THC and CBD in blood samples and seizures in Norway: Does CBD affect THC-induced impairment in apprehended subjects?

PubMed

Havig, Stine Marie; Høiseth, Gudrun; Strand, Maren Cecilie; Karinen, Ritva Anneli; Brochmann, Gerd-Wenche; Strand, Dag Helge; Bachs, Liliana; Vindenes, Vigdis

2017-07-01

Several publications have suggested increasing cannabis potency over the last decade, which, together with lower amounts of cannabidiol (CBD), could contribute to an increase in adverse effects after cannabis smoking. Naturalistic studies on tetrahydrocannabinol (THC) and CBD in blood samples are, however, missing. This study aimed to investigate the relationship between THC- and CBD concentrations in blood samples among cannabis users, and to compare cannabinoid concentrations with the outcome of a clinical test of impairment (CTI) and between traffic accidents and non-accident driving under the influence of drugs (DUID)-cases. Assessment of THC- and CBD contents in cannabis seizures was also included. THC- and CBD concentrations in blood samples from subjects apprehended in Norway from April 2013-April 2015 were included (n=6134). A CTI result was compared with analytical findings in cases where only THC and/or CBD were detected (n=705). THC- and CBD content was measured in 41 cannabis seizures. Among THC-positive blood samples, 76% also tested positive for CBD. There was a strong correlation between THC- and CBD concentrations in blood samples (Pearson's r=0.714, p<0.0005). Subjects judged as impaired by a CTI had significantly higher THC- (p<0.001) and CBD (p=0.008) concentrations compared with not impaired subjects, but after multivariate analyses, impairment could only be related to THC concentration (p=0.004). Analyzing seizures revealed THC/CBD ratios of 2:1 for hashish and 200:1 for marijuana. More than ¾ of the blood samples testing positive for THC, among subjects apprehended in Norway, also tested positive for CBD, suggesting frequent consumption of high CBD cannabis products. The simultaneous presence of CBD in blood does, however, not appear to affect THC-induced impairment on a CTI. Seizure sample analysis did not reveal high potency cannabis products, and while CBD content appeared high in hashish, it was almost absent in marijuana. Copyright �

47 CFR 0.381 - Defense Commissioner.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Defense Commissioner. 0.381 Section 0.381 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Delegations of Authority National Security and Emergency Preparedness Delegations § 0.381 Defense Commissioner. The authority...

47 CFR 0.381 - Defense Commissioner.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Defense Commissioner. 0.381 Section 0.381 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Delegations of Authority National Security and Emergency Preparedness Delegations § 0.381 Defense Commissioner. The authority...

Hair analysis for delta(9)-THC, delta(9)-THC-COOH, CBN and CBD, by GC/MS-EI. Comparison with GC/MS-NCI for delta(9)-THC-COOH.

PubMed

Baptista, Maria João; Monsanto, Paula Verâncio; Pinho Marques, Estela Gouveia; Bermejo, Ana; Avila, Sofia; Castanheira, Alice Martelo; Margalho, Cláudia; Barroso, Mário; Vieira, Duarte Nuno

2002-08-14

A sensitive analytical method was developed for quantitative analysis of delta(9)-tetrahydrocannabinol (delta(9)-THC), 11-nor-delta(9)-tetrahydrocannabinol-carboxylic acid (delta(9)-THC-COOH), cannabinol (CBN) and cannabidiol (CBD) in human hair. The identification of delta(9)-THC-COOH in hair would document Cannabis use more effectively than the detection of parent drug (delta(9)-THC) which might have come from environmental exposure. Ketamine was added to hair samples as internal standard for CBN and CBD. Ketoprofen was added to hair samples as internal standard for the other compounds. Samples were hydrolyzed with beta-glucuronidase/arylsulfatase for 2h at 40 degrees C. After cooling, samples were extracted with a liquid-liquid extraction procedure (with chloroform/isopropyl alcohol, after alkalinization, and n-hexane/ethyl acetate, after acidification), which was developed in our laboratory. The extracts were analysed before and after derivatization with pentafluoropropionic anhydride (PFPA) and pentafluoropropanol (PFPOH) using a Hewlett Packard gas chromatographer/mass spectrometer detector, in electron impact mode (GC/MS-EI). Derivatized delta(9)-THC-COOH was also analysed using a Hewlett Packard gas chromatographer/mass spectrometer detector, in negative ion chemical ionization mode (GC/MS-NCI) using methane as the reagent gas. Responses were linear ranging from 0.10 to 5.00 ng/mg hair for delta(9)-THC and CBN, 0.10-10.00 ng/mg hair for CBD, 0.01-5.00 ng/mg for delta(9)-THC-COOH (r(2)>0.99). The intra-assay precisions ranged from <0.01 to 12.40%. Extraction recoveries ranged from 80.9 to 104.0% for delta(9)-THC, 85.9-100.0% for delta(9)-THC-COOH, 76.7-95.8% for CBN and 71.0-94.0% for CBD. The analytical method was applied to 87 human hair samples, obtained from individuals who testified in court of having committed drug related crimes. Quantification of delta(9)-THC-COOH using GC/MS-NCI was found to be more convenient than GC/MS-EI. The latter may give rise

40 CFR 1065.660 - THC and NMHC determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false THC and NMHC determination. 1065.660... CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.660 THC and NMHC determination. (a) THC determination and THC/CH 4 initial contamination corrections. (1) If we require you to...

THC Prevents MDMA Neurotoxicity in Mice.

PubMed

Touriño, Clara; Zimmer, Andreas; Valverde, Olga

2010-02-10

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4) were pretreated with THC (3 mg/kg x 4) at room (21 degrees C) and at warm (26 degrees C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1) receptor antagonist AM251 and the CB(2) receptor antagonist AM630, as well as in CB(1), CB(2) and CB(1)/CB(2) deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1) receptor antagonist AM251, neither in CB(1) and CB(1)/CB(2) knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2) cannabinoid antagonist and in CB(2) knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1) receptor, although CB(2) receptors may also contribute to

THC Prevents MDMA Neurotoxicity in Mice

PubMed Central

Touriño, Clara; Zimmer, Andreas; Valverde, Olga

2010-01-01

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg ×4) were pretreated with THC (3 mg/kg ×4) at room (21°C) and at warm (26°C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB1 receptor antagonist AM251 and the CB2 receptor antagonist AM630, as well as in CB1, CB2 and CB1/CB2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB1 receptor antagonist AM251, neither in CB1 and CB1/CB2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB2 cannabinoid antagonist and in CB2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB1 receptor, although CB2 receptors may also contribute to attenuate neuroinflammation in this

Separate and combined effects of the GABAB agonist baclofen and Δ9-THC in humans discriminating Δ9-THC

PubMed Central

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

2012-01-01

Background Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ9-THC. The aim of the present study was to determine the potential involvement of the GABAB receptor subtype by assessing the separate and combined effects of the GABAB-selective agonist baclofen and Δ9-THC using pharmacologically specific drug-discrimination procedures. Methods Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received baclofen (25 and 50 mg), Δ9-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results Δ9-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50 mg) substituted for the Δ9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ9-THC-like subjective responses when administered alone. Conclusions These results suggest that the GABAB receptor subtype is involved in the abuse-related effects of Δ9-THC, and that GABAB receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABAA) to determine the contribution of the different GABA receptors in the effects of Δ9-THC, and by extension cannabis, in humans. PMID:22699093

Public policy involvement by health commissioners.

PubMed

Thompson, Amy; Boardley, Debra; Kerr, Dianne; Greene, Tiffany; Jenkins, Melissa

2009-08-01

The purpose of this national study was to determine advocacy activities and level of involvement of health commissioners regarding public policy. Benefits, barriers, and perceived outcomes of advocacy efforts were also explored. A previously validated (Holtrop et al., Am J Health Behav 24(2):132-142, 2000) four-page survey was mailed to 700 health commissioners, who were randomly selected from the National Association of County and City Health Officials (NACCHO) database. A three-wave mailing was performed which yielded a 50% response rate. Of these respondents, the majority (70%) were female and (88%) Caucasian. Overall, 31% of health commissioners reported being involved in influencing public policy in the last 4 years. The most common reported activities engaged in by health commissioners included voting (84%), and providing policy information to consumers or other professionals (77%). Perceived barriers to influencing policy were time, (64%), and other priorities (46%). Perceived benefits to influencing policy included improving the health of the public (94%) and making a difference in others' lives (87%). Only 15% perceived their knowledge regarding the process of changing public policy was excellent. Although health commissioners are often spokespersons for health agencies and communities, their public policy involvement is marginal. Professional preparation programs and continuing education opportunities should focus on advocacy, public policy development, and removing barriers to action.

Delta-9-tetrahydrocannabinol (THC) serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC.

PubMed

Hunault, Claudine C; Mensinga, Tjeert T; de Vries, Irma; Kelholt-Dijkman, Hermien H; Hoek, Jani; Kruidenier, Maaike; Leenders, Marianne E C; Meulenbelt, Jan

2008-12-01

Delta9-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). The pharmacokinetics of THC after smoking cannabis cigarettes containing more than approximately 35 mg THC (3.55% THC cigarettes) is unknown. To be able to perform suitable exposure risk analysis, it is important to know if there is a linear relation at higher doses. The present study aimed to characterise the pharmacokinetics of THC, the active metabolite 11-OH-THC and the inactive metabolite THC-COOH after smoking a combination of tobacco and cannabis containing high THC doses. This double-blind, placebo-controlled, four-way, cross-over study included 24 male non-daily cannabis users (two to nine joints per month). Participants were randomly assigned to smoke cannabis cigarettes containing 29.3, 49.1 and 69.4 mg THC and a placebo. Serial serum samples collected over a period of 0-8 h were analysed by liquid chromatography electrospray tandem mass spectrometry. Effects on heart rate, blood pressure and 'high' feeling were also measured. Mean maximal concentrations (Cmax) were 135.1, 202.9 and 231.0 microg/L for THC and 9.2, 16.4 and 15.8 microg/L for 11-OH-THC after smoking a 29.3-, 49.1- and 69.4-mg THC cigarette, respectively. A large inter-individual variability in Cmax was observed. Heart rate and 'high' feeling significantly increased with increasing THC dose. This study demonstrates that the known linear association between THC dose and THC serum concentration also applies for high THC doses.

24 CFR 203.320 - Notice and date of termination by Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Commissioner that title will not be conveyed to the Commissioner and a claim for the insurance benefits will... mortgagee, if the mortgagee notifies the Commissioner that title will not be conveyed to the Commissioner...

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

PubMed

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.

Validation of a two-dimensional gas chromatography mass spectrometry method for the simultaneous quantification of cannabidiol, Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC in plasma.

PubMed

Karschner, Erin L; Barnes, Allan J; Lowe, Ross H; Scheidweiler, Karl B; Huestis, Marilyn A

2010-05-01

A sensitive analytical method for simultaneous quantification of sub-nanogram concentrations of cannabidiol (CBD), Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) in plasma is presented for monitoring cannabinoid pharmacotherapy and illicit cannabis use. Analytes were extracted from 1 mL plasma by solid-phase extraction, derivatized with N,O-bis(trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane, and analyzed by two-dimensional gas chromatography mass spectrometry (2D-GCMS) with cryofocusing. The lower calibration curve was linear from 0.25-25 ng/mL for CBD and THC, 0.125-25 ng/mL for 11-OH-THC and 0.25-50 ng/mL for THCCOOH. A second higher linear range from 5-100 ng/mL, achieved through modification of injection parameters, was validated for THC, 11-OH-THC, and THCCOOH and was only implemented if concentrations exceeded the lower curve upper limit of linearity. This procedure prevented laborious re-extraction by allowing the same specimen to be re-injected for quantification on the high calibration curve. Intra- and inter-assay imprecision, determined at four quality control concentrations, were or=72.9% for all analytes. Analytes were stable when stored at 22 degrees C for 16 h, 4 degrees C for 48 h, after three freeze-thaw cycles at -20 degrees C and when stored on the autosampler for 48 h. This sensitive and specific 2D-GCMS assay provides a new means of simultaneously quantifying CBD, THC and metabolite biomarkers in clinical medicine, forensic toxicology, workplace drug testing, and driving under the influence of drugs programs.

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

NASA Technical Reports Server (NTRS)

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.

47 CFR 0.181 - The Defense Commissioner.

Code of Federal Regulations, 2010 CFR

2010-10-01

... designated by the Commission. The Defense Commissioner directs the homeland security, national security and..., departments, or agencies. (c) To act as the Homeland Security and Defense Coordinator in representations with... emergency, the Defense Commissioner, in consultation with the Chief, Public Safety and Homeland Security...

47 CFR 0.181 - The Defense Commissioner.

Code of Federal Regulations, 2011 CFR

2011-10-01

... designated by the Commission. The Defense Commissioner directs the homeland security, national security and..., departments, or agencies. (c) To act as the Homeland Security and Defense Coordinator in representations with... emergency, the Defense Commissioner, in consultation with the Chief, Public Safety and Homeland Security...

47 CFR 0.181 - The Defense Commissioner.

Code of Federal Regulations, 2014 CFR

2014-10-01

... designated by the Commission. The Defense Commissioner directs the homeland security, national security and..., departments, or agencies. (c) To act as the Homeland Security and Defense Coordinator in representations with... emergency, the Defense Commissioner, in consultation with the Chief, Public Safety and Homeland Security...

47 CFR 0.181 - The Defense Commissioner.

Code of Federal Regulations, 2013 CFR

2013-10-01

... designated by the Commission. The Defense Commissioner directs the homeland security, national security and..., departments, or agencies. (c) To act as the Homeland Security and Defense Coordinator in representations with... emergency, the Defense Commissioner, in consultation with the Chief, Public Safety and Homeland Security...

47 CFR 0.181 - The Defense Commissioner.

Code of Federal Regulations, 2012 CFR

2012-10-01

... designated by the Commission. The Defense Commissioner directs the homeland security, national security and..., departments, or agencies. (c) To act as the Homeland Security and Defense Coordinator in representations with... emergency, the Defense Commissioner, in consultation with the Chief, Public Safety and Homeland Security...

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

PubMed

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.

