the LN(+) group than in the LN(-) group (252.94 {+-} 69.19 {mu}mol/L versus 203.86 {+-} 83.13 {mu}mol/L, P = 0.01). A multivariate analysis showed an independent relationship between the probability of axillary metastasis, elevated THC level (P = 0.01), and tumour size (P = 0.001). The odds ratio with THC {>=} 140 {mu}mol/L was 13.651 (1.781-104.560), whereas that of tumour size with a 1 cm increment was only 1.777 (1.283-2.246). Conclusions: The THC level and the tumour size are independent and preoperative predictors of axillary nodal status; these variables may improve the diagnosis of patients with lymph node metastasis.

Cannabinoids concentration variability in cannabis olive oil galenic preparations.

Science.gov (United States)

Carcieri, Chiara; Tomasello, Cristina; Simiele, Marco; De Nicolò, Amedeo; Avataneo, Valeria; Canzoneri, Luca; Cusato, Jessica; Di Perri, Giovanni; D'Avolio, Antonio

2018-01-01

Knowledge of the exact concentration of active compounds in galenic preparations is crucial to be able to ensure their quality and to properly administer the prescribed dose. Currently, the need for titration of extracts is still debated. Considering this, together with the absence of a standard preparation method, the aim of this study was to evaluate cannabinoids concentrations variability in galenic olive oil extracts, to evaluate the interlot and interlaboratory variability in the extraction yield and in the preparation composition. Two hundred and one extracts (123 (61.2%) from Bedrocan ® , 54 (26.9%) from Bediol ® , 11 (5.5%) from Bedrolite ® , and 13 (6.5%) from mixed preparations) were analysed by liquid chromatography coupled with tandem mass spectrometry, quantifying cannabinoids (THC, CBD, THCA, CBDA and CBN) concentrations. The RSD% of THC and CBD concentrations resulted higher than 50%. Specifically for Bedrocan ® , Bediol ® , Bedrolite ® (5 g/50 ml), these were THC 82%, THC 53% and CBD 91%, THC 58% and CBD 59%, respectively. The median extraction yields were greater than 75% for all preparations. Our results highlighted a wide variability in THC and CBD concentrations that justify the need for titration and opens further questions about other pharmaceutical preparations without regulatory indication for this procedure. © 2017 Royal Pharmaceutical Society.

Glycolytic pathway (GP), kreb's cycle (KC), and hexose monophosphate shunt (HMS) activity in myocardial subcellular fractions exposed to cannabinoids

Energy Technology Data Exchange (ETDEWEB)

Watson, A.T.; Manno, B.R.; King, J.W.; Fowler, M.R.; Dempsey, C.A.; Manno, J.E.

1986-03-05

Delta-9-tetrahydrocannabinol (..delta../sup 9/-THC), the primary psychoactive component of marihuana, and its active metabolite 11-hydroxy-..delta../sup 9/-tetrahydrocannabinol (11-OH-..delta../sup 9/-THC) have been reported to produce a direct cardiac depressant effect. Studies in isolated perfused rat hearts have indicated a decreased force of contraction (inotropic response) when ..delta../sup 9/-THC or 11-OH-..delta../sup 9/-THC was administered in microgram amounts. The mechanism and site of action have not been explained or correlated with associated metabolic pathways. The purpose of this study was to investigate the effects of cannabinoids on major myocardial energy producing pathways, GP and KC, and a non-energy producing pathway, HMS. Cardiac ventricular tissue from male Sprague-Dawley rats (250-300 g) was excised and homogenized for subcellular fractionation. KC, GP and HMS activity was assayed in the appropriate fractions by measuring /sup 14/CO/sub 2/ generation from /sup 14/C-2-pyruvate, /sup 14/C-6-glucose and /sup 14/C-1-glucose respectively. Duplicate assays (n=8) were performed on tissue exposed to saline (control), empty liposomes (vehicle) and four doses each of ..delta../sup 9/-THC and 11-OH-..delta../sup 9/-THC. Changes in metabolic activity and decreases in cardiac contractile performance may be associated.

Glycolytic pathway (GP), kreb's cycle (KC), and hexose monophosphate shunt (HMS) activity in myocardial subcellular fractions exposed to cannabinoids

International Nuclear Information System (INIS)

Watson, A.T.; Manno, B.R.; King, J.W.; Fowler, M.R.; Dempsey, C.A.; Manno, J.E.

1986-01-01

Delta-9-tetrahydrocannabinol (Δ 9 -THC), the primary psychoactive component of marihuana, and its active metabolite 11-hydroxy-Δ 9 -tetrahydrocannabinol (11-OH-Δ 9 -THC) have been reported to produce a direct cardiac depressant effect. Studies in isolated perfused rat hearts have indicated a decreased force of contraction (inotropic response) when Δ 9 -THC or 11-OH-Δ 9 -THC was administered in microgram amounts. The mechanism and site of action have not been explained or correlated with associated metabolic pathways. The purpose of this study was to investigate the effects of cannabinoids on major myocardial energy producing pathways, GP and KC, and a non-energy producing pathway, HMS. Cardiac ventricular tissue from male Sprague-Dawley rats (250-300 g) was excised and homogenized for subcellular fractionation. KC, GP and HMS activity was assayed in the appropriate fractions by measuring 14 CO 2 generation from 14 C-2-pyruvate, 14 C-6-glucose and 14 C-1-glucose respectively. Duplicate assays (n=8) were performed on tissue exposed to saline (control), empty liposomes (vehicle) and four doses each of Δ 9 -THC and 11-OH-Δ 9 -THC. Changes in metabolic activity and decreases in cardiac contractile performance may be associated

Treatment of Tourette Syndrome with Cannabinoids

Directory of Open Access Journals (Sweden)

Kirsten R. Müller-Vahl

2013-01-01

Full Text Available Cannabinoids have been used for hundred of years for medical purposes. To day, the cannabinoid delta-9-tetrahydrocannabinol (THC and the cannabis extract nabiximols are approved for the treatment of nausea, anorexia and spasticity, respectively. In Tourette syndrome (TS several anecdotal reports provided evidence that marijuana might be effective not only in the suppression of tics, but also in the treatment of associated behavioural problems. At the present time there are only two controlled trials available investigating the effect of THC in the treatment of TS. Using both self and examiner rating scales, in both studies a significant tic reduction could be observed after treatment with THC compared to placebo, without causing significant adverse effects. Available data about the effect of THC on obsessive-compulsive symptoms are inconsistent. According to a recent Cochrane review on the efficacy of cannabinoids in TS, definite conclusions cannot be drawn, because longer trials including a larger number of patients are missing. Notwithstanding this appraisal, by many experts THC is recommended for the treatment of TS in adult patients, when first line treatments failed to improve the tics. In treatment resistant adult patients, therefore, treatment with THC should be taken into consideration.

Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.

Science.gov (United States)

von Bueren, A O; Schlumpf, M; Lichtensteiger, W

2008-01-01

Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

Psychomotor performance, subjective and physiological effects and whole blood Δ⁹-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers following acute smoked cannabis.

Science.gov (United States)

Schwope, David M; Bosker, Wendy M; Ramaekers, Johannes G; Gorelick, David A; Huestis, Marilyn A

2012-07-01

Δ⁹-Tetrahydrocannabinol (THC) is the illicit drug most frequently observed in accident and driving under the influence of drugs investigations. Whole blood is often the only available specimen collected during such investigations, yet few studies have examined relationships between cannabis effects and whole blood concentrations following cannabis smoking. Nine male and one female heavy, chronic cannabis smokers resided on a closed research unit and smoked ad libitum one 6.8% THC cannabis cigarette. THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC were quantified in whole blood and plasma. Assessments were performed before and up to 6 h after smoking, including subjective [visual analog scales (VAS) and Likert scales], physiological (heart rate, blood pressure and respirations) and psychomotor (critical-tracking and divided-attention tasks) measures. THC significantly increased VAS responses and heart rate, with concentration-effect curves demonstrating counter-clockwise hysteresis. No significant differences were observed for critical-tracking or divided-attention task performance in this cohort of heavy, chronic cannabis smokers. The cannabis influence factor was not suitable for quantifying psychomotor impairment following cannabis consumption and was not precise enough to determine recent cannabis use with accuracy. These data inform our understanding of impairment and subjective effects following acute smoked cannabis and interpretation of whole blood cannabinoid concentrations in forensic investigations.

Sex Effects of Marijuana on Brain Structure and Function

OpenAIRE

Ketcherside, Ariel; Baine, Jessica; Filbey, Francesca

2016-01-01

Background Tetrahydrocannabinol (?9-THC), the primary ingredient in marijuana, exerts its effects across several neurological and biological systems that interact with the endocrine system. Thus, differential effects of ?9-THC are likely to exist based on sex and hormone levels. Methods We reviewed the existing literature to determine sex-based effects of ?9-THC on neural structure and functioning. Results The literature demonstrates differences in male and female marijuana users on brain str...

Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomised controlled crossover trial.

Science.gov (United States)

van den Elsen, Geke Ah; Tobben, Lieke; Ahmed, Amir Ia; Verkes, Robbert Jan; Kramers, Cornelis; Marijnissen, Radboud M; Olde Rikkert, Marcel Gm; van der Marck, Marjolein A

2017-02-01

Oral tetrahydrocannabinol (THC) is currently studied for its possible efficacy on dementia-related neuropsychiatric symptoms (NPS), but might lead to increased risk of falling. This was a randomised, double-blind, crossover study to evaluate the effects of THC on mobility in dementia patients. Eighteen community-dwelling patients ( M age =77 years) received 1.5 mg of oral THC twice daily and placebo, in random order, for three days, separated by a four-day washout. Balance and gait were assessed using SwayStar TM and GAITRite TM within two hours after administration, in two consecutive intervention periods, under the following conditions: standing with eyes open (EO) and eyes closed (EC), preferred speed walking with and without a cognitive dual task. THC significantly increased sway during standing EC (roll angle 0.32[±0.6]°, p=0.05; pitch angle 1.04[±1.5]°, p=0.009; pitch velocity 1.96[±3.3]°/s, p=0.02), but not during standing EO. During preferred speed walking, THC increased stride length (4.3[±5.4] cm, p=0.005) and trunk sway (pitch angle 1.18[±1.6]°, p=0.005). No effects were observed during dual task walking. No differences in the number and type of adverse events were found, and no falls occurred after administration of THC. This study showed that 3 mg of THC per day has a benign adverse event profile regarding mobility and was well tolerated by community-dwelling dementia patients.

In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

Energy Technology Data Exchange (ETDEWEB)

Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

1990-12-01

Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

Science.gov (United States)

Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

2015-09-01

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Decarboxylation of Δ 9-tetrahydrocannabinol: Kinetics and molecular modeling

Science.gov (United States)

Perrotin-Brunel, Helene; Buijs, Wim; van Spronsen, Jaap; van Roosmalen, Maaike J. E.; Peters, Cor J.; Verpoorte, Rob; Witkamp, Geert-Jan

2011-02-01

Efficient tetrahydrocannabinol (Δ 9-THC) production from cannabis is important for its medical application and as basis for the development of production routes of other drugs from plants. This work presents one of the steps of Δ 9-THC production from cannabis plant material, the decarboxylation reaction, transforming the Δ 9-THC-acid naturally present in the plant into the psychoactive Δ 9-THC. Results of experiments showed pseudo-first order reaction kinetics, with an activation barrier of 85 kJ mol -1 and a pre-exponential factor of 3.7 × 10 8 s -1. Using molecular modeling, two options were identified for an acid catalyzed β-keto acid type mechanism for the decarboxylation of Δ 9-THC-acid. Each of these mechanisms might play a role, depending on the actual process conditions. Formic acid proved to be a good model for a catalyst of such a reaction. Also, the computational idea of catalysis by water to catalysis by an acid, put forward by Li and Brill, and Churchev and Belbruno was extended, and a new direct keto-enol route was found. A direct keto-enol mechanism catalyzed by formic acid seems to be the best explanation for the observed activation barrier and the pre-exponential factor of the decarboxylation of Δ 9-THC-acid. Evidence for this was found by performing an extraction experiment with Cannabis Flos. It revealed the presence of short chain carboxylic acids supporting this hypothesis. The presented approach is important for the development of a sustainable production of Δ 9-THC from the plant.