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

PubMed

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.

PubMed

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

ERIC Educational Resources Information Center

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

P. Dixon

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 Reportmore » 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

Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration

PubMed Central

Karschner, EL; Darwin, WD; McMahon, RP; Liu, F; Wright, S; Goodwin, RS; Huestis, MA

2013-01-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and “good drug effects” with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses. PMID:21289620

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

NASA Astrophysics Data System (ADS)

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.

40 CFR 1065.660 - THC, NMHC, and CH4 determination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false THC, NMHC, and CH4 determination. 1065... POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.660 THC, NMHC, and CH4 determination. (a) THC determination and initial THC/CH 4 contamination corrections. (1) If we...

40 CFR 1065.660 - THC, NMHC, and CH4 determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false THC, NMHC, and CH4 determination. 1065... POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.660 THC, NMHC, and CH4 determination. (a) THC determination and initial THC/CH 4 contamination corrections. (1) If we...

40 CFR 1065.660 - THC, NMHC, and CH4 determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false THC, NMHC, and CH4 determination. 1065... POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.660 THC, NMHC, and CH4 determination. (a) THC determination and initial THC/CH 4 contamination corrections. (1) If we...

40 CFR 1065.660 - THC, NMHC, and CH4 determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 33 2011-07-01 2011-07-01 false THC, NMHC, and CH4 determination. 1065... POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Calculations and Data Requirements § 1065.660 THC, NMHC, and CH4 determination. (a) THC determination and THC/CH 4 initial contamination corrections. (1) If we...

Benthic ecological status of Algerian harbours.

PubMed

Dauvin, J C; Bakalem, A; Baffreau, A; Grimes, S

2017-12-15

This work is an overview of all available benthic data collected in the Algerian harbours between 1983 and 2001. So, total of 571 stations were reported in the 10 major Algerian harbours along the Algerian coast (1200km). Two main categories of harbours were distinguished according to their hydrodynamic regime and volume of water exchange between inner harbour basins and the entrance of the harbours. Univariate, multivariate, benthic indices and Biological Traits of Life approaches were applied on stations sampled in the late 1990s and long-term observations in six out of these ten harbours. These approaches assessed the main characteristics and ecological statuses from these south Mediterranean harbours. One of the main characteristics of the Algerian harbours was the very high species diversity (847 species). Although all the fauna was dominated by pollution-tolerant species; some harbours such as Bethioua and Djendjen hosted normal benthic communities as found in the open sea, but also included some pollution indicator species typical of a slight polluted system. On the contrary, the newly constructed port of Skikda showed perturbed benthic communities in relation to hydrocarbon pollution. Biological Traits of Life analysis reinforced the separation of benthic species along a gradient reflecting their sensitivity or tolerance to pollution. This response was related to an increase in organic matter content, probably associated with a general organic and metal contamination, from the entrance of the harbour to the innermost basins in areas with weak circulation, high sedimentation rate and concentrations of pollutants. Except for Oran harbour, where the poor to moderate ecological status remained unchanged with time, the other harbours showed an improvement or a slight degradation. A strategy of long-term monitoring should be promoted, based on a restricted and selected number of stations characteristic of the different basins and water masses occupying the

Subjective and physiological effects after controlled Sativex and oral THC administration.

PubMed

Karschner, E L; Darwin, W D; McMahon, R P; Liu, F; Wright, S; Goodwin, R S; Huestis, M A

2011-03-01

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

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.

PubMed

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.

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*

PubMed Central

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

2012-01-01

Background 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. Methods 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. Results Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5 h (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 1-5 h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5 h after the last THC dose, respectively. Conclusions 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. PMID:22464363

MDMA attenuates THC withdrawal syndrome in mice.

PubMed

Touriño, Clara; Maldonado, Rafael; Valverde, Olga

2007-07-01

3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Delta(9)-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. Both chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.

Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract.

PubMed

Nadulski, Thomas; Pragst, Fritz; Weinberg, Gordon; Roser, Patrik; Schnelle, Martin; Fronk, Eva-Maria; Stadelmann, Andreas Michael

2005-12-01

Cannabidiol (CBD) is known to modify the effects of Delta-tetrahydrocannabinol (THC) by decreasing anxiety and antagonizing other THC-effects. As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. In context of the use of cannabis-based medicine extracts for therapeutic purposes, a study was performed in a double-blind and placebo-controlled cross-over design in which each of 24 volunteers (12 male and 12 female, age 18-45 years) obtained soft-gelatin capsules with 10 mg THC (THC-set), cannabis extract containing 10 mg THC +5.4 mg CBD (CAN-set) or placebo in weekly intervals. Blood samples were taken 30 minutes before and 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 9 hours and 24 hours after the intake. The concentrations of THC, of its metabolites 11-OH-THC, THC-COOH and of CBD in the plasma samples were determined by automatic solid phase extraction, derivatization with N,O-bis(trimethylsilyl)triflouroacetamide and gas chromatography-mass spectrometry. The concentration versus time curves (maximum concentrations Cmax, corresponding time tmax and areas under the curves AUC) were evaluated by statistical methods with respect to equivalence or differences between the CAN-set and the THC-set. Furthermore, the intra-individual ratios of Cmax and AUC for 11-OH-THC/THC, THC-COOH/THC and THC-COOH/11-OH-THC were compared between the THC-set and the CAN-set. Despite the large variation of the data, evidence emerged from the total of the results that CBD partially inhibits the CYP 2C catalyzed hydroxylation of THC to 11-OH-THC. The probability for this inhibition is particularly high for oral intake because THC and CBD attain relatively high concentrations in the liver and because of the high first-pass metabolism of THC. However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at

17 CFR 140.11 - Emergency action by the senior Commissioner available.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Emergency action by the senior... the senior Commissioner available. (a) Authority of senior Commissioner. When it is not feasible to convene a quorum of the Commission, the Senior Commissioner present at the principal offices of the...

Properties of the Only Thorium Fullerene, Th@C84, Uncovered.

PubMed

Kaminský, Jakub; Vícha, Jan; Bouř, Petr; Straka, Michal

2017-04-27

Only a single thorium fullerene, Th@C 84 , has been reported to date (Akiyama, K.; et al. J. Nucl. Radiochem. Sci. 2002, 3, 151-154). Although the system was characterized by UV-vis and XANES (X-ray absorption near edge structure) spectra, its structure and properties remain unknown. In this work we used the density functional calculations to identify molecular and electronic structure of the Th@C 84 . Series of molecular structures satisfying the ThC 84 stoichiometric formula were studied comprising 24 IPR and 110 non-IPR Th@C 84 isomers as well as 9 ThC 2 @C 82 IPR isomers. The lowest energy structure is Th@C 84 -C s (10) with the singlet ground state. Its predicted electronic absorption spectra are in agreement with the experimentally observed ones. The bonding between the cage and Th was characterized as polar covalent with Th in formal oxidation state IV. The NMR chemical shifts of Th@C 84 -C s (10) were predicted to guide the future experimental efforts in identification of this compound.

21 CFR 570.15 - Adoption of regulation on initiative of Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adoption of regulation on initiative of Commissioner. 570.15 Section 570.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Adoption of regulation on initiative of Commissioner. (a) The Commissioner upon his own initiative may...

21 CFR 170.15 - Adoption of regulation on initiative of Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adoption of regulation on initiative of Commissioner. 170.15 Section 170.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Adoption of regulation on initiative of Commissioner. (a) The Commissioner upon his own initiative may...

Validated method for the simultaneous determination of Delta9-THC and Delta9-THC-COOH in oral fluid, urine and whole blood using solid-phase extraction and liquid chromatography-mass spectrometry with electrospray ionization.

PubMed

Teixeira, Helena; Verstraete, Alain; Proença, Paula; Corte-Real, Francisco; Monsanto, Paula; Vieira, Duarte Nuno

2007-08-06

A fully validated, sensitive and specific method for the extraction and quantification of Delta(9)-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Delta(9)-THC (THC-COOH) and for the detection of 11-hydroxy-Delta(9)-THC (11-OH THC) in oral fluid, urine and whole blood is presented. Solid-phase extraction and liquid chromatography-mass spectrometry (LC-MS) technique were used, with electrospray ionization. Three ions were monitored for THC and THC-COOH and two for 11-OH THC. The compounds were quantified by selected ion recording of m/z 315.31, 329.18 and 343.16 for THC, 11-OH THC and THC-COOH, respectively, and m/z 318.27 and 346.26 for the deuterated internal standards, THC-d(3) and THC-COOH-d(3), respectively. The method proved to be precise for THC and THC-COOH both in terms of intra-day and inter-day analysis, with intra-day coefficients of variation (CV) less than 6.3, 6.6 and 6.5% for THC in saliva, urine and blood, respectively, and 6.8 and 7.7% for THC-COOH in urine and blood, respectively. Day-to-day CVs were less than 3.5, 4.9 and 11.3% for THC in saliva, urine and blood, respectively, and 6.2 and 6.4% for THC-COOH in urine and blood, respectively. Limits of detection (LOD) were 2 ng/mL for THC in oral fluid and 0.5 ng/mL for THC and THC-COOH and 20 ng/mL for 11-OH THC, in urine and blood. Calibration curves showed a linear relationship for THC and THC-COOH in all samples (r(2)>0.999) within the range investigated. The procedure presented here has high specificity, selectivity and sensitivity. It can be regarded as an alternative method to GC-MS for the confirmation of positive immunoassay test results, and can be used as a suitable analytical tool for the quantification of THC and THC-COOH in oral fluid, urine and/or blood samples.

24 CFR 242.59 - Inspection of facilities by Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Inspection of facilities by Commissioner. 242.59 Section 242.59 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF...

Interactions between THC and cannabidiol in mouse models of cannabinoid activity.

PubMed

Varvel, S A; Wiley, J L; Yang, R; Bridgen, D T; Long, K; Lichtman, A H; Martin, B R

2006-06-01

Interest persists in characterizing potential interactions between Delta(9)-tetrahydocannabinol (THC) and other marijuana constituents such as cannabidiol (CBD). Such interactions may have important implications for understanding the long-term health consequences of chronic marijuana use as well as for attempts to develop therapeutic uses for THC and other CB(1) agonists. We investigated whether CBD may modulate the pharmacological effects of intravenously administered THC or inhaled marijuana smoke on hypoactivity, antinociception, catalepsy, and hypothermia, the well characterized models of cannabinoid activity. Intravenously administered CBD possessed very little activity on its own and, at a dose equal to a maximally effective dose of THC (3 mg/kg), failed to alter THC's effects on any measure. However, higher doses of CBD (ED(50)=7.4 mg/kg) dose-dependently potentiated the antinociceptive effects of a low dose of THC (0.3 mg/kg). Pretreatment with 30 mg/kg CBD, but not 3 mg/kg, significantly elevated THC blood and brain levels. No interactions between THC and CBD were observed in several variations of a marijuana smoke exposure model. Either quantities of CBD were applied directly to marijuana, CBD and THC were both applied to placebo plant material, or mice were pretreated intravenously with 30 mg/kg CBD before being exposed to marijuana smoke. As the amount of CBD found in most marijuana strains in the US is considerably less than that of THC, these results suggest that CBD concentrations relevant to what is normally found in marijuana exert very little, if any, modulatory effects on CB(1)-receptor-mediated pharmacological effects of marijuana smoke.

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

PubMed

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.

PubMed

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.

19 CFR 12.42 - Findings of Commissioner of Customs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Findings of Commissioner of Customs. 12.42 Section 12.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Labor § 12.42 Findings of Commissioner of Customs. (a) If any port director or other principal Customs...

19 CFR 12.42 - Findings of Commissioner of Customs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Findings of Commissioner of Customs. 12.42 Section 12.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Labor § 12.42 Findings of Commissioner of Customs. (a) If any port director or other principal Customs...

19 CFR 12.42 - Findings of Commissioner of Customs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Findings of Commissioner of Customs. 12.42 Section 12.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Labor § 12.42 Findings of Commissioner of Customs. (a) If any port director or other principal Customs...

19 CFR 12.42 - Findings of Commissioner of Customs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Findings of Commissioner of Customs. 12.42 Section 12.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Labor § 12.42 Findings of Commissioner of Customs. (a) If any port director or other principal Customs...

19 CFR 12.42 - Findings of Commissioner of Customs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Findings of Commissioner of Customs. 12.42 Section 12.42 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Labor § 12.42 Findings of Commissioner of Customs. (a) If any port director or other principal Customs...

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

PubMed

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.

Kinetic Algorithms for Harbour Management

NASA Astrophysics Data System (ADS)

Gold, C. M.; Goralski, R. I.

2012-07-01

Modern harbour management for a busy port needs to resolve a variety of simultaneous problems. Harbour traffic may be busy and the waterways congested, both by the major shipping and by the attendant harbour tugs. The harbour channel may be narrow and tortuous, and rapidly changing tides may require frequent course adjustments. Navigation aids must be clearly specified and immediately identifiable, in order to permit safe passage for the vessels. This requires a GIS with attributes not easily available with traditional products. The GeoVS system is a kinetic GIS with full three-dimensional visualisation, so that ships, bathymetry and landscape may be viewed in a form that is immediately understandable to both harbour pilots and the harbour authority. The system is kinetic because the data structures used to preserve the topological relationships between ships, seafloor and coastline are able to be maintained on a real-time basis, taking account of ship movement recorded on the compulsory AIS (Automatic Information System) beacons. Maintenance of this real-time topology allows for easy detection of potential collisions, as well as real-time bathymetric estimations, necessary to prevent ship grounding in highly tidal environments. The system, based on previous research into kinetic Voronoi diagrams, as well as development of a completely new graphical engine, is now in commercial production, where its advantages over simpler twodimensional models without automatic collision and grounding detection are becoming evident. Other applications are readily envisaged, and will be addressed in the near future.

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

PubMed

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

31 CFR 245.10 - Performance of functions of the Commissioner.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE CLAIMS ON ACCOUNT OF TREASURY CHECKS § 245.10 Performance of functions of the Commissioner. The Commissioner of the Financial... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Performance of functions of the...

21 CFR 16.44 - Communication to presiding officer and Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Communication to presiding officer and Commissioner. 16.44 Section 16.44 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Officer § 16.44 Communication to presiding officer and Commissioner. (a) Regulatory hearings are not...

The Commissioner's Annual Report: Submitted to the Congress by the Commissioner of Education in Accordance with Sec. 412. (b) of P. L. 91-230.

ERIC Educational Resources Information Center

Marland, S. P., Jr.

An accounting is made in this report of the work of the Office of the Commissioner of Education during Fiscal Year 1970 and reflects the state of American education today. The Commissioner envisions the Federal role in education to be one of increasing the effectiveness of the human and financial resources of our schools, colleges and…

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.

PubMed

Johnson, Jeremy R; Burnell-Nugent, Mary; Lossignol, Dominique; Ganae-Motan, Elena Doina; Potts, Richard; Fallon, Marie T

2010-02-01

This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids. Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

PubMed

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.

Has the intake of THC by cannabis users changed over the last decade? Evidence of increased exposure by analysis of blood THC concentrations in impaired drivers.

PubMed

Vindenes, Vigdis; Strand, Dag Helge; Kristoffersen, Lena; Boix, Fernando; Mørland, Jørg

2013-03-10

The main psychoactive substance, Δ9-tetrahydrocannabinol (THC) can be present in highly variable amounts in different cannabis preparations. An increase in THC content in cannabis products has been suggested, and reported from several countries. However, it has not yet been investigated if products with high potency lead to increased human exposure, and thus to higher risk of adverse effects. In this study, we examined the mean concentrations of THC in whole blood samples from drivers apprehended in Norway in the period between 2000 and 2010 suspected of driving under the influence of drugs. Cases with only THC (n=1747) have been compared to cases with only ethanol (n=38796) or amphetamines (n=2493). The increase in mean THC concentration measured from 2000 to 2010 was from 4.0 ± 0.3 to 6.6 ± 0.4 ng/ml (58%), compared to 3% for ethanol and 16% for the amphetamines. This increase in THC concentrations was to some extent paralleled by an increase in the percentage of drivers which were judged as lightly impaired by a physician. Monitoring concentrations of drugs of abuse in blood from apprehended drivers indicated an increasing exposure to THC in Norway. If similar trends are observed globally, it should be further explored if this type of information could be used to elucidate the drug consumption patterns in a population and accordingly the consequences with regard to adverse effects of cannabis from a public health perspective. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y.S. Wu

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 tomore » 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

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28 CFR 0.98 - Functions of Commissioner of Federal Prison Industries.

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2012-07-01

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28 CFR 0.98 - Functions of Commissioner of Federal Prison Industries.

Code of Federal Regulations, 2014 CFR

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... Prison Industries. 0.98 Section 0.98 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Bureau of Prisons § 0.98 Functions of Commissioner of Federal Prison Industries. The Director of the Bureau of Prisons is authorized as ex officio Commissioner of Federal Prison Industries and...

Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment.

PubMed

Englund, Amir; Morrison, Paul D; Nottage, Judith; Hague, Dominic; Kane, Fergus; Bonaccorso, Stefania; Stone, James M; Reichenberg, Avi; Brenneisen, Rudolf; Holt, David; Feilding, Amanda; Walker, Lucy; Murray, Robin M; Kapur, Shitij

2013-01-01

Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.

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

PubMed

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.

45 CFR 1321.31 - Appeal to Commissioner.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.31 Appeal to Commissioner. This...

45 CFR 1321.31 - Appeal to Commissioner.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.31 Appeal to Commissioner. This...

45 CFR 1321.31 - Appeal to Commissioner.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.31 Appeal to Commissioner. This...

45 CFR 1321.31 - Appeal to Commissioner.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.31 Appeal to Commissioner. This...

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

PubMed

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.

PubMed

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.

On the pharmacological properties of Delta9-tetrahydrocannabinol (THC).

PubMed

Costa, Barbara

2007-08-01

Cannabis is one of the first plants used as medicine, and the notion that it has potentially valuable therapeutic properties is a matter of current debate. The isolation of its main constituent, Delta9-tetrahydrocannabinol (THC), and the discovery of the endocannabinoid system (cannabinoid receptors CB1 and CB2 and their endogenous ligands) made possible studies concerning the pharmacological activity of cannabinoids. This paper reviews some of the most-important findings in the field of THC pharmacology. Clinical trials, anecdotal reports, and experiments employing animal models strongly support the idea that THC and its derivatives exhibit a wide variety of therapeutic applications. However, the psychotropic effects observed in laboratory animals and the adverse reactions reported during human trials, as well as the risk of tolerance development and potential dependence, limit the application of THC in therapy. Nowadays, researchers focus on other therapeutic strategies by which the endocannabinoid system might be modulated to clinical advantage (inhibitor or activator of endocannabinoid biosynthesis, cellular uptake, or metabolism). However, emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis-based medicines as new perspective to revisit the pharmacology of this plant.

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

PubMed

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.

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

PubMed Central

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

2013-01-01

BACKGROUND 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. METHODS 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 Δ9-tetrahydrocannabinol (THC)/per day followed by a 5-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. RESULTS 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 1.4–5.5 (0.04–245.6) at 0.25 h to 0.12–0.17 (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. CONCLUSIONS 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. PMID:23831756

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

PubMed

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.

Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats.

PubMed

Javadi-Paydar, Mehrak; Nguyen, Jacques D; Kerr, Tony M; Grant, Yanabel; Vandewater, Sophia A; Cole, Maury; Taffe, Michael A

2018-06-16

Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation. To compare thermoregulatory and locomotor responses to inhaled ∆ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination using an e-cigarette-based model in male and female rats METHODS: Male and female Wistar rats were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. Animals were then exposed to THC or CBD vapor using a propylene glycol (PG) vehicle. THC dose was adjusted via the concentration in the vehicle (12.5-200 mg/mL) and the CBD (100, 400 mg/mL) dose was also adjusted by varying the inhalation duration (10-40 min). Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation. Plasma samples obtained following inhalation in different groups of rats were compared for THC content. THC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity, and tail-withdrawal responses to THC did not differ between estrus and diestrus. CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. Co-administration of THC with CBD, in a 1:4 ratio, significantly decreased temperature and activity in an approximately additive manner and to similar extent in each sex. Plasma THC varied with the concentration in the PG vehicle but did not differ across rat sex. In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.

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

PubMed Central

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

2012-01-01

OBJECTIVES We characterize cannabinoid disposition in oral fluid (OF) after Dronabinol, synthetic oral Δ9-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. METHODS 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 10.5h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). RESULTS 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 0.25–1h. 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 4.5h post Sativex were ≤1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. CONCLUSIONS 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. PMID:23146820

Work place drug testing of police officers after THC exposure during large volume cannabis seizures.

PubMed

Doran, Gregory S; Deans, Ralph; De Filippis, Carlo; Kostakis, Chris; Howitt, Julia A

2017-06-01

Police officers responsible for the seizure and removal of illegally grown cannabis plants from indoor and outdoor growing operations face the prospect of THC exposure while performing their work duties. As a result, a study investigating the amount of THC on hands and uniforms of officers during raids on cannabis growing houses (CGHs) and forest cannabis plantations (FCPs) and in the air at these sites was conducted. Swabs of gloves/hands, chests, and heads/necks were collected and analysed for THC. Results of hand swabs indicated that officers removing plants from FCPs were exposed to THC concentrations up to 20 times those involved in raids at CGHs, which was mainly associated with the number and size of plants seized. Air samples collected inside cannabis houses showed no detectable THC. Air samples collected inside the cargo area of the storage trucks used during FCP raids indicated that THC can be volatilised when lush plants are compressed by other seized plants loaded on top of them in the truck over a period of several days, allowing composting of plants at the bottom of the load to commence. The elevated temperature and humidity inside the truck may assist the decarboxylation of THCA to THC, as well as increasing the rate of volatilisation of THC. More than 100 urine samples were collected from officers in raids on both CGHs and FCPs and all tested negative for THC. Removal of cannabis plants by officers often resulted in cuts, abrasions and ruptured blisters on exposed skin surfaces, particularly at FCPs. The results in this study suggest that even when small areas of damaged skin are directly exposed to THC by contact transfer, the likelihood of showing a positive THC urine test is low. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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

PubMed

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.

Prior exposure to THC increases the addictive effects of nicotine in rats.

PubMed

Panlilio, Leigh V; Zanettini, Claudio; Barnes, Chanel; Solinas, Marcelo; Goldberg, Steven R

2013-06-01

Although it is more common for drug abuse to progress from tobacco to cannabis, in many cases cannabis use develops before tobacco use. Epidemiological evidence indicates that prior cannabis use increases the likelihood of becoming dependent on tobacco. To determine whether this effect might be due to cannabis exposure per se, in addition to any genetic, social, or environmental factors that might contribute, we extended our series of studies on 'gateway drug' effects in animal models of drug abuse. Rats were exposed to THC, the main psychoactive constituent of cannabis, for 3 days (two intraperitoneal injections/day). Then, starting 1 week later, they were allowed to self-administer nicotine intravenously. THC exposure increased the likelihood of acquiring the nicotine self-administration response from 65% in vehicle-exposed rats to 94% in THC-exposed rats. When the price of nicotine was manipulated by increasing the response requirement, THC-exposed rats maintained higher levels of intake than vehicle-exposed rats, indicating that THC exposure increased the value of nicotine reward. These results contrast sharply with our earlier findings that prior THC exposure did not increase the likelihood of rats acquiring either heroin or cocaine self-administration, nor did it increase the reward value of these drugs. The findings obtained here suggest that a history of cannabis exposure might have lasting effects that increase the risk of becoming addicted to nicotine.

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

PubMed

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.

A novel single-step GC-MS/MS method for cannabinoids and 11-OH-THC metabolite analysis in hair.

PubMed

Angeli, Ilaria; Casati, Sara; Ravelli, Alessandro; Minoli, Mauro; Orioli, Marica

2018-06-05

THC, CBD, CBN, THC-COOH and 11-OH-THC are the most popular markers of cannabis consumption and abuse. The use of this drug is a serious social problem worldwide. In this study, a method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) operated in electron ionization (EI) with simple and rapid liquid-liquid extraction (LLE) and derivatization was developed and validated for the simultaneous determination of THC, CBD, CBN and 11-OH-THC in hair samples. The detection of all compounds was based on multiple reaction monitoring (MRM) transitions. The most important advantage of this method is the single-step, quick, easy and effective sample extraction procedure for THC, CBD, CBN and 11-OH-THC. The method showed a good linearity with a correlation coefficient (r 2 ) between 0.997 and 0.999 for all substances. The variation coefficient (%CV) was <5% for THC, 11-OH-THC and CBD and <13% for CBN. The limit of detection (LOD) was 0.03 pg/mg for 11-OH-THC and it ranged from 0.3 to 1.4 pg/mg for THC, CBD and CBN. The limit of quantification was 0.1 pg/mg for 11-OH-THC and it ranged from 0.9 to 4.7 pg/mg for THC, CBD and CBN. Analytical recovery was higher than 88% for 11-OH-THC and it ranged between 68 and 97% for THC, CBD and CBN. Intra- and inter-assay precision and accuracy were always lower than 9-14% and 5-9%, respectively. In parallel, we have quantified the THC-COOH level, following the methods previously set-up by us. The whole procedure was successfully applied to more than 200 different hair samples from cannabis consumers, disclosing the presence of 11-OH-THC in a range between 0.2 pg/mg and 27 pg/mg, and the presence of THC-COOH in a range between 0.05 pg/mg and 42.05 pg/mg. These data provided a good start towards the use of 11-THC-OH as alternative hair biomarker of cannabis consumption. Copyright © 2018 Elsevier B.V. All rights reserved.

26 CFR 36.3121(l)(4)-1 - Termination of agreement by Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

....3121(l)(4)-1 Section 36.3121(l)(4)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... OF FOREIGN SUBSIDIARIES § 36.3121(l)(4)-1 Termination of agreement by Commissioner. (a) Notice of....3121(l)(1)-1 is in effect may be terminated by the Commissioner, with the prior concurrence of the...

Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats.

PubMed

Fadda, Paola; Robinson, Lianne; Fratta, Walter; Pertwee, Roger G; Riedel, Gernot

2004-12-01

Cannabinoid receptors in the brain (CB(1)) take part in modulation of learning, and are particularly important for working and short-term memory. Here, we employed a delayed-matching-to-place (DMTP) task in the open-field water maze and examined the effects of cannabis plant extracts rich in either Delta(9)-tetrahydrocannabinol (Delta(9)-THC), or rich in cannabidiol (CBD), on spatial working and short-term memory formation in rats. Delta(9)-THC-rich extracts impaired performance in the memory trial (trial 2) of the DMTP task in a dose-dependent but delay-independent manner. Deficits appeared at doses of 2 or 5 mg/kg (i.p.) at both 30 s and 4 h delays and were similar in severity compared with synthetic Delta(9)-THC. Despite considerable amounts of Delta(9)-THC present, CBD-rich extracts had no effect on spatial working/short-term memory, even at doses of up to 50 mg/kg. When given concomitantly, CBD-rich extracts did not reverse memory deficits of the additional Delta(9)-THC-rich extract. CBD-rich extracts also did not alter Delta(9)-THC-rich extract-induced catalepsy as revealed by the bar test. It appears that spatial working/short-term memory is not sensitive to CBD-rich extracts and that potentiation and antagonism of Delta(9)-THC-induced spatial memory deficits is dependent on the ratio between CBD and Delta(9)-THC.

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

PubMed

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.

Assessing New York's Commissioner of Education

ERIC Educational Resources Information Center

Meyer, Peter

2011-01-01

In this article, the author talks about the resignation of New York State's commissioner of education David Steiner, and how it will affect the state's Race to the Top. He contends that Steiner was savvy enough to understand the importance of Race to the Top and able enough to turn the state's education energies toward it. The "Washington…

Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).

PubMed

Kasten, Chelsea R; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L

2018-05-01

Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.

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

PubMed

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.

PubMed

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.

21 CFR 71.27 - Listing and exemption from certification on the Commissioner's initiative.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Listing and exemption from certification on the Commissioner's initiative. 71.27 Section 71.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Listing and exemption from certification on the Commissioner's initiative. Where a petition for a...