Circulation and oxygen cycling in the Mediterranean Sea: Sensitivity to future climate change

Science.gov (United States)

Powley, Helen R.; Krom, Michael D.; Van Cappellen, Philippe

2016-11-01

Climate change is expected to increase temperatures and decrease precipitation in the Mediterranean Sea (MS) basin, causing substantial changes in the thermohaline circulation (THC) of both the Western Mediterranean Sea (WMS) and Eastern Mediterranean Sea (EMS). The exact nature of future circulation changes remains highly uncertain, however, with forecasts varying from a weakening to a strengthening of the THC. Here we assess the sensitivity of dissolved oxygen (O2) distributions in the WMS and EMS to THC changes using a mass balance model, which represents the exchanges of O2 between surface, intermediate, and deep water reservoirs, and through the Straits of Sicily and Gibraltar. Perturbations spanning the ranges in O2 solubility, aerobic respiration kinetics, and THC changes projected for the year 2100 are imposed to the O2 model. In all scenarios tested, the entire MS remains fully oxygenated after 100 years; depending on the THC regime, average deep water O2 concentrations fall in the ranges 151-205 and 160-219 µM in the WMS and EMS, respectively. On longer timescales (>1000 years), the scenario with the largest (>74%) decline in deep water formation rate leads to deep water hypoxia in the EMS but, even then, the WMS deep water remains oxygenated. In addition, a weakening of THC may result in a negative feedback on O2 consumption as supply of labile dissolved organic carbon to deep water decreases. Thus, it appears unlikely that climate-driven changes in THC will cause severe O2 depletion of the deep water masses of the MS in the foreseeable future.

Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease.

Science.gov (United States)

Valles-Ortega, Jordi; Duran, Jordi; Garcia-Rocha, Mar; Bosch, Carles; Saez, Isabel; Pujadas, Lluís; Serafin, Anna; Cañas, Xavier; Soriano, Eduardo; Delgado-García, José M; Gruart, Agnès; Guinovart, Joan J

2011-11-01

Lafora disease (LD) is caused by mutations in either the laforin or malin gene. The hallmark of the disease is the accumulation of polyglucosan inclusions called Lafora Bodies (LBs). Malin knockout (KO) mice present polyglucosan accumulations in several brain areas, as do patients of LD. These structures are abundant in the cerebellum and hippocampus. Here, we report a large increase in glycogen synthase (GS) in these mice, in which the enzyme accumulates in LBs. Our study focused on the hippocampus where, under physiological conditions, astrocytes and parvalbumin-positive (PV(+)) interneurons expressed GS and malin. Although LBs have been described only in neurons, we found this polyglucosan accumulation in the astrocytes of the KO mice. They also had LBs in the soma and some processes of PV(+) interneurons. This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function. Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD. Copyright © 2011 EMBO Molecular Medicine.

Weight History, Smoking, Physical Activity and Breast Cancer Risk among French-Canadian Women Non-Carriers of More Frequent BRCA1/2 Mutations

Directory of Open Access Journals (Sweden)

Vishnee Bissonauth

2009-01-01

Comparing cases to controls, breast cancer risk was higher among subjects who reached their maximum body mass index (BMI at an older age (>50 years (OR=2.83; 95% CI: 2.34–2.91. A positive association was noted between breast cancer risk and weight gain of >34 lbs compared to weight gain of ≤15 lbs, since the age of 20 (OR=1.68; 95% CI: 1.10–2.58. Weight gain of >24 lbs compared to weight gain of ≤9 lbs, since the age of 30 also resulted in the same relationship (OR=1.96; 95% CI: 1.46–3.06. Similarly, since the age of 40, weight gain of >12 lbs compared to weight gain of ≤1 lb was associated with increased breast cancer risk (OR=1.91; 95% CI: 1.53–2.66. Women who smoked >9 pack-years of cigarettes had a 59% higher breast cancer risk (P=.05. Subjects who engaged in >24.8 metabolic-equivalent- (MET- hours per week compared to ≤10.7 MET-hours per week of moderate physical activity had a 52% (P=.01 decreased risk and total physical activity between 16.2 and 33.2 MET-hours per week compared to ≤16.2 MET-hours per week, resulted in a 43% (P=.05 lower risk of breast cancer. In conclusion, weight history did affect breast cancer risk. Moreover, smoking appeared to raise the risk, whereas moderate physical activity had a protective effect.

Bounding estimate of DWPF mercury emissions

International Nuclear Information System (INIS)

Jacobs, R.A.

1993-01-01

Two factors which have substantial impact on predicted Mercury emissions are the air flows in the Chemical Process Cell (CPC) and the exit temperature of the Formic Acid Vent Condenser (FAVC). The discovery in the IDMS (Integrated DWPF Melter System) of H 2 generation by noble metal catalyzed formic acid decomposition and the resultant required dilution air flow has increased the expected instantaneous CPC air flow by as much as a factor of four. In addition, IDMS has experienced higher than design (10 degrees C) FAVC exit temperatures during certain portions of the operating cycle. These temperatures were subsequently attributed to the exothermic reaction of NO to NO 2 . Moreover, evaluation of the DWPF FAVC indicated it was undersized and unless modified or replaced, routine exit temperatures would be in excess of design. Purges required for H 2 flammability control and verification of elevated FAVC exit temperatures due to NO x reactions have lead to significant changes in CPC operating conditions. Accordingly, mercury emissions estimates have been updated based upon the new operating requirements, IDMS experience, and development of an NO x /FAVC model which predicts FAVC exit temperatures. Using very conservative assumptions and maximum purge rates, the maximum calculated Hg emissions is approximately 130 lbs/yr. A range of 100 to 120 lbs/yr is conservatively predicted for other operating conditions. The peak emission rate calculated is 0.027 lbs/hr. The estimated DWPF Hg emissions for the construction permit are 175 lbs/yr (0.02 lbs/hr annual average)

14 CFR Section 25 - Traffic and Capacity Elements

Science.gov (United States)

2010-01-01

... section 1-2 of this part, to use hardcopy data input forms or submit data via e-mail. Schedule T-8—Report... mail in scheduled and nonscheduled service; and (iii) Transport-related revenues. (2) Total operating... transported (F, G, L, N, P, R237)(in lbs). 13 63-72 10N Revenue mail transported (F, G, L, N, P, R239) (in lbs...