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

PubMed

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.

Acute effects of THC on time perception in frequent and infrequent cannabis users.

PubMed

Sewell, R Andrew; Schnakenberg, Ashley; Elander, Jacqueline; Radhakrishnan, Rajiv; Williams, Ashley; Skosnik, Patrick D; Pittman, Brian; Ranganathan, Mohini; D'Souza, D Cyril

2013-03-01

Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects' cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ⁹-tetrahydrocannabinol (THC), leading to variable pharmacokinetics, and some used whole-plant cannabis containing cannabinoids other than THC. Our study attempted to address these limitations. This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception. THC was hypothesized to produce transient, dose-related time overestimation and underproduction. Frequent cannabis smokers were hypothesized to show blunted responses to these alterations. IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind, randomized, counterbalanced, crossover, placebo-controlled studies. Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day. All doses induced time overestimation and underproduction. Chronic cannabis use had no effect on baseline time perception. While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses, frequent cannabis users showed no differences. THC effects on time perception were not dose related. A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction. This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception.

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.

PubMed

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.

PubMed

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.

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

PubMed Central

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

2015-01-01

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 (Δ9-THC) on the auditory steady-state response (ASSR) were studied in humans (n=20) who completed 3 test days during which they received intravenous Δ9-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). Δ9-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 Δ9-THC. Δ9-THC (0.03 mg/kg) reduced evoked power during 40 Hz stimulation at a trend level. Recent users of cannabis showed blunted Δ9-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. PMID:25709097

45 CFR 1321.31 - Appeal to Commissioner.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Appeal to Commissioner. 1321.31 Section 1321.31 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE...

26 CFR 1.148-10A - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Anti-abuse rules and authority of Commissioner... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable to Certain Bonds Sold Prior to July 8, 1997 § 1.148-10A Anti-abuse rules and authority of Commissioner. (a) through (b)(1...

26 CFR 1.148-10A - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Anti-abuse rules and authority of Commissioner... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable to Certain Bonds Sold Prior to July 8, 1997 § 1.148-10A Anti-abuse rules and authority of Commissioner. (a) through (b)(1...

26 CFR 1.148-10A - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Anti-abuse rules and authority of Commissioner... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable to Certain Bonds Sold Prior to July 8, 1997 § 1.148-10A Anti-abuse rules and authority of Commissioner. (a) through (b)(1...

26 CFR 1.148-10A - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Anti-abuse rules and authority of Commissioner... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable to Certain Bonds Sold Prior to July 8, 1997 § 1.148-10A Anti-abuse rules and authority of Commissioner. (a) through (b)(1...

26 CFR 1.148-10A - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Anti-abuse rules and authority of Commissioner... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Regulations Applicable to Certain Bonds Sold Prior to July 8, 1997 § 1.148-10A Anti-abuse rules and authority of Commissioner. (a) through (b)(1...

The psychoactive substance of cannabis Δ9-tetrahydrocannabinol (THC) negatively regulates CFTR in airway cells.

PubMed

Chang, Sheng-Wei; Wellmerling, Jack; Zhang, Xiaoli; Rayner, Rachael E; Osman, Wissam; Mertz, Sara; Amer, Amal O; Peeples, Mark E; Boyaka, Prosper N; Cormet-Boyaka, Estelle

2018-06-18

Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function. Cultures of human bronchial epithelial cell line 16HBE14o- and primary human airway epithelial cells were exposed to THC. The expression of CFTR protein was determined by immunoblotting and CFTR function was measured using Ussing chambers. We also used specific pharmacological inhibitors of EGFR and ERK to determine the role of this pathway in THC-induced regulation of CFTR. THC decreased CFTR protein expression in primary human bronchial epithelial cells. This decrease was associated with reduced CFTR-mediated short-circuit currents. THC also induced activation of the ERK MAPK pathway via activation of EGFR. Inhibition of EGFR or MEK/ERK prevented THC-induced down regulation of CFTR protein expression. THC negatively regulates CFTR and this is mediated through the EGFR/ERK axis. This study provides the first evidence that THC present in marijuana reduces the expression and function of CFTR in airway epithelial cells. Copyright © 2018. Published by Elsevier B.V.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

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

2013-01-01

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 Δ9-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. PMID:21637933

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

PubMed

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'.

Radioimmunoanalysis of delta-9-THC in blood by means of an /sup 125/I tracer. [Delta-9-Tetrahydrocannabinol

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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, /sup 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.more » Methanol dilution gave better results than direct analysis. The /sup 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.« less

Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users.

PubMed

Curran, H Valerie; Brignell, Catherine; Fletcher, Sally; Middleton, Paul; Henry, John

2002-10-01

Although some aspects of memory functions are known to be acutely impaired by delta(9)-tetrahydrocannabinol (delta(9)-THC; the main active constituent of marijuana), effects on other aspects of memory are not known and the time course of functional impairments is unclear. The present study aimed to detail the acute and residual cognitive effects of delta(9)-THC in infrequent cannabis users. A balanced, double-blind cross-over design was used to compare the effects of 7.5 mg and 15 mg delta(9)-THC with matched placebo in 15 male volunteers. Participants were assessed pre and 1, 2, 4, 6, 8, 24 and 48 h post-drug. Delta(9)-THC 15 mg impaired performance on two explicit memory tasks at the time of peak plasma concentration (2 h post-drug). At the same time point, performance on an implicit memory task was preserved intact. The higher dose of delta(9)-THC resulted in no learning whatsoever occurring over a three-trial selective reminding task at 2 h. Working memory was generally unaffected by delta(9)-THC. In several tasks, delta(9)-THC increased both speed and error rates, reflecting "riskier" speed-accuracy trade-offs. Subjective effects were also most marked at 2 h but often persisted longer, with participants rating themselves as "stoned" for 8 h. Participants experienced a strong drug effect, liked this effect and, until 4 h, wanted more oral delta(9)-THC. No effects of delta(9)-THC were found 24 or 48 h following ingestion indicating that the residual effects of oral delta(9)-THC are minimal. These data demonstrate that oral delta(9)-THC impairs episodic memory and learning in a dose-dependent manner whilst sparing perceptual priming and working memory.

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

PubMed Central

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

Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

PubMed Central

Gunasekaran, N; Long, LE; Dawson, BL; Hansen, GH; Richardson, DP; Li, KM; Arnold, JC; McGregor, IS

2009-01-01

Background and purpose: Δ9-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. Experimental approach: 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. Key results: 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-Δ9-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. Conclusions and implications: 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’. PMID:19681888

77 FR 59196 - Office of the Commissioner of Food and Drugs; Delegation of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0012] Office of the Commissioner of Food and Drugs; Delegation of Authority AGENCY: Food and Drug Administration, HHS. ACTION: Notice. Notice is hereby given that I have delegated to the Commissioner of Food and...

75 FR 43963 - Notice of Commissioner and Staff Attendance at National Association of Regulatory Utility...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at National Association of Regulatory Utility Commissioners Summer Committee Meetings July 20.../or Commission staff may attend the following meeting: Committee on Electricity: Sacramento Convention...

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

PubMed

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).

76 FR 71006 - Notice of Commissioner and Staff Attendance at National Association of Regulatory Utility...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at National Association of Regulatory Utility Commissioners 123rd Annual Meeting The Federal.../or Commission staff may attend the following meeting: FERC/National Association of Regulatory Utility...

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

PubMed Central

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.

PubMed

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.

PubMed

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).

Soft tissue effects of the THC:YAG laser on canine vocal cords.

PubMed

Kay, S L; Oz, M C; Haber, M; Blitzer, A; Treat, M R; Trokel, S L

1992-09-01

Recently, a laser based on a thulium-holmium-chromium (THC) doped Yttrium-aluminum-garnet (YAG) rod has been developed that produces light of 2.15 microns wavelength and can be transmitted through a low OH- silica fiberoptic cable. This wavelength falls on one of the peaks of the energy absorption spectrum of water. Thus, the THC:YAG laser eliminates the disadvantage of a cumbersome delivery system found in the CO2 laser while still providing precise cutting and minimal tissue injury inherent in lasers emitting light absorbed by water. We evaluated the soft tissue effects of this laser on canine vocal cords. Ablative lesions were produced by the THC:YAG laser and histologically examined on postoperative days 1, 7, and 28. Results indicate that the depth of tissue penetration is easily controlled and the healing response to tissue injury is comparable to that of the CO2 laser. The THC:YAG laser should prove to be a superior laser for use in otorhinolaryngology, especially when adapted to a flexible endoscope.

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

PubMed

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.

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

PubMed

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

2013-05-01

A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (Cmax) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (Tmax) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.

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

PubMed Central

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

46 CFR 502.243 - Participation of absent Commissioner.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND PROCEDURE Oral Argument; Submission for Final Decision § 502.243 Participation of absent... participate in a decision shall participate in making that decision after reading the transcript of oral... 46 Shipping 9 2010-10-01 2010-10-01 false Participation of absent Commissioner. 502.243 Section...

THC:CBD in Daily Practice: Available Data from UK, Germany and Spain.

PubMed

Fernández, Óscar

2016-01-01

From the time Sativex (THC:CBD) oromucosal spray first became available in European Union countries in 2010 for the management of treatment-resistant multiple sclerosis (MS) spasticity, data from daily practice have been collected through various projects. A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported. The most recent analysis of a retrospective registry established in the United Kingdom (UK), Germany and Switzerland, which collected safety data on more than 900 patients, has indicated a positive risk-benefit profile for THC:CBD oromucosal spray during long-term use. Long-term continuation rates were 68% (mean follow-up time 1 year) and the mean dose was 5.4 sprays/day. No new safety concerns were identified, and adverse events of special interest for a cannabis-based medicine were limited. The UK registry has since been closed but remains open in Germany and Switzerland. A prospective safety study undertaken in Spain involved 207 patients from 13 specialized MS centres who had been prescribed THC:CBD oromucosal spray. The findings aligned closely with the UK/German/Swiss registry data in terms of 1-year continuation rates (64.7%), mean daily dose (6.6 sprays/day) and safety profile, including no evidence of addiction, abuse or misuse. The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice. © 2016 S. Karger AG, Basel.

THC:CBD spray and MS spasticity symptoms: data from latest studies.

PubMed

Rekand, Tiina

2014-01-01

New clinical experience with 9-delta-tetrahydocannabinol (THC) and cannabidiol (CBD) oromucosal spray (Sativex®) involving more than an additional 1,000 patients with MS spasticity (approximately 150 in clinical studies and 900 in post-marketing surveillance studies) have become available in 2013 and are reviewed. A randomized, placebo controlled long-term follow-up clinical trial with THC:CBD spray versus placebo demonstrated that it was not associated with cognitive decline, depression or significant mood changes after 12 months of treatment. Furthermore, in a prospective observational pilot study involving 33 patients (60% female) aged 33-68 years and a mean disease duration of 6.6 years, THC:CBD oromucosal spray did not adversely influence standard driving ability in patients with moderate to severe MS spasticity. Other new long term observational data about the use of THC:CBD oromucosal spray in clinical practice are available from patient registries in the UK, Germany and Spain. Findings to date reinforce the efficacy and safety observed in Phase III clinical trials. It is of interest that in practice average dosages used by patients tended to be lower than those reported in clinical studies (5-6.4 vs. >8 sprays/day), and effectiveness was maintained in the majority of patients. Importantly, no additional safety concerns were identified in the registry studies which included findings from patients who have been treated for prolonged periods (in the German/UK registry 45% of patients had >2 years exposure). Thus, these new data support a positive benefit-risk relationship for THC:CBD oromucosal spray during longer-term use. © 2014 S. Karger AG, Basel.

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

PubMed

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.

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

P. Dixon

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 themore » 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

Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant.

PubMed

Justinova, Zuzana; Munzar, Patrik; Panlilio, Leigh V; Yasar, Sevil; Redhi, Godfrey H; Tanda, Gianluigi; Goldberg, Steven R

2008-11-01

Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence.

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

PubMed

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.

PubMed

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

Combined effects of THC and caffeine on working memory in rats

PubMed Central

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

77 FR 44609 - Notice of Commissioner and Staff Attendance at the National Association of Regulatory Utility...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at the National Association of Regulatory Utility Commissioners 2012 Summer Committee Meetings The... Commission and/or Commission staff may attend the following meetings: Gas and Electricity Interdependencies...

Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of Δ9-THC in cannabis users

PubMed Central

Lile, Joshua A.; Kelly, Thomas H.; Charnigo, Richard J.; Stinchcomb, Audra L.; Hays, Lon R.

2013-01-01

Oral Δ9-tetrahydrocannabinol (Δ9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral Δ9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral Δ9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. Δ9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug- sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral Δ9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral Δ9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response. PMID:23754596

THC inhibits the expression of ethanol-induced locomotor sensitization in mice.

PubMed

Filev, Renato; Engelke, Douglas S; Da Silveira, Dartiu X; Mello, Luiz E; Santos-Junior, Jair G

2017-12-01

The motivational circuit activated by ethanol leads to behavioral changes that recruit the endocannabinoid system (ECS). Case reports and observational studies suggest that the use of Cannabis sp. mitigates problematic ethanol consumption in humans. Here, we verified the effects of the two main phytocannabinoid compounds of Cannabis sp., cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), in the expression of ethanol-induced locomotor sensitization in mice. Male adult DBA/2 mice were exposed to locomotor sensitization by daily intraperitoneal injections of ethanol (2.5 g/kg) for 12 days; control groups received saline. After the acquisition phase, animals were treated with cannabinoids: CBD (2.5 mg/kg); THC (2.5 mg/kg); CBD + THC (1:1 ratio), or vehicle for 4 days with no access to ethanol during this period. One day after the last cannabinoid injection, all animals were challenged with ethanol (2.0 g/kg) to evaluate the expression of the locomotor sensitization. Mice treated with THC alone or THC + CBD showed reduced expression of locomotor sensitization, compared to the vehicle control group. No effects were observed with CBD treatment alone. Our findings showing that phytocannabinoid treatment prevents the expression of behavioral sensitization in mice provide insight into the potential therapeutic use of phytocannabinoids in alcohol-related problems. Copyright © 2017 Elsevier Inc. All rights reserved.

78 FR 43877 - Notice of Commissioner and Staff Attendance at the National Association of Regulatory Utility...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-22

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at the National Association of Regulatory Utility Commissioners 2013 Summer Committee Meetings The... Downtown Hotel, 1550 Court Place, Denver, CO 80202. Further information may be found at http://summer...

Effect of Norbinaltorphimine on Δ9-Tetrahydrocannabinol (THC)-Induced Taste Avoidance in Adolescent and Adult Sprague-Dawley Rats

PubMed Central

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

2017-01-01

Rationale The aversive effects of Δ9-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. Objectives 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. Methods 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. Results 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. Conclusions 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. PMID:26025420

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

PubMed

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.

Social Archaeological Approaches in Port and Harbour Studies

NASA Astrophysics Data System (ADS)

Rogers, Adam

2013-12-01

This introductory article to the special issue of the Journal of Maritime Archaeology offers a comparative perspective on the theme of archaeological theory and social archaeological approaches to ports and harbours. As a specialist in Roman archaeology I was keen to explore the way in which specialists in other areas of archaeology approached the archaeology of ports and harbours and whether different approaches and perspectives may be able to add nuances to the way in which material is interpreted. The volume brings together a collection of exciting new studies which explore social themes in port and harbour studies with the intention to encourage debate and the use of new interpretative perspectives. This article examines a number of interpretative themes including those relating to architectural analyse, human behaviour, action and experience and artefact analysis. These themes help us to move towards a more theoretically informed ports and harbour archaeology which focuses on meaning as well as description. The emphasis on theory within archaeology allows us to be more ambitious in our interpretative frameworks including in Roman archaeology which has not tended to embrace the theoretical aspects of the archaeological discipline with as much enthusiasm as some other areas of archaeology.

Precocious hearing in harbour porpoise neonates.

PubMed

Wahlberg, Magnus; Delgado-García, Lara; Kristensen, Jakob H

2017-02-01

Hearing is the primary sensory modality for toothed whales, but it is not known at which age it is fully developed. For newborn calves, hearing could fill an important function in maintaining contact with the mother and to develop echolocation skills. We non-invasively measured the auditory brainstem response (ABR) in two neonate (age 1-4 days) and three adult harbour porpoises (Phocoena phocoena). The stimuli consisted of clicks centred at 130 kHz, which is within the frequency band used for echolocation and communication in this species. The temporal pattern of the neonate ABRs was indistinguishable to the adult ones. There were no significant differences between calves and adults regarding hearing thresholds and ABR latencies. The ABR amplitudes were up to more than an order of magnitude larger in newborns than in adults, most likely due to the neonates' smaller size. These results indicate that hearing is fully developed within a day after birth, which suggests that harbour porpoise neonates have the earliest hearing development of any mammal studied so far. This may be explained by the evolutionary pressures imposed by the aquatic environment for a rapid development of the key sensory system in harbour porpoises.

A Management Review of the Institutions of Higher Learning: Commissioner's Office, University Foundations and Athletic Programs.

ERIC Educational Resources Information Center

Mississippi State Legislature, Jackson. Performance Evaluation and Expenditure Review Committee.

A state mandated evaluation study was done of certain programs and activities of the Mississippi Commissioner's Office of the Institutions of Higher Learning (IHL) including the Commissioner's Fund and operations of university foundations and athletic programs. This report presents findings, recommendations, and documentation, as well as responses…

24 CFR 27.10 - Designation of a foreclosure commissioner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and Urban Development NONJUDICIAL FORECLOSURE OF MULTIFAMILY AND SINGLE FAMILY MORTGAGES Nonjudicial Foreclosure of Multifamily Mortgages § 27.10 Designation of a foreclosure commissioner. (a) When the Secretary determines that a multifamily mortgage should be foreclosed under the Act and this subpart, the General...

24 CFR 27.10 - Designation of a foreclosure commissioner.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Urban Development NONJUDICIAL FORECLOSURE OF MULTIFAMILY AND SINGLE FAMILY MORTGAGES Nonjudicial Foreclosure of Multifamily Mortgages § 27.10 Designation of a foreclosure commissioner. (a) When the Secretary determines that a multifamily mortgage should be foreclosed under the Act and this subpart, the General...

24 CFR 27.10 - Designation of a foreclosure commissioner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Urban Development NONJUDICIAL FORECLOSURE OF MULTIFAMILY AND SINGLE FAMILY MORTGAGES Nonjudicial Foreclosure of Multifamily Mortgages § 27.10 Designation of a foreclosure commissioner. (a) When the Secretary determines that a multifamily mortgage should be foreclosed under the Act and this subpart, the General...

24 CFR 27.10 - Designation of a foreclosure commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Urban Development NONJUDICIAL FORECLOSURE OF MULTIFAMILY AND SINGLE FAMILY MORTGAGES Nonjudicial Foreclosure of Multifamily Mortgages § 27.10 Designation of a foreclosure commissioner. (a) When the Secretary determines that a multifamily mortgage should be foreclosed under the Act and this subpart, the General...

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

PubMed

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

The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity.

PubMed

Celius, Elisabeth G; Vila, Carlos

2018-05-01

Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it. In this article, we review the evidence relating the antispasticity medicine, Δ 9 -tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex ® ), and its potential impact on driving performance. Articles were identified by searching PubMed from 1/1/2000 to 30/6/2017 using a specified list of search terms. The articles identified using these search terms were augmented with relevant references from these papers and other articles known to the authors. The results from THC:CBD oromucosal spray driving studies and real-world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray. The majority of patients reported an improvement in driving ability after starting THC:CBD oromucosal spray, and it was speculated that this may be related to reduced spasticity and/or better cognitive function. It should be noted that THC blood levels are significantly lower than the levels associated with recreational use of herbal cannabis. THC:CBD oromucosal spray was shown not to impair driving performance. However, periodic assessment of patients with MS driving ability is recommended, especially after relapses and changes in treatment. Blood THC measurements might be above authorized thresholds for some countries following administration of THC:CBD oromucosal spray, thus specific knowledge of each country's driving regulations and a medical certificate are recommended.

19 CFR 115.17 - Appeal to Commissioner of Customs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Appeal to Commissioner of Customs. 115.17 Section 115.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.17 - Appeal to Commissioner of Customs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Appeal to Commissioner of Customs. 115.17 Section 115.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.17 - Appeal to Commissioner of Customs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Appeal to Commissioner of Customs. 115.17 Section 115.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.17 - Appeal to Commissioner of Customs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Appeal to Commissioner of Customs. 115.17 Section 115.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.17 - Appeal to Commissioner of Customs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Appeal to Commissioner of Customs. 115.17 Section 115.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

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

PubMed

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.

PubMed

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.

PubMed

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.

PubMed

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.

Therapeutic issues of marijuana and THC (tetrahydrocannabinol).

PubMed

Ungerleider, J T; Andrysiak, T

1985-05-01

This article summarizes current knowledge about the medicinal value of cannabis and its principal psychoactive ingredient, delta 9-tetrahydrocannabinol (THC), particularly in the control of nausea and vomiting, in glaucoma, and in reduction of spasticity in multiple sclerosis. The major issues in the controversy about marijuana and medicine, primarily moral and ethical, are discussed.

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

E. Gonnenthal; N. Spyoher

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) THCmore » 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, sensitivity and validation studies

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

E. Sonnenthale

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&O) 2000 [1534471]) and ''Technical Work Plan for Nearfield Environment Thermal Analyses and Testing'' (CRWMS M&O 2000 [153309]). These models include the Drift Scale Test (DST) THC Model and several THCmore » 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

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

PubMed

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.

Thermal-hydrodynamic-chemical (THC) modeling based on geothermal field data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiryukhin, Alexey; Xu, Tianfu; Pruess, Karsten

Data on fluid chemistry and rock mineralogy are evaluated for a number of geothermal fields located in the volcanic arc of Japan and Kamchatka, Russia, Common chemical characteristics are identified and used to define scenarios for detailed numerical modeling of coupled thermal hydrodynamic chemical (THC) processes. The following scenarios of parental geothermal fluid upflow were studied: (1) single-phase conditions, 260 C at the bottom ( Ogiri type); (2) two-phase conditions, 300 C at the bottom ( Hatchobaru type); and (3) heat pipe conditions, 260 C at the bottom ( Matsukawa type). THC modeling for the single-phase upflow scenario shows wairakite,more » quartz, K-feld spar and chlorite formed as the principal secondary minerals in the production zone, and illite-smectite formed below 230 C. THC modeling of the two-phase upflow shows that quartz, K-feldspar (microcline), wairakite and calcite precipitate in the model as principal secondary minerals in the production zone. THC modeling of heat pipe conditions shows no significant secondary deposition of minerals (quartz, K-feldspar, zeolites) in the production zone. The influence of thermodynamic and kinetic parameters of chemical interaction, and of mass fluxes on mineral phase changes, was found to be significant, depending on the upflow regime. It was found that no parental geothermal fluid inflow is needed for zeolite precipitation, which occurs above 140 C in saturated andesite, provided that the porosity is greater than 0.001. In contrast, quartz and K-feldspar precipitation may result in a significant porosity reduction over a hundred-year time scale under mass flux conditions, and complete fracture sealing will occur given sufficient time under either single-phase or two-phase upflow scenarios. A heat pipe scenario shows no significant porosity reduction due to lack of secondary mineral phase deposition.« less

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

PubMed Central

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

Outcrop Geomorphology and Sediment Characterization in Killary Harbour, Ireland

NASA Astrophysics Data System (ADS)

Crouse, L. E.; Sautter, L.

2016-02-01

Killary Harbour in western Ireland is one of three fjards found in the country. A fjard is formed by glacial carving, but differs from fjords in being shallower, shorter, and broader in profile. The Harbour is located near the border of County Mayo and County Galway. The Marine Institute of Ireland, The Geological Survey of Ireland, and the INFOMAR project, led by chief scientist Kevin Sheehan, conducted bathymetric surveys in Killary Harbour, Ireland during July and August of 2014 aboard the R/V Celtic Voyager. A Kongsberg EM2040 multi-beam sonar was utilized to acquire the raw data, which was post-processed using CARIS HIPS and SIPS 9.0. The area of study is shallow harbor seafloor depths ranging from 15 to 60 m. An abundance of rocky outcrops and narrow channels are present in the North-Western section of the study area. Backscatter data collected during acquisition were used to determine the relative hardness of seafloor sediments and rocky outcrops. Characterization of the bathymetric terrain and sediments of the harbour could prove to be useful in finding hardbottom substrate for ideal fish habitat.

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

PubMed

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

Do marginal investments made by NHS healthcare commissioners in the UK produce the outcomes they hope to achieve? Observational study

PubMed Central

O'Cathain, Alicia; Sampson, Fiona; Strong, Mark; Pickin, Mark; Goyder, Elizabeth; Dixon, Simon

2015-01-01

Objective To investigate the effect of targeted marginal annual investments by local healthcare commissioners on the outcomes they expected to achieve with these investments. Design Controlled before and after study. Setting: 152 commissioning organisations (primary care trusts) in England. Methods National surveys of commissioning managers in 2009 and 2010 to identify: the largest marginal investments made in four key conditions/services (diabetes, coronary heart disease, chronic pulmonary airways disease and emergency and urgent care) in 2008/2009 and 2009/2010; the outcomes commissioners expected to achieve with these investments; and the processes commissioners used to develop these investments. Collation of routinely available data on outcomes commissioners expected from these investments over the period 2007/2008 to 2010/2011. Results 51% (77/152) of commissioners agreed to participate in the survey in 2009 and 60% (91/152) in 2010. Around half reported targeted marginal investments in each condition/service each year. Routine data on many of the outcomes they expected to achieve through these investments were not available. Also, commissioners expected some outcomes to be achieved beyond the time scale of our study. Therefore, only a limited number of outcomes of investments were tested. Outcomes included directly standardised emergency admission rates for the four conditions/services, and the percentage of patients with diabetes with glycated haemoglobin <7. There was no evidence that targeted marginal investments reduced emergency admission rates. There was evidence of an improvement in blood glucose management for diabetes for commissioners investing to improve diabetes care but this was compromised by a change in how the outcome was measured in different years. This investment was unlikely to be cost-effective. Conclusions Commissioners made marginal investments in specific health conditions and services with the aim of improving a wide range of outcomes

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

PubMed

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, S.F.; Newport, G.D.; Scallet, A.C.

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 weremore » 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.« less

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

PubMed

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.

Cannabis with high δ9-THC contents affects perception and visual selective attention acutely: an event-related potential study.

PubMed

Böcker, K B E; Gerritsen, J; Hunault, C C; Kruidenier, M; Mensinga, Tj T; Kenemans, J L

2010-07-01

Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. Twenty-four participants smoked cannabis cigarettes with four doses of THC on four test days in a randomized, double blind, placebo-controlled, crossover study. Two hours after THC exposure the participants performed a visual selective attention task and concomitant ERPs were recorded. Accuracy decreased linearly and reaction times increased linearly with THC dose. However, performance measures and most of the ERP components related specifically to selective attention did not show significant dose effects. Only in relatively light cannabis users the Occipital Selection Negativity decreased linearly with dose. Furthermore, ERP components reflecting perceptual processing, as well as the P300 component, decreased in amplitude after THC exposure. Only the former effect showed a linear dose-response relation. The decrements in performance and ERP amplitudes induced by exposure to cannabis with high THC content resulted from a non-selective decrease in attentional or processing resources. Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America. Copyright 2010 Elsevier Inc. All rights reserved.

Phagocytosis in pup and adult harbour, grey and harp seals.