Characterization and potential recycling of home building wood waste

Science.gov (United States)

Philip A. Araman; D.P. Hindman; M.F. Winn

2010-01-01

Construction waste represents a significant portion of landfill waste, estimated as 17% of the total waste stream. Wood construction waste of a 2000 square foot single family home we found to be 1500-3700 lbs of solid-sawn wood, and 1000-1800 lbs of engineered wood products (EWP). Much of the solid-sawn lumber and EWPs could be recycled into several products. Through a...

Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of cannabinoids and phase I and II metabolites in meconium.

Science.gov (United States)

Prego-Meleiro, Pablo; Lendoiro, Elena; Concheiro, Marta; Cruz, Angelines; López-Rivadulla, Manuel; de Castro, Ana

2017-05-12

A liquid chromatography-tandem mass spectrometry (LC-MSMS) method was developed and fully validated for the determination of Δ 9 -tetrahydrocannabinol (THC), 11-hydroxyTHC (OHTHC), 11-nor-9-carboxyTHC (THCCOOH), 8-β-11-dihydroxyTHC (diOHTHC), cannabinol, cannabidiol, and THC and THCCOOH glucuronides in 0.25±0.02g meconium. Samples were homogenized in methanol and subjected to cation exchange solid-phase extraction. Chromatographic separation was performed on a Kinetex C18 column (50 mm×2.1mm, 2.6μm) at 35°C, with a gradient of 0.1% formic acid in water and acetonitrile at a flow rate of 0.3 mL/min; total run time was 10min. Two transitions per analyte were monitored in MRM mode. The method was specific and sensitive; LOD was from 1 to 2ng/g, and LOQ from 4 to 10ng/g; linearity ranged from 4 to 400 ng/g for all the analytes, except for THC glucuronide (10-400ng/g); intra-assay, inter-assay and total imprecision were <11.2%, <13.45% and <15.6%, respectively; accuracy ranged from 93.9% to 109.0% of the target concentration; matrix effect, extraction and process efficiency ranged from -26.4% to -71.4%, 49.9% to 69.5% and 14.3% to 45.0%, respectively. The inclusion of THC and THCCOOH glucuronides avoided the need for the hydrolysis process, thus facilitating sample pretreatment. Application of the method to 19 authentic meconium specimens from uncontrolled pregnancies or women suspicious of drug consumption revealed fetal cannabis exposure in 4 newborns. THCCOOH (24.1-288.8ng/g), diOHTHC (53.2-332.4ng/g), THC (4.2-7.7ng/g), CBN (30.7-93.3ng/g) and CBD (7.1-251.5ng/g) were detected in all cases; THCCOOH glucuronide (190.2-306.8ng/g) in 3 cases; and OHTHC (11.9ng/g) in the remaining one; however, THC glucuronide was not identified in any specimen. Copyright © 2017 Elsevier B.V. All rights reserved.

Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

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Darmani, N A

2001-01-01

We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1

Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity.

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M Paola Castelli

Full Text Available Methamphetamine (METH is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS, production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4 × 10 mg/kg, 2 hours apart were pre- or post-treated with Δ9-THC (1 or 3 mg/kg and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP. Results showed that, as compared to corresponding controls (i METH-induced nNOS overexpression in the caudate-putamen (CPu was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (-19% and -28% for 1 mg/kg pre- and post-treated animals; -25% and -21% for 3 mg/kg pre- and post-treated animals; (ii METH-induced GFAP-immunoreactivity (IR was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (-50% and by pre-treatment with 3 mg/kg Δ9-THC (-53%; (iii METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC by pre- and post-treatment with both doses of Δ9-THC (-34% and -47% for 1 mg/kg pre- and post-treated animals; -37% and -29% for 3 mg/kg pre- and post-treated animals. The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the PFC and CPu. Our

Intelligent Context-Aware and Adaptive Interface for Mobile LBS

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Jiangfan Feng

2015-01-01

Full Text Available Context-aware user interface plays an important role in many human-computer Interaction tasks of location based services. Although spatial models for context-aware systems have been studied extensively, how to locate specific spatial information for users is still not well resolved, which is important in the mobile environment where location based services users are impeded by device limitations. Better context-aware human-computer interaction models of mobile location based services are needed not just to predict performance outcomes, such as whether people will be able to find the information needed to complete a human-computer interaction task, but to understand human processes that interact in spatial query, which will in turn inform the detailed design of better user interfaces in mobile location based services. In this study, a context-aware adaptive model for mobile location based services interface is proposed, which contains three major sections: purpose, adjustment, and adaptation. Based on this model we try to describe the process of user operation and interface adaptation clearly through the dynamic interaction between users and the interface. Then we show how the model applies users’ demands in a complicated environment and suggested the feasibility by the experimental results.

Intelligent Context-Aware and Adaptive Interface for Mobile LBS.

Science.gov (United States)

Feng, Jiangfan; Liu, Yanhong

2015-01-01

Context-aware user interface plays an important role in many human-computer Interaction tasks of location based services. Although spatial models for context-aware systems have been studied extensively, how to locate specific spatial information for users is still not well resolved, which is important in the mobile environment where location based services users are impeded by device limitations. Better context-aware human-computer interaction models of mobile location based services are needed not just to predict performance outcomes, such as whether people will be able to find the information needed to complete a human-computer interaction task, but to understand human processes that interact in spatial query, which will in turn inform the detailed design of better user interfaces in mobile location based services. In this study, a context-aware adaptive model for mobile location based services interface is proposed, which contains three major sections: purpose, adjustment, and adaptation. Based on this model we try to describe the process of user operation and interface adaptation clearly through the dynamic interaction between users and the interface. Then we show how the model applies users' demands in a complicated environment and suggested the feasibility by the experimental results.

PVC makers study expansions to meet demand growth

International Nuclear Information System (INIS)

Hunter, D.; Coeyman, M.

1993-01-01

As prospects for the polyvinyl chloride (PVC) industry continue to improve, the next batch of capacity increases is being studied. Vista Chemical (Houston) sees an opportunity to achieve what company president James R. Ball calls the lowest-cost capacity addition in the market, by debottlenecking its PVC plants at Aberdeen, MS and Oklahoma City. That would increase capacity 40%, adding 300 million lbs/year to Vista's 830 million lbs/year. US demand for PVC grew 12.5% through the first 10 months of 1992, to 7.3 billion lbs, according to the latest figures available from the Society of the Plastics Industry. Alan Bailey, Oxy-Chem's executive v.p./polymers and plastics, predicts a good demand year in 1993 - better even than 1992, driven by an upward trend in housing starts and a recovering economy

Engineering assessment of 105 K basin monorails

International Nuclear Information System (INIS)

Frier, W.A.

1995-01-01

The engineering assessment of the 105 K Basins monorails was performed to provide the engineering analysis to justify the existing basin north-south monorail capacity. The existing monorails have a capacity of 2400 lbs posted on the north-south monorails. The engineering assessment concluded that the monorail, hanger system, and trolleys all rate for a 2000 lb capacity. Based upon a 2,500 lb trolley load, the monorails, the hanger system, and the double trolley hoist system will rate for 2,500 lbs. The single trolley hoist system for handling the fuel canisters and the trolley systems used in the various transfer areas are limited by manufacturers to 2,000 lbs. Therefore, it is concluded from this engineering assessment that the 2,400 lb capacity posting for the north-south basin monorails is appropriate

Influence of tetrahydrocurcumin on tail tendon collagen contents and its properties in rats with streptozotocin-nicotinamide-induced type 2 diabetes.

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Pari, Leelavinothan; Murugan, Pidaran

2007-12-01

Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late-stage complications in diabetics. Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, exhibiting many of the same physiological and pharmacological activities of curcumin and in some systems may exert greater antioxidant activity than curcumin. In diabetic rats, hydroxyproline and collagen content as well as its degree of cross-linking were increased, as shown by increased extent of glycation, collagen-linked fluorescence, neutral salt collagen, and decreased acid and pepsin solubility. Administration of THC for 45 days to diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effects of THC were comparable with those of curcumin. In conclusion, administration of THC had a positive influence on the content of collagen and its properties in streptozotocin- and nicotinamide-induced diabetic rats. THC was found to be more effective than curcumin.

The Plant-Derived Chalcone 2,2′,5′-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia

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Manasi Jiwrajka

2016-01-01

Full Text Available Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2′,5′-trihydroxychalcone (225THC, a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2′,5′-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions.

Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

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Júlia T. Novaes

2017-10-01

Full Text Available Tetrahydrocurcumin (THC, curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa. Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC activity, histone acetyltransferase (HAT activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

Influence of regenerative heat treatment on structure and properties of G20CrMo2 - 5 (L20HM cast steel

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G. Golański

2008-03-01

Full Text Available Thc papcr prcscnts rcsuSts or rcscarch on thc influence of rcgcncratic hcat treatment on thc structurc and propcrtics [hardncss. impactcncrgy or L2O11M cnst stccl. Invcstipatcd material was taken from outer fmmc of a turbinc which was scrviccd for t 67 424 hours a! thctcmpcrauirc or 535 "C and prcssurc or 12.75 MPa. In psi-operating condition ~hicnv cstigntcd cast steel was cl~aracteri~cbdy low impactcncrpy of II I ant1 hart3ncss of 139HV30. Analysis uF the irlflue~~uuel ;lustcniriz;~ti on pariimctcrs (tcrnpcr;lturc and lime has rcvealcd rhntat thc tcinpcr;~turcr angc o f 895 + 955 "C (i-e. h3 - +I IO + 70 "C.fo r both 3 and 5 hours of holtl timc. rhc ohtaincd grain sizc amounls to 20+ 2511m. I has hccn pmved that tempcred bainitic-rcrri~ica nd remit ic-hainiric-pearlit ic stn~cturco f thc invcstigatcd cast stccl msurcs highimpact cncrgy, i.c. KV > 1001. as well a5 hardncss. i.e. 11Y30. just at thc tcrnpcmturc of OXl "C. 'I'crnpcmliirc or 7110 "C causcs i'~tnhcrincrclrsc of impact cncrgy along with a slight dccrcasc of hardncss. Morcovcr. it has hccn concludd that nppl ying oS under-annealinginstcad or tcmpcring. nflcr standardizalion. guarantees scquircd impact cncrgy of KY r 271.

Detecting biomarkers of secondhand marijuana smoke in young children.

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Wilson, Karen M; Torok, Michelle R; Wei, Binnian; Wang, Lanqing; Robinson, Michelle; Sosnoff, Connie S; Blount, Benjamin C

2017-04-01

The impact of secondhand marijuana smoke exposure on children is unknown. New methods allow detection of secondhand marijuana smoke in children. We studied children ages 1 mo to 2 y hospitalized with bronchiolitis in Colorado from 2013 to 2015. Parents completed a survey, and urine samples were analyzed for cotinine using LC/MS/MS (limits of detection 0.03 ng/ml) and marijuana metabolites including COOH-THC (limits of detection 0.015 ng/ml). A total of 43 subjects had urine samples available for analysis. Most (77%) of the subjects were male, and 52% were less than 1 y of age. COOH-THC was detectable in 16% of the samples analyzed (THC+); the range in COOH-THC concentration was 0.03-1.5 ng/ml. Two subjects had levels >1 ng/ml. Exposure did not differ by gender or age. Non-white children had more exposure than white children (44 vs. 9%; P 2.0 ng/ml were THC+, compared with 7% of those with lower cotinine (P marijuana smoke can be detected in children; in this cohort, 16% were exposed. Detectable COOH-THC is more common in children with tobacco smoke exposure. More research is needed to assess the health impacts of marijuana smoke exposure on children and inform public health policy.