PubMed

Frouin, Héloïse; Lebeuf, Michel; Hammill, Mike; Fournier, Michel

2010-04-15

Knowledge on pinniped immunology is still in its infancy. For instance, age-related and developmental aspects of the immune system in pinnipeds need to be better described. The present study examined the phagocytic activity and efficiency of harbour, grey and harp seal leukocytes. In the first part of the study, peripheral blood was collected from captive female harbour seals of various ages. Data showed an age-related decrease in phagocytosis in female harbour seals from sub-adult to adulthood. In the second part of the study, changes in phagocytosis were quantified during lactation in wild newborn harbour, grey and harp seals and in their mothers (harp and grey seals). In newborns of the same age, leukocytes of harbour and harp seals phagocytosed less than those of grey seal pups. The phagocytic activity and efficiency increased significantly from early to mid-lactation in newborn harbour seals, and from early to late lactation in newborn grey seals, which could suggest that the transfer of phagocytosis-promoting factor(s) in colostrum is an important feature of temporary protection for pups. In contrast, no changes in phagocytic activity and efficiency were observed in lactating females of the two seal species, harp and grey, examined. At late lactation, phagocytic activity in both grey and harp seal pups and phagocytic efficiency in grey seal pups were significantly higher than in their mothers. These results could reflect either the capacity of phagocytes of the newborn harp and grey seals to respond to pathogens. Results from this study suggest that the phagocytosis of the seal species examined is not fully developed at birth as it generally increases in pups during lactation. Thereafter, the phagocytic activity of seals appears to decrease throughout adulthood. Copyright 2009 Elsevier B.V. All rights reserved.

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

PubMed

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.

PubMed

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.

PubMed

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.

A STUDY OF COUNTY COMMISSIONERS' PRECEPTION OF THE NORTH CAROLINA COOPERATIVE EXTENSION SERVICE, NORTHEASTERN EXTENSION DISTRICT, NORTH CAROLINA.

ERIC Educational Resources Information Center

WHITE, ESTELLE EDWARDS

AN INTERVIEW QUESTIONNAIRE WAS USED TO DISCOVER HOW 85 ELECTED COUNTY COMMISSIONERS IN THE NORTHEASTERN EXTENSION DISTRICT OF NORTH CAROLINA PERCEIVED THE COOPERATIVE EXTENSION SERVICE. THE EXTENT TO WHICH TENURE AS A COMMISSIONER, OCCUPATION, EDUCATION, AGE, AND INVOLVEMENT IN EXTENSION ACTIVITIES WERE ASSOCIATED WITH THE PERCEPTION OF…

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 13 2013-07-01 2012-07-01 true How do I determine the outlet THC... Control Efficiency/outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and... methods in this section to determine either the outlet THC emissions or add-on control device emission...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 13 2014-07-01 2014-07-01 false How do I determine the outlet THC... Control Efficiency/outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and... methods in this section to determine either the outlet THC emissions or add-on control device emission...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 12 2011-07-01 2009-07-01 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...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 13 2012-07-01 2012-07-01 false How do I determine the outlet THC... Control Efficiency/outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and... methods in this section to determine either the outlet THC emissions or add-on control device emission...

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

PubMed

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.

19 CFR 115.18 - Decision of Commissioner of Customs final.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Decision of Commissioner of Customs final. 115.18 Section 115.18 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.18 - Decision of Commissioner of Customs final.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Decision of Commissioner of Customs final. 115.18 Section 115.18 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.18 - Decision of Commissioner of Customs final.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Decision of Commissioner of Customs final. 115.18 Section 115.18 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.18 - Decision of Commissioner of Customs final.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Decision of Commissioner of Customs final. 115.18 Section 115.18 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

19 CFR 115.18 - Decision of Commissioner of Customs final.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Decision of Commissioner of Customs final. 115.18 Section 115.18 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarafian, Theodore; Montes, Cindy; Harui, Airi

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that {delta}{sup 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 epithelialmore » 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 < 0.05) and were 80- to 100-fold more sensitive to the inhibitory effects of THC. Studies using SR144528, a selective CB2R antagonist, verified that these effects were mediated by the CB2R. Marijuana smoke extract, but not smoke extracts from tobacco or placebo marijuana cigarettes, reproduced these effects (p < 0.05). THC decreased ATP level and mitochondrial membrane potential ({psi}{sub 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

Sources of contamination and modelled pollutant trajectories in a Mediterranean harbour (Tarragona, Spain).

PubMed

Mestres, M; Sierra, J P; Mösso, C; Sánchez-Arcilla, A

2010-06-01

The proximity of commercial harbours to residential areas and the growing environmental awareness of society have led most port authorities to include environmental management within their administration plan. Regarding water quality, it is necessary to have the capacity and tools to deal with contamination episodes that may damage marine ecosystems and human health, but also affect the normal functioning of harbours. This paper presents a description of the main pollutant sources in Tarragona Harbour (Spain), and a numerical analysis of several pollution episodes based on the Port Authority's actual environmental concerns. The results show that pollution generated inside the harbour tends to remain confined within the port, whereas it is very likely that oil spills from a nearby monobuoy may affect the neighbouring beaches. The present combination of numerical models proves itself a useful tool to assess the environmental risk associated to harbour activities and potential pollution spills.

Comparative effects of phencyclidine (PCP) and. delta. /sup 9/-tetrahydrocannabinol (THC) on glucose oxidation in the rat testis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Husain, S.; Bauer, V.

Glucose and fructose are important fuels of cellular energetics in organs like testis and brain. The previous in-vitro studies indicated that THC may disrupt many gonadal functions by inhibiting energy metabolism in the testis. PCP is sold on the street as any one of a variety of psychoactive drugs. Most commonly it is misrepresented as THC. Therefore, to compare the effects of PCP and THC on glucose utilization, in-vitro radiorespirometric experiments were conducted in rat testicular tissues. The /sup 14/CO/sub 2/ production from 5.5 mM radiolabelled glucose was followed in the presence and absence of 0.2, 0.1, 0.05, 0.01, 0.005,more » 0.0025 mM PCP. PCP produced a dose-dependent biphasic effect, stimulating /sup 14/CO/sub 2/ production by 6.2, 17 and 5.8% and then inhibiting it by 13.2, 15.4 and 8.9% with respective concentrations of PCP. This is in contrast to THC which produced a dose-related inhibition of 15.2, 18.1, 20.1 and 25.3% in /sup 14/CO/sub 2/ production with 0.1, 0.2, 0.3 and 0.4 mM THC. These observations are significant due to the possible abuse of PCP together with THC either deliberately or by misrepresentation.« less

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

PubMed

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.

Do marginal investments made by NHS healthcare commissioners in the UK produce the outcomes they hope to achieve? Observational study.

PubMed

O'Cathain, Alicia; Sampson, Fiona; Strong, Mark; Pickin, Mark; Goyder, Elizabeth; Dixon, Simon

2015-11-06

To investigate the effect of targeted marginal annual investments by local healthcare commissioners on the outcomes they expected to achieve with these investments. Controlled before and after study. 152 commissioning organisations (primary care trusts) in England. National surveys of commissioning managers in 2009 and 2010 to identify: the largest marginal investments made in four key conditions/services (diabetes, coronary heart disease, chronic pulmonary airways disease and emergency and urgent care) in 2008/2009 and 2009/2010; the outcomes commissioners expected to achieve with these investments; and the processes commissioners used to develop these investments. Collation of routinely available data on outcomes commissioners expected from these investments over the period 2007/2008 to 2010/2011. 51% (77/152) of commissioners agreed to participate in the survey in 2009 and 60% (91/152) in 2010. Around half reported targeted marginal investments in each condition/service each year. Routine data on many of the outcomes they expected to achieve through these investments were not available. Also, commissioners expected some outcomes to be achieved beyond the time scale of our study. Therefore, only a limited number of outcomes of investments were tested. Outcomes included directly standardised emergency admission rates for the four conditions/services, and the percentage of patients with diabetes with glycated haemoglobin <7. There was no evidence that targeted marginal investments reduced emergency admission rates. There was evidence of an improvement in blood glucose management for diabetes for commissioners investing to improve diabetes care but this was compromised by a change in how the outcome was measured in different years. This investment was unlikely to be cost-effective. Commissioners made marginal investments in specific health conditions and services with the aim of improving a wide range of outcomes. There was little evidence of impact on the limited

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

PubMed

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.

Geoarchaeological evidence for dredging in Tyre's ancient harbour, Levant

NASA Astrophysics Data System (ADS)

Marriner, Nick; Morhange, Christophe

2006-01-01

Chrono-stratigraphic data from Tyre's ancient northern harbour delineate extensive dredging practices during the Greco-Roman and Byzantine periods. Radiocarbon dates from four cores consistently cluster between ca. 500 B.C. and 1000 A.D. and indicate rapid rates of sedimentation in the basin, namely ∼10 mm/yr during the Greco-Roman and Byzantine periods, compared to 0.5-1 mm/yr for the period 6000-4000 B.C. Absence of strata between 4000 B.C. and 500 B.C. is not consistent with a natural base-level sediment sink and cannot be interpreted as a depositional hiatus in the high-stand systems tract. Ancient dredging is further corroborated by persistent age-depth inversions within the fine-grained harbour facies. These data support removal of Middle Bronze Age to Persian period sediment strata, with deliberate overdeepening of the harbour bottom by Greco-Roman and Byzantine societies.

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.

PubMed

Serpell, M; Ratcliffe, S; Hovorka, J; Schofield, M; Taylor, L; Lauder, H; Ehler, E

2014-08-01

Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ(9) -tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study. In total, 303 patients with PNP associated with allodynia were screened; 128 were randomized to THC/CBD spray and 118 to placebo, in addition to their current analgesic therapy. The co-primary efficacy endpoints were the 30% responder rate in PNP 0-10 numerical rating scale (NRS) score and the mean change from baseline to the end of treatment in this score. Various key secondary measures of pain and functioning were also investigated. At the 30% responder level, there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis (intention-to-treat) dataset [p = 0.034; 95% confidence interval (CI): 1.05-3.70]. There was also a reduction in mean PNP 0-10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group, but which failed to reach statistical significance. Secondary measures of sleep quality 0-10 NRS score (p = 0.0072) and Subject Global Impression of Change (SGIC) (p = 0.023) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment. These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified. © 2014 European Pain Federation - EFIC®

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

PubMed Central

2014-01-01

Background 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. Methods 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. Results 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. Conclusions 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. Trial

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

NASA Astrophysics Data System (ADS)

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.

PubMed

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.

Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats

PubMed Central

Shen, Erica Y.; Ali, Syed F.; Meyer, Jerrold S.

2011-01-01

Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or “ecstasy”) also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ9-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5 mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA. PMID

Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.

PubMed

Shen, Erica Y; Ali, Syed F; Meyer, Jerrold S

2011-12-01

Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA. Published by

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

PubMed Central

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

A management system for accidental water pollution risk in a harbour: The Barcelona case study

NASA Astrophysics Data System (ADS)

Grifoll, Manel; Jordà, Gabriel; Espino, Manuel; Romo, Javier; García-Sotillo, Marcos

2011-10-01

Water quality degradation in harbour domains can have an important negative impact from an economic, touristic and environmental point of view. In that sense, water quality management is becoming a main concern for harbour managers. In this paper, we present the research behind the initiative started in Spanish harbours to control water quality degradation due to accidental pollution. This management system is already operationally running in the Barcelona harbour (NW Mediterranean Sea). The system is based on a recent published risk assessment, which takes into account not only the different activities in the harbour and their inherent risk of accident but also the physical behaviour of harbour waters. In this methodology, a key element is to get hydrodynamic forecasts. Thus, the system is composed of a hierarchy of nested hydrodynamic models covering from the basin scale to the harbour scale and a module that computes the different parameters needed for risk assessment. Special emphasis is made on describing the steps followed for system implementation because such implementation is far from a mere technical problem. The first step is to identify the main forcing factors for the harbour hydrodynamics from both field data and numerical experiments, which has never been done before for the Barcelona harbour. Wind and shelf currents are suggested as the main forcing factors for the harbour circulation. The second step is to identify the requirements that a numerical model must fulfil in order to properly solve the Barcelona harbour's hydrodynamics. A high resolution (< 50 m) three dimensional model able to prognostically calculate temperature and salinity evolution; full air-sea coupling is needed as well. The third step is to investigate the best operational strategy. We have found that small errors in the initial density profiles are acceptable for surface current forecasts but not for deep circulation. A cold start must be avoided and a 72 h spin-up is

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

PubMed

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.

75 FR 4783 - Federal Consistency Appeal by Villa Marina Yacht Harbour, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Federal Consistency Appeal by Villa Marina Yacht Harbour, Inc. AGENCY: National Oceanic and Atmospheric Administration (NOAA... days, closure of the decision record in an administrative appeal filed by Villa Marina Yacht Harbour...

Comparison between self-report of cannabis use and toxicological detection of THC/THCCOOH in blood and THC in oral fluid in drivers in a roadside survey.

PubMed

Van der Linden, Trudy; Silverans, Peter; Verstraete, Alain G

2014-01-01

The objective of this study was to compare the number of drivers who self-reported cannabis use by questionnaires to the results of toxicological analysis. During roadside surveys, 2957 respondents driving a personal car or van completed a questionnaire to report their use of drugs and medicines during the previous two weeks and to indicate the time of their last intake. Cannabis was analyzed in oral fluid by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), in blood by gas chromatography-mass spectrometry (GC-MS). Frequencies in the time categories were calculated and compared with toxicological results. Diagnostic values were calculated for the time categories in which positive findings were to be expected (<4 h and <2 4h, respectively for tetrahydrocannabinol (THC) and delta9-tetrahydrocannabinol (THCCOOH) in blood, <12 h for THC in oral fluid). Most self-reported cannabis use was more than 12 h before driving. The sensitivity of the questionnaire was low, while the specificity and accuracy were high. Kappa statistics revealed a fair agreement between self-report and positive findings for THC in oral fluid and blood and moderate agreement with THCCOOH in blood. Self-report largely underestimates driving under the influence of cannabis, particularly recent cannabis use; therefore analysis of biological samples is necessary. Copyright © 2013 John Wiley & Sons, Ltd.

Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?