Δ9-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling

International Nuclear Information System (INIS)

Takeda, Shuso; Yamaori, Satoshi; Motoya, Erina; Matsunaga, Tamihide; Kimura, Toshiyuki; Yamamoto, Ikuo; Watanabe, Kazuhito

2008-01-01

We recently reported that Δ 9 -tetrahydrocannabinol (Δ 9 -THC) has the ability to stimulate the proliferation of human breast carcinoma MCF-7 cells. However, the mechanism of action remains to be clarified. The present study focused on the relationship between receptor expression and the effects of Δ 9 -THC on cell proliferation. RT-PCR analysis demonstrated that there was no detectable expression of CB receptors in MCF-7 cells. In accordance with this, no effects of cannabinoid 1/2 (CB1/2) receptor antagonists and pertussis toxin on cell proliferation were observed. Although MCF-7 cell proliferation is suggested to be suppressed by Δ 9 -THC in the presence of CB receptors, it was revealed that Δ 9 -THC could exert upregulation of living cells in the absence of the receptors. Interestingly, Δ 9 -THC upregulated human epithelial growth factor receptor type 2 (HER2) expression, which is known to be a predictive factor of human breast cancer and is able to stimulate cancer cells as well as MCF-7 cells. Actinomycin D-treatment interfered with the upregulation of HER2 and cell proliferation by cannabinoid. Taken together, these studies suggest that, in the absence of CB receptors, Δ 9 -THC can stimulate the proliferation of MCF-7 cells by modulating, at least in part, HER2 transcription

Genetic dissection of behavioural and autonomic effects of Delta(9-tetrahydrocannabinol in mice.

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Krisztina Monory

2007-10-01

Full Text Available Marijuana and its main psychotropic ingredient Delta(9-tetrahydrocannabinol (THC exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1, which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release gamma aminobutyric acid, cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.

Atomic orbital-based SOS-MP2 with tensor hypercontraction. II. Local tensor hypercontraction

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Song, Chenchen; Martínez, Todd J.

2017-01-01

In the first paper of the series [Paper I, C. Song and T. J. Martinez, J. Chem. Phys. 144, 174111 (2016)], we showed how tensor-hypercontracted (THC) SOS-MP2 could be accelerated by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs). This reduced the formal scaling of the SOS-MP2 energy calculation to cubic with respect to system size. The computational bottleneck then becomes the THC metric matrix inversion, which scales cubically with a large prefactor. In this work, the local THC approximation is proposed to reduce the computational cost of inverting the THC metric matrix to linear scaling with respect to molecular size. By doing so, we have removed the primary bottleneck to THC-SOS-MP2 calculations on large molecules with O(1000) atoms. The errors introduced by the local THC approximation are less than 0.6 kcal/mol for molecules with up to 200 atoms and 3300 basis functions. Together with the graphical processing unit techniques and locality-exploiting approaches introduced in previous work, the scaled opposite spin MP2 (SOS-MP2) calculations exhibit O(N2.5) scaling in practice up to 10 000 basis functions. The new algorithms make it feasible to carry out SOS-MP2 calculations on small proteins like ubiquitin (1231 atoms/10 294 atomic basis functions) on a single node in less than a day.

Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury

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Edith Hochhauser

2015-07-01

Full Text Available Background/Aims: Ischemia/reperfusion (I/R injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC, a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70% ischemia for 60min followed by reperfusion for 6 hours. Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway, the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation. This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.

A selective review of medical cannabis in cancer pain management.

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Blake, Alexia; Wan, Bo Angela; Malek, Leila; DeAngelis, Carlo; Diaz, Patrick; Lao, Nicholas; Chow, Edward; O'Hearn, Shannon

2017-12-01

Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to

Analytical gradients for tensor hyper-contracted MP2 and SOS-MP2 on graphical processing units

Science.gov (United States)

Song, Chenchen; Martínez, Todd J.

2017-10-01

Analytic energy gradients for tensor hyper-contraction (THC) are derived and implemented for second-order Møller-Plesset perturbation theory (MP2), with and without the scaled-opposite-spin (SOS)-MP2 approximation. By exploiting the THC factorization, the formal scaling of MP2 and SOS-MP2 gradient calculations with respect to system size is reduced to quartic and cubic, respectively. An efficient implementation has been developed that utilizes both graphics processing units and sparse tensor techniques exploiting spatial sparsity of the atomic orbitals. THC-MP2 has been applied to both geometry optimization and ab initio molecular dynamics (AIMD) simulations. The resulting energy conservation in micro-canonical AIMD demonstrates that the implementation provides accurate nuclear gradients with respect to the THC-MP2 potential energy surfaces.

The effect of cannabis on regular cannabis consumers' ability to ride a bicycle.

Science.gov (United States)

Hartung, Benno; Schwender, Holger; Roth, Eckhard H; Hellen, Florence; Mindiashvili, Nona; Rickert, Annette; Ritz-Timme, Stefanie; Grieser, Almut; Monticelli, Fabio; Daldrup, Thomas

2016-05-01

To assess the effects of cannabis on the ability required to ride a bicycle, repetitive practical cycling tests and medical examinations were carried out before and after inhalative consumption of cannabis. A maximum of three joints with body weight-adapted THC content (300 μg THC per kg body weight) could be consumed by each test subject. Fourteen regular cannabis-consuming test subjects were studied (12 males, 2 females). In summary, only a few driving faults were observed even under the influence of very high THC concentrations. A defined THC concentration that leads to an inability to ride a bicycle cannot be presented. The test subjects showed only slight distinctive features that can be documented using a medical test routinely run for persons under suspicion of driving under the influence of alcohol or drugs.

DECOVALEX-THMC Task D: Long-Term Permeability/Porosity Changes in the EDZ and Near Field due to THM and THC Processes in Volcanic and Crystalline-Bentonite Systems, Status Report October 2005

International Nuclear Information System (INIS)

Birkholzer, J.; Rutqvist, J.; Sonnenthal, E.; Barr, D.

2005-01-01

The DECOVALEX project is an international cooperative project initiated by SKI, the Swedish Nuclear Power Inspectorate, with participation of about 10 international organizations. The name DECOVALEX stands for DEvelopment of COupled models and their VALidation against Experiments. The general goal of this project is to encourage multidisciplinary interactive and cooperative research on modeling coupled processes in geologic formations in support of the performance assessment for underground storage of radioactive waste. Three multi-year project stages of DECOVALEX have been completed in the past decade, mainly focusing on coupled thermal-hydrological-mechanical processes. Currently, a fourth three-year project stage of DECOVALEX is under way, referred to as DECOVALEX-THMC. THMC stands for Thermal, Hydrological, Mechanical, and Chemical processes. The new project stage aims at expanding the traditional geomechanical scope of the previous DECOVALEX project stages by incorporating geochemical processes important for repository performance. The U.S. Department of Energy (DOE) leads Task D of the new DECOVALEX phase, entitled ''Long-term Permeability/Porosity Changes in the EDZ and Near Field due to THC and THM Processes for Volcanic and Crystalline-Bentonite Systems''. In its leadership role for Task D, DOE coordinates and sets the direction for the cooperative research activities of the international research teams engaged in Task D

Privacy vs. Reward in Indoor Location-Based Services

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Fawaz Kassem

2016-10-01

Full Text Available With the advance of indoor localization technology, indoor location-based services (ILBS are gaining popularity. They, however, accompany privacy concerns. ILBS providers track the users’ mobility to learn more about their behavior, and then provide them with improved and personalized services. Our survey of 200 individuals highlighted their concerns about this tracking for potential leakage of their personal/private traits, but also showed their willingness to accept reduced tracking for improved service. In this paper, we propose PR-LBS (Privacy vs. Reward for Location-Based Service, a system that addresses these seemingly conflicting requirements by balancing the users’ privacy concerns and the benefits of sharing location information in indoor location tracking environments. PR-LBS relies on a novel location-privacy criterion to quantify the privacy risks pertaining to sharing indoor location information. It also employs a repeated play model to ensure that the received service is proportionate to the privacy risk. We implement and evaluate PR-LBS extensively with various real-world user mobility traces. Results show that PR-LBS has low overhead, protects the users’ privacy, and makes a good tradeoff between the quality of service for the users and the utility of shared location data for service providers.

International Space Station Temperature and Humidity Control Subsystem Verification for Node 1

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Williams, David E.

2007-01-01

The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Supply (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper provides a summary of the nominal operation of the Node 1 THC subsystem design. The paper will also provide a discussion of the detailed Element Verification methodologies for nominal operation of the Node 1 THC subsystem operations utilized during the Qualification phase.

China’s Rare Earth Elements Industry: What Can the West Learn?

Science.gov (United States)

2010-03-01

Society of Rare Earths, “Every ton of rare earth produced, generates approximately 8.5 kilograms (18.7 lbs) of fluorine and 13 kilograms (28.7 lbs...Chinese Pay Toxic Price for a Green World,” Timesonline, December 6, 2009. 24 and support leading domestic producers like Baogang, Minmetals, and...introduced in lasers for medical and dental uses because they are suited to energy delivery without thermal build up in human tissue. Erbium is used

In Situ Wetland Restoration Demonstration

Science.gov (United States)

2014-07-28

Printed on recycled paper Approved for public release; distribution is unlimited. CONTRACT REPORT CR-NAVFAC-EXWC-1601 JUNE 2016 FINAL REPORT...obtained for SediMite TM deployment. The SediMite TM was deployed using a turf spreader for the coarse application and a Vortex for touch-up. The...application rate, using a Vortex spreader , was 10 lbs/minute, and the turf spreader was 150 lbs/min. Powdered Activated Carbon Slurry The field

Recovery and Stability of Δ9-Tetrahydrocannabinol Using the Oral-Eze® Oral Fluid Collection System and Intercept® Oral Specimen Collection Device.

Science.gov (United States)

Samano, Kimberly L; Anne, Lakshmi; Johnson, Ted; Tang, Kenneth; Sample, R H Barry

2015-10-01

Oral fluid (OF) is increasingly used for clinical, forensic and workplace drug testing as an alternative to urine. Uncertainties surrounding OF collection device performance, drug stability and testing reproducibility may be partially responsible for delays in the implementation of OF testing in regulated drug testing programs. Stability of Δ(9)-tetrahydrocannabinol (THC) fortified and authentic specimens was examined after routine collection, transport and laboratory testing. Acceptable recovery and stability were observed when THC-fortified OF (1.5 and 4.5 ng/mL) was applied to Oral-Eze devices. Neat OF samples collected with Oral-Eze, processed per the package insert, and fortified with THC (3 and 6 ng/mL) were stable (±20%) at room temperature (21-25°C), refrigerated (2-8°C) and frozen (-25 to -15°C) conditions up to 1 month, while samples collected with Intercept devices showed decreases at refrigerated and room temperatures. After long-term refrigerated or frozen storage, maximum reductions in THC concentrations were 42% for Oral-Eze and 69% for Intercept. After ≥1 year frozen storage, 80.7% of laboratory specimens positive for THC (3 ng/mL cut-off) by GC-MS were reconfirmed positive (within 25%), with an average THC decrease of 4.2%. Specimens (n = 47) processed with Oral-Eze (diluted) and tested via enzyme immunoassay were concordant with LC-MS-MS results and showed 100% sensitivity and 95% specificity. Paired specimens collected with Oral-Eze and Intercept exhibited 98% overall agreement between the immunoassay test systems. Collectively, these data demonstrate consistent and reproducible recovery and stability of THC in OF after collection, transport and laboratory testing using the Oral-Eze OF Collection System. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Just say 'know': how do cannabinoid concentrations influence users' estimates of cannabis potency and the amount they roll in joints?