PubMed

Maccarrone, Mauro; Maldonado, Rafael; Casas, Miguel; Henze, Thomas; Centonze, Diego

2017-04-01

The complexity of the endocannabinoid (eCB) system is becoming better understood and new drivers of eCB signaling are emerging. Modulation of the activities of the eCB system can be therapeutic in a number of diseases. Research into the eCB system has been paralleled by the development of agents that interact with cannabinoid receptors. In this regard it should be remembered that herbal cannabis contains a myriad of active ingredients, and the individual cannabinoids have quite distinct biological activities requiring independent studies. Areas covered: This article reviews the most important current data involving the eCB system in relation to human diseases, to reflect the present (based mainly on the most used prescription cannabinoid medicine, THC/CBD oromucosal spray) and potential future uses of cannabinoid-based therapy. Expert commentary: From the different therapeutic possibilities, THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity. Clinical trials have confirmed its efficacy and tolerability. Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer's disease, Parkinson's disease, Huntington's disease and epilepsy. The continued characterization of individual cannabinoids in different diseases remains important.

Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.

PubMed

Martin-Santos, R; Crippa, J A; Batalla, A; Bhattacharyya, S; Atakan, Z; Borgwardt, S; Allen, P; Seal, M; Langohr, K; Farré, M; Zuardi, A W; McGuire, P K

2012-01-01

Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p < 0.01), an increase in heart rate (p < 0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable. In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

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

PubMed

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.

28 CFR 16.201 - Voting by the Commissioners without joint deliberation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Voting by the Commissioners without joint deliberation. 16.201 Section 16.201 Judicial Administration DEPARTMENT OF JUSTICE PRODUCTION OR DISCLOSURE OF MATERIAL OR INFORMATION Public Observation of Parole Commission Meetings § 16.201 Voting by the...

A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.

PubMed

Sellers, Edward M; Schoedel, Kerri; Bartlett, Cindy; Romach, Myroslava; Russo, Ethan B; Stott, Colin G; Wright, Stephen; White, Linda; Duncombe, Paul; Chen, Chien-Feng

2013-07-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain. A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers. The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed. Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day. In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies. © The Author(s) 2013.

THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms.

PubMed

Trojano, Maria

2016-01-01

The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013. Web-based real-time data collection techniques are combined with traditional patients' diaries to capture a wide spectrum of outcomes associated with this innovative cannabis-based medication. After surpassing the recruitment threshold of 300 patients, an interim analysis was performed to determine whether the data collected to date align with those from MOVE 2-Germany and the largest phase III randomized controlled trial (RCT) of THC:CBD oromucosal spray. In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months' observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT. While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity. © 2016 S. Karger AG, Basel.

Biochemical indicators of pollution exposure in shorthorn sculpin (Myoxocephalus scorpius), caught in four harbours on the southwest coast of Iceland.

PubMed

Stephensen; Svavarsson; Sturve; Ericson; Adolfsson-Erici; Förlin

2000-04-01

Shorthorn sculpins (Myoxocephalus scorpius) were caught in four Icelandic harbours, differing in size, use and traffic. Biochemical responses in liver were measured and chemicals analysed in bile. Eyrarbakki harbour, which has not been in use for many years was chosen as a control site. Njar partial differentialvík harbour is a small fishing harbour and a marina, Sandger partial differentiali harbour is a large fishing harbour, and Reykjavík harbour is a large fishing harbour and an international transport harbour. Higher levels of DNA-adducts and cytochrome P4501A (CYP1A) in the fish from the harbours in Sandger partial differentiali, Njar partial differentialvík and Reykjavík, compared to Eyrarbakki harbour, indicate PAH exposure. This was confirmed by PAH analysis in bile. The higher activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in fish caught in Sandger partial differentiali, than in fish caught in the other harbours, indicate exposure of sculpin to prooxidative compounds in Sandger partial differentiali harbour. Shorthorn sculpin seems to be a convenient species for monitoring pollution in northern coastal areas.

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

PubMed

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.

Seasonal variation and sources of dissolved trace metals in Maó Harbour, Minorca Island.

PubMed

Martínez-Soto, Marly C; Tovar-Sánchez, Antonio; Sánchez-Quiles, David; Rodellas, Valentí; Garcia-Orellana, Jordi; Basterretxea, Gotzon

2016-09-15

The environmental conditions of semi-enclosed coastal water-bodies are directly related to the catchment, human activities, and oceanographic setting in which they are located. As a result of low tidal forcing, and generally weak currents, waters in Mediterranean harbours are poorly renewed, leading to quality deterioration. Here, we characterise the seasonal variation of trace metals (i.e. Co, Cd, Cu, Fe, Mo, Ni, Pb, and Zn) in surface waters, and trace metal content in sediments from Maó Harbour, a semi-enclosed coastal ecosystem in the NW Mediterranean Sea. Our results show that most of the dissolved trace metals in the waters of Maó Harbour exhibit a marked inner-outer concentration gradient, suggesting a permanent input into the inner part of the harbour. In general, metal concentrations in the waters of Maó Harbour are higher than those in offshore waters. Concentration of Cu (21±8nM), Fe (9.2±3.2nM) and Pb (1.3±0.4nM) are particularly high when compared with other coastal areas of the Mediterranean Sea. The concentration of some metals such as Cu and Zn increases during summertime, when the human population and boat traffic increase during the tourism season, and when resuspension from the metal enriched sediments is higher. The evaluation of the metal sources in the harbour reveals that, compared with other putative sources such as runoff, aerosol deposition and fresh groundwater discharges, contaminated sediments are the main source of the metals found in the water column, most likely through vessel-driven resuspension events. This study contributes to the understanding of the processes that control the occurrence and distribution of trace metals in Maó Harbour, thus aiding in the effective management of the harbour, and enhancing the overall quality of the seawater ecosystem. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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 (p<0.001) that was consistent with a schizophrenia-related phenotype, as well as potentiated changes in the NOR (p<0.01) and MWM (p<0.05) paradigms as compared to mice that received PCP alone. Decreased cortical receptor expression of NMDA receptor 1 subunit (NR1) was observed in mice that received PCP and PCP+Δ9-THC, while mice that received Δ9-THC and PCP+Δ9-THC displayed decreases in CB1 receptor expression. These findings suggest that administration of Δ9-THC during the early adulthood can potentiate the development of schizophrenia-related behavioral phenotypes induced by neonatal exposure to PCP in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

PubMed

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.

PubMed

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.

Influence of Previous Failed Antispasticity Therapy on the Efficacy and Tolerability of THC:CBD Oromucosal Spray for Multiple Sclerosis Spasticity.

PubMed

Haupts, Michael; Vila, Carlos; Jonas, Anna; Witte, Kerstin; Álvarez-Ossorio, Lourdes

2016-01-01

Sativex® (THC:CBD oromucosal spray) is indicated as add-on treatment for patients with moderate to severe multiple sclerosis (MS) spasticity. We aimed to determine whether antispasticity treatment history influenced the efficacy and safety of add-on THC:CBD oromucosal spray in MS spasticity patients. Post hoc analysis of an enriched-design clinical trial of THC:CBD oromucosal spray versus placebo, using records of patients under previous and current ineffective antispasticity therapies. Subgroups were patients with at least 1 failed therapy attempt with either baclofen or tizanidine (Group 1) or at least 2 failed therapy attempts with both baclofen and tizanidine (Group 2). Of 241 patients in the intent-to-treat population, 162 and 57 patients met the criteria for Groups 1 and 2, respectively. In all groups, response on the spasticity 0-10 Numerical Rating Scale was significantly greater with THC:CBD oromucosal spray versus placebo, for minimal clinically important difference (MCID ≥18% improvement vs. baseline) and clinically important difference (CID, ≥30% improvement vs. baseline). THC:CBD oromucosal spray improved spasticity-related symptoms such as sleep quality and timed 10-meter walk independent of the number of prior failed therapy attempts. Tolerability was not influenced by pre-treatment history. THC:CBD oromucosal spray provided consistent relief with good tolerability in MS spasticity patients irrespective of their antispasticity pre-treatment history. © 2016 S. Karger AG, Basel.

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

PubMed

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

Environmental assessment of metal exposure to corals living in Castle Harbour, Bermuda

USGS Publications Warehouse

Prouty, N.G.; Goodkin, N.F.; Jones, R.; Lamborg, C.H.; Storlazzi, C.D.; Hughen, K.A.

2013-01-01

Environmental contamination in Castle Harbour, Bermuda, has been linked to the dissolution and leaching of contaminants from the adjacent marine landfill. This study expands the evidence for environmental impact of leachate from the landfill by quantitatively demonstrating elevated metal uptake over the last 30 years in corals growing in Castle Harbour. Coral Pb/Ca, Zn/Ca and Mn/Ca ratios and total Hg concentrations are elevated relative to an adjacent control site in John Smith's Bay. The temporal variability in the Castle Harbour coral records suggests that while the landfill has increased in size over the last 35 years, the dominant input of metals is through periodic leaching of contaminants from the municipal landfill and surrounding sediment. Elevated contaminants in the surrounding sediment suggest that resuspension is an important transport medium for transferring heavy metals to corals. Increased winds, particularly during the 1990s, were accompanied by higher coral metal composition at Castle Harbour. Coupled with wind-induced resuspension, interannual changes in sea level within the Harbour can lead to increased bioavailability of sediment-bound metals and subsequent coral metal assimilation. At John Smith's Bay, large scale convective mixing may be driving interannual metal variability in the coral record rather than impacts from land-based activities. Results from this study provide important insights into the coupling of natural variability and anthropogenic input of contaminants to the nearshore environment.

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

PubMed

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 < 10-93 pg/mg for 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: < 10-17 pg/mg). Based on these results, it can be concluded that at least parts of the 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.

The federal government commissioner for patient issues in Germany: initial analysis of the user inquiries.

PubMed

Schneider, Nils; Dierks, Marie-Luise; Seidel, Gabriele; Schwartz, Friedrich W

2007-02-22

The political objective in many countries worldwide is to give better consideration to the interests of patients within the health system. The establishment of a federal government commissioner for the issues of patients in the health system in Germany in 2004 is part of these endeavours. The structure and field of activities of this institution has been unique so far. This study investigates for the first time the inquiries the commissioner receives from the public. A 33% sampling (n = 850) of the written inquiries (correspondence and e-mails) addressed to the commissioner in the first six months of the year 2005 (n = 2580) was investigated. In a procedure comprising combined qualitative and quantitative levels, the material was thematically encoded and the inquiries allocated to the resulting categories (multiple nominations). The results are presented in descriptive form and investigated especially with respect to sex and age-specific differences. The interdependences between the categorized criteria are analysed. The inquirers are equally spread out amongst the sexes (49% women, 51% men). Older persons outweigh the younger (69% over 60 years). In most cases the issues take the form of claims (72%, n = 609). In every fifth inquiry (n = 168) the personal financial burden for health services is considered as being too high; about equally high (n = 159) is the proportion of persons who criticize the communication with health professionals, especially hospitals and doctors' surgeries. Every third who mentions a medical practice uses terms such as "uncertainty" and "anxiety". It is conspicuous that men more often than women write that they feel unfairly treated in the health system (62% vs. 38%, p < 0.05). Predominantly older persons seek the assistance of the federal government commissioner for patient issues. Considerable uncertainty and anxiety with respect to services and charges within the system of the German health insurances become evident. It is not possible

The federal government commissioner for patient issues in Germany: initial analysis of the user inquiries

PubMed Central

Schneider, Nils; Dierks, Marie-Luise; Seidel, Gabriele; Schwartz, Friedrich W

2007-01-01

Background The political objective in many countries worldwide is to give better consideration to the interests of patients within the health system. The establishment of a federal government commissioner for the issues of patients in the health system in Germany in 2004 is part of these endeavours. The structure and field of activities of this institution has been unique so far. This study investigates for the first time the inquiries the commissioner receives from the public. Methods A 33% sampling (n = 850) of the written inquiries (correspondence and e-mails) addressed to the commissioner in the first six months of the year 2005 (n = 2580) was investigated. In a procedure comprising combined qualitative and quantitative levels, the material was thematically encoded and the inquiries allocated to the resulting categories (multiple nominations). The results are presented in descriptive form and investigated especially with respect to sex and age-specific differences. The interdependences between the categorized criteria are analysed. Results The inquirers are equally spread out amongst the sexes (49% women, 51% men). Older persons outweigh the younger (69% over 60 years). In most cases the issues take the form of claims (72%, n = 609). In every fifth inquiry (n = 168) the personal financial burden for health services is considered as being too high; about equally high (n = 159) is the proportion of persons who criticize the communication with health professionals, especially hospitals and doctors' surgeries. Every third who mentions a medical practice uses terms such as "uncertainty" and "anxiety". It is conspicuous that men more often than women write that they feel unfairly treated in the health system (62% vs. 38%, p < 0.05). Conclusion Predominantly older persons seek the assistance of the federal government commissioner for patient issues. Considerable uncertainty and anxiety with respect to services and charges within the system of the German health

28 CFR 2.24 - Review of panel recommendation by the Regional Commissioner.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Review of panel recommendation by the Regional Commissioner. 2.24 Section 2.24 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code...

28 CFR 2.24 - Review of panel recommendation by the Regional Commissioner.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Review of panel recommendation by the Regional Commissioner. 2.24 Section 2.24 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code...

A galenical produced from Ba-Wei-Die-Huang-Wan (THC-002) provides resistance to the cold stress-induced detrusor overactivity in conscious rats.

PubMed

Imamura, Tetsuya; Ishizuka, Osamu; Sudha, Gautam Silwal; Lei, Zhang; Hosoda, Tomoka; Noguchi, Wataru; Yamagishi, Takahiro; Yokoyama, Hitoshi; Kurizaki, Yoshiki; Nishizawa, Osamu

2013-06-01

We determined if THC-002, a galenical produced from Ba-Wei-Die-Huang-Wan, could increase skin temperature and inhibit detrusor overactivity induced by sudden whole body cooling. Further, we determined if THC-002 could decrease expression of transient receptor potential melastatin 8 (TRPM8) channels associated with the cold responses. Hind leg skin temperature of female 10-week-old Sprague-Dawley rats was measured by thermal imaging. Experimental rats (n = 12) were given oral 100 mg/kg THC-002 daily for one week, and controls (n = 12) were similarly treated with THC-002-free solution. Afterwards, thermal imaging and cystometric investigations of the freely moving conscious rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then transferred to a low temperature (LT, 4 ± 2°C) environment during which thermal imaging and cystometric measurements were taken at 5, 10, 20, 30, and 40 min. Afterward, the skin tissues were harvested to estimate expression levels of TRPM8 channels by immunohistochemistry and real-time reverse-transcription polymerase chain reaction. The RT skin temperature of THC-002-treated rats was significantly higher than controls. During the first 20 min under LT, the control rats exhibited cold stress-induced detrusor overactivity such as decreased voiding interval and bladder capacity. THC-002 partially inhibited the detrusor overactivity patterns. During the second 20 min, skin temperature was relatively stable, and the detrusor overactivity of both groups slowly disappeared. THC-002 significantly reduced expression of TRPM8 channel protein and mRNA. THC-002 inhibited cold stress-induced detrusor overactivity resulting from decreasing skin temperature. Therefore, THC-002 might provide resistance to cold stress-exacerbated lower urinary tract symptoms. Copyright © 2012 Wiley Periodicals, Inc.

How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia

PubMed Central

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.

2015-01-01

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. PMID:25031222

Effect of the psychoactive metabolite of marijuana, delta 9-tetrahydrocannabinol (THC), on the synthesis of tumor necrosis factor by human large granular lymphocytes.

PubMed

Kusher, D I; Dawson, L O; Taylor, A C; Djeu, J Y

1994-03-01

The natural killer cell (NK)/3polymorphonuclear neutrophil axis has recently been identified to be important in early defense against the opportunistic fungi, Candida albicans. Repression of this system is therefore likely to contribute to susceptibility to opportunistic infections. delta 9-Tetrahydrocannabinol (THC), an active constituent of marijuana, has been reported to be immunosuppressive at concentrations that exceed attainable plasma levels. In this report, we examine the possibility that human large granular lymphocytes (LGL) can be immunosuppressed by exposure to THC at physiologically relevant concentrations and probed two functions associated with LGL, i.e., cytokine production and tumoricidal activity. We find that these low levels of THC inhibit tumor necrosis factor-alpha (TNF) induction from LGL by C. albicans and are dependent upon THC dose (0.005-5.0 micrograms/ml) and length of exposure (0.05-3.0 hr). Northern blot analysis indicates that the downregulation of TNF production from LGL by THC resides at the mRNA level. Moreover, exposure of LGL to physiological THC concentrations (0.01-2.0 micrograms/ml) diminishes their cytolytic activity against K562 tumor cells.

Prescription for change: an interview with FDA Commissioner Dr. David Kessler.

PubMed

Kessler, D

1992-07-01

Dr David A. Kessler took over as Commissioner of the Food and Drug Administration in December 1990. Since then, he has initiated many changes to improve the structure and efficiency of the agency. In this interview, he describes some of the problems and challenges associated with the process of reviewing and approving new drugs.

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

PubMed

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

The modulation rate transfer function of a harbour porpoise (Phocoena phocoena).

PubMed

Linnenschmidt, Meike; Wahlberg, Magnus; Damsgaard Hansen, Janni

2013-02-01

During echolocation, toothed whales produce ultrasonic clicks at extremely rapid rates and listen for the returning echoes. The auditory brainstem response (ABR) duration was evaluated in terms of latency between single peaks: 5.5 ms (from peak I to VII), 3.4 ms (I-VI), and 1.4 ms (II-IV). In comparison to the killer whale and the bottlenose dolphin, the ABR of the harbour porpoise has shorter intervals between the peaks and consequently a shorter ABR duration. This indicates that the ABR duration and peak latencies are possibly related to the relative size of the auditory structures of the central nervous system and thus to the animal's size. The ABR to a sinusoidal amplitude modulated stimulus at 125 kHz (sensitivity threshold 63 dB re 1 μPa rms) was evaluated to determine the modulation rate transfer function of a harbour porpoise. The ABR showed distinct envelope following responses up to a modulation rate of 1,900 Hz. The corresponding calculated equivalent rectangular duration of 263 μs indicates a good temporal resolution in the harbour porpoise auditory system similar to the one for the bottlenose dolphin. The results explain how the harbour porpoise can follow clicks and echoes during echolocation with very short inter click intervals.

An innovative early warning system for floods and operational risks in harbours

NASA Astrophysics Data System (ADS)

Smets, Steven; Bolle, Annelies; Mollaert, Justine; Buitrago, Saul; Gruwez, Vincent

2016-04-01

Early Warning Systems (EWS) are nowadays becoming fairly standard in river flood forecasting or in large scale hydrometeorological predictions. For complex coastal morphodynamic problems or in the vicinity of complex coastal structures, such as harbours, EWS are much less used because they are both technically and computationally still very challenging. To advance beyond the state-of-the-art, the EU FP7 project Risc-KIT (www.risc-kit.eu) is developing prototype EWS which address specifically these topics. This paper describes the prototype EWS which IMDC has developed for the case study site of the harbour of Zeebrugge. The harbour of Zeebrugge is the largest industrial seaport on the coast of Belgium, extending more than 3 km into the sea. Two long breakwaters provide shelter for the inner quays and docks for regular conditions and frequent storms. Extreme storms surges and waves can however still enter the harbour and create risks for the harbour operations and infrastructure. The prediction of the effects of storm surges and waves inside harbours are typically very complex and challenging, due to the need of different types of numerical models for representing all different physical processes. In general, waves inside harbours are a combination of locally wind generated waves and offshore wave penetration at the port entrance. During extreme conditions, the waves could overtop the quays and breakwaters and flood the port facilities. Outside a prediction environment, the conditions inside the harbour could be assessed by superimposing processes. The assessment can be carried out by using a combination of a spectral wave model (i.e. SWAN) for the wind generated waves and a Boussinesq type wave model (i.e. Mike 21 BW) for the wave penetration from offshore. Finally, a 2D hydrodynamic model (i.e. TELEMAC) can be used to simulate the overland flooding inside the port facilities. To reproduce these processes in an EWS environment, an additional challenge is to cope

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

PubMed

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.

The Missing Elements of Change. A Response to "Youth Change Agents: Comparing the Sociopolitical Identities of Youth Organizers and Youth Commissioners"

ERIC Educational Resources Information Center

Goldwasser, Matthew L.

2016-01-01

By establishing a set of theoretical frameworks to view and compare the work of youth organizers and youth commissioners, and through personal interviews, the authors of the paper "Youth Change Agents: Comparing the Sociopolitical Identities of Youth Organizers and Youth Commissioners" presented their explanation of the development of…

The effect of Kingston Harbour outflow on the zooplankton populations of Hellshire, south-east coast, Jamaica

NASA Astrophysics Data System (ADS)

Lindo, Mona K.

1991-06-01

Zooplankton sampling was conducted at 16 stations located at the mouth of Kingston Harbour and throughout the Hellshire area from November 1985 to March 1987. Parameters examined included total biomass, total numbers and numbers of numerically important zooplankton species. Maximum values were recorded west of the Harbour mouth (station 1) and these gradually decreased with distance from the Harbour especially at the 'offshore' stations, producing a gradient effect in this area. Mean biomass and abundance for the period sampled ranged from 14 g m -3 and 16 313 individuals m -3 at the western side of the Harbour mouth to 0·4 g m -3 and 172 individuals m -3 at Wreck Reef. Stations within the bays of Hellshire occasionally had values similar to those recorded at the mouth of Kingston Harbour and here there was less evidence of a gradual decline. Considerable monthly fluctuation occurred in these parameters but there was no discernible seasonal pattern. Copepods dominated the population at most stations and the sergestid Lucifer faxoni also proved an important member at the western Harbour mouth station.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

THC reduces the anticipatory nucleus accumbens response to reward in subjects with a nicotine addiction

PubMed Central

Jansma, J M; van Hell, H H; Vanderschuren, L J M J; Bossong, M G; Jager, G; Kahn, R S; Ramsey, N F

2013-01-01

Recent evidence has implicated the endocannabinoid (eCB) system in nicotine addiction. The eCB system also has an important role in reward mechanisms, and nicotine addiction has been associated with aberrant reward processing. Motivated by this evidence, we tested the hypothesis that eCB modulation of reward processing is altered in subjects with a nicotine addiction (NAD). For this purpose, we compared reward-related activity in NAD with healthy controls (HC) in a pharmacological magnetic resonance imaging (MRI) study using Δ9-tetrahydrocannabinol (THC) administration to challenge the eCB system. Eleven HC and 10 NAD participated in a 3-T functional MRI (fMRI) study with a double-blind, cross-over, placebo-controlled design, using a Monetary Incentive Delay (MID) paradigm with three reward levels. Reward activity in the nucleus accumbens (NAcc) and caudate putamen during anticipation and feedback of reward was compared after THC and placebo. fMRI results indicated a significant reduction of reward anticipation activity in the NAcc in NAD after THC administration, which was not present in HC. This is indicated by a significant group by drug by reward interaction. Our data show that THC significantly reduces the NAcc response to monetary reward anticipation in NAD. These results suggest that nicotine addiction is associated with altered eCB modulation of reward processing in the NAcc. This study adds important human data to existing evidence implicating the eCB system in nicotine addiction. PMID:23443360

Phocine distemper virus (PDV) seroprevalence as predictor for future outbreaks in harbour seals.

PubMed

Ludes-Wehrmeister, Eva; Dupke, Claudia; Harder, Timm C; Baumgärtner, Wolfgang; Haas, Ludwig; Teilmann, Jonas; Dietz, Rune; Jensen, Lasse F; Siebert, Ursula

2016-02-01

Phocine distemper virus (PDV) infections caused the two most pronounced mass mortalities in marine mammals documented in the past century. During the two outbreaks, 23,000 and 30,000 harbour seals (Phoca vitulina), died in 1988/1989 and 2002 across populations in the Wadden Sea and adjacent waters, respectively. To follow the mechanism and development of disease spreading, the dynamics of Morbillivirus-specific antibodies in harbour seal populations in German and Danish waters were examined. 522 serum samples of free-ranging harbour seals of different ages were sampled between 1990 and 2014. By standard neutralisation assays, Morbillivirus-specific antibodies were detected, using either the PDV isolate 2558/Han 88 or the related canine distemper virus (CDV) strain Onderstepoort. A total of 159 (30.5%) of the harbour seals were seropositive. Annual seroprevalence rates showed an undulating course: Peaks were seen in the post-epidemic years 1990/1991 and 2002/2003. Following each PDV outbreak, seroprevalence decreased and six to eight years after the epidemics samples were tested seronegative, indicating that the populations are now again susceptible to new PDV outbreak. After the last outbreak in 2002, the populations grew steadily to an estimated maximum (since 1975) of about 39,100 individuals in the Wadden Sea in 2014 and about 23,540 harbour seals in the Kattegat area in 2013. A re-appearence of PDV would presumably result in another epizootic with high mortality rates as encountered in the previous outbreaks. The current high population density renders harbour seals vulnerable to rapid spread of infectious agents including PDV and the recently detected influenza A virus. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

Endocannabinoid signaling at the periphery: 50 years after THC

PubMed Central

Maccarrone, Mauro; Bab, Itai; Bíró, Tamás; Cabral, Guy A.; Dey, Sudhansu K.; Di Marzo, Vincenzo; Konje, Justin C.; Kunos, George; Mechoulam, Raphael; Pacher, Pal; Sharkey, Keith A.; Zimmer, Andreas

2015-01-01

Fifty years ago (in 1964) the psychoactive ingredient of Cannabis sativa, Δ9-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide, AEA) in 1992, and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize and degrade them, and that altogether form the eCB system. eCBs control basic biological processes, including cell-choice between survival and death, and progenitor/stem cell proliferation and differentiation. Not surprisingly, in the past two decades, eCBs have been recognized as key mediators of several aspects of human pathophysiology, and thus have emerged among the most widespread and versatile signaling molecules ever discovered. Here, some of the pioneers of this research field review the state-of-the-art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral eCB system for human health and disease pathogenesis, as well as to highlight emerging challenges and therapeutic hopes. PMID:25796370

Endocannabinoid signaling at the periphery: 50 years after THC.

PubMed

Maccarrone, Mauro; Bab, Itai; Bíró, Tamás; Cabral, Guy A; Dey, Sudhansu K; Di Marzo, Vincenzo; Konje, Justin C; Kunos, George; Mechoulam, Raphael; Pacher, Pal; Sharkey, Keith A; Zimmer, Andreas

2015-05-01

In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize, and degrade them and that together form the eCB system (ECS). eCBs control basic biological processes including cell choice between survival and death and progenitor/stem cell proliferation and differentiation. Unsurprisingly, in the past two decades eCBs have been recognized as key mediators of several aspects of human pathophysiology and thus have emerged to be among the most widespread and versatile signaling molecules ever discovered. Here some of the pioneers of this research field review the state of the art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes. Copyright © 2015 Elsevier Ltd. All rights reserved.

A THC Simulator for Modeling Fluid-Rock Interactions

NASA Astrophysics Data System (ADS)

Hamidi, Sahar; Galvan, Boris; Heinze, Thomas; Miller, Stephen

2014-05-01

Fluid-rock interactions play an essential role in many earth processes, from a likely influence on earthquake nucleation and aftershocks, to enhanced geothermal system, carbon capture and storage (CCS), and underground nuclear waste repositories. In THC models, two-way interactions between different processes (thermal, hydraulic and chemical) are present. Fluid flow influences the permeability of the rock especially if chemical reactions are taken into account. On one hand solute concentration influences fluid properties while, on the other hand, heat can affect further chemical reactions. Estimating heat production from a naturally fractured geothermal systems remains a complex problem. Previous works are typically based on a local thermal equilibrium assumption and rarely consider the salinity. The dissolved salt in fluid affects the hydro- and thermodynamical behavior of the system by changing the hydraulic properties of the circulating fluid. Coupled thermal-hydraulic-chemical models (THC) are important for investigating these processes, but what is needed is a coupling to mechanics to result in THMC models. Although similar models currently exist (e.g. PFLOTRAN), our objective here is to develop algorithms for implementation using the Graphics Processing Unit (GPU) computer architecture to be run on GPU clusters. To that aim, we present a two-dimensional numerical simulation of a fully coupled non-isothermal non-reactive solute flow. The