Science.gov (United States)

Freeman, Tom P; Morgan, Celia J A; Hindocha, Chandni; Schafer, Gráinne; Das, Ravi K; Curran, H Valerie

2014-10-01

(1) To determine whether measured concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in individuals' own cannabis predict their estimates of drug potency and actual titration; and (2) to ascertain if these effects are influenced by frequency of use and cannabis type. Cross-sectional, naturalistic. Participants' own homes. A total of 247 cannabis users in the United Kingdom: 152 'recreational' (1-24 days/month) and 95 'daily' (≥25 days/month). Participants rated their own cannabis for its potency (1-10) and type ('resin', 'herbal', 'skunk') before smoking it in front of the researcher. The amount of cannabis (g) used in their joints was recorded and an additional sample was analysed for THC and CBD concentrations (%). THC concentrations were related negatively to the amount of cannabis used [unstandardized regression coefficient: b = -0.009, 95% confidence interval (CI) = -0.017, -0.002]. Potency estimates were predicted by increasing THC (b = 0.055, 95% CI = 0.020, 0.090) and decreasing CBD (b = -0.160, 95% CI = -0.284, -0.062), and both of these associations were mediated by cannabis type (THC: b = 0.018, 95% CI = 0.006, 0.037; CBD: b = -0.105, 95% CI = -0.198, -0.028). Potency estimates were more reflective of THC as frequency of use increased (b = 0.004, 95% CI = 0.001, 0.007) and were 7.3 times more so in daily (partial r = 0.381) than recreational users (r = 0.052). When using their own cannabis in a naturalistic setting, people titrate the amount they roll in joints according to concentrations of delta-9-tetrahydrocannabinol (THC) but not cannabidiol (CBD). Recreational users thus show poor understanding of cannabis potency. © 2014 Society for the Study of Addiction.

Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9-Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users

Directory of Open Access Journals (Sweden)

Hasan O. Keles

2017-10-01

Full Text Available Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis on prefrontal cortex (PFC function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13 performed a working memory task (n-back during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20–50 mg. Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO concentration after THC administration in several channels on the PFC during both the high working memory load (2-back and the low working memory load (0-back condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS.

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells

Science.gov (United States)

Sido, Jessica M.; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

2015-01-01

Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression. Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts. To this end, we studied HvGD by injecting H-2k splenocytes into H-2b mice and analyzing the immune response in the draining ingLNs. THC treatment significantly reduced T cell proliferation and activation in draining LNs of the recipient mice and decreased early stage rejection-indicator cytokines, including IL-2 and IFN-γ. THC treatment also increased the allogeneic skin graft survival. THC treatment in HvGD mice led to induction of MDSCs. Using MDSC depletion studies as well as adoptive transfer experiments, we found that THC-induced MDSCs were necessary for attenuation of HvGD. Additionally, using pharmacological inhibitors of CB1 and CB2 receptors and CB1 and CB2 knockout mice, we found that THC was working preferentially through CB1. Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection. PMID:26034207

Delta-9-tetrahydrocannabinol-induced dopamine release as a function of psychosis risk: 18F-fallypride positron emission tomography study.

Directory of Open Access Journals (Sweden)

Rebecca Kuepper

Full Text Available Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and (18F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ(9-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis. In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ(9-THC was measured in 9 healthy cannabis users (average risk psychotic disorder, 8 patients with psychotic disorder (high risk psychotic disorder and 7 un-related first-degree relatives (intermediate risk psychotic disorder. PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM, which accounts for time-dependent changes in (18F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ(9-THC administration, reflecting dopamine release. While Δ(9-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ(9-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ(9-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.

Simulation of the inhibition of water α-radiolysis via H2 addition

International Nuclear Information System (INIS)

Lertnaisat, Phantira; Katsumura, Yosuke; Mukai, Satoru; Umehara, Ryuji; Shimizu, Yuichi; Suzuki, Masashi

2014-01-01

The continuous formation of H 2 , O 2 , and H 2 O 2 observed in water during α-radiolysis may be suppressed by the addition of H 2 above the threshold hydrogen concentration (THC). Using the FACSIMILE simulation code, water radiolysis was reproduced in order to determine the THC and clarify the mechanism at room temperature. Using the reaction set and rate constants reported by Ershov and Gordeev together with the primary yields for water decomposition products generated using 12 MeV α-particles, the THC was found to be 165 μM. Further simulation results clearly showed that the value of THC is strongly dependent on the reaction set and rate constants. In addition, a possible mechanism involving a chain reaction governed by the two reactions OH + H 2 → H + H 2 O and H + H 2 O 2 → OH + H 2 O was proposed. Furthermore, the same inhibition effect was found when a high-temperature simulation (300degC) was performed, but the concentration range and THC were much smaller than the values obtained at room temperature. The importance of the reverse reaction OH + H 2 → H + H 2 O was also investigated. (author)

Long term stability of cannabis resin and cannabis extracts

DEFF Research Database (Denmark)

Lindholst, Christian

2010-01-01

at room temperature, 4 °C and - 20 °C for up to 4 years. Acidic THC degrades exponentially via decarboxylation with concentration halve-lives of approximately 330 and 462 days in daylight and darkness, respectively. The degradation of neutral THC seems to occur somewhat slower. When cannabinoids were...... stored in extracted form at room temperature the degradation rate of acidic THC increased significantly relative to resin material with concentration halve-lives of 35 and 91 days in daylight and darkness, respectively. Once cannabis material is extracted into organic solvents, care should be taken...

Study of the carbon reduction of thorium dioxide with the aid of high temperature X-ray diffractometry under controlled pressure, then under vacuum

International Nuclear Information System (INIS)

Pialoux, A.; Zaug, J.

1976-01-01

Compressed samples of various initial compositions in the range ThO 2 +nC(0 0 C. In this way, the lattice parameters of 'ThO 2 ' (fcc), 'ThC 2 ' (monoclinic, tetragonal and cubic forms) and 'ThC' (fcc) were measured and the compositions of these nonstoichiometric phases which coexist at high temperatures evaluated. Most of the thorium carbides observed contained, by all appearance, very little oxygen, and from this it was possible to refine some of the phase boundaries in the Th-C system previously established by some investigators. (Auth.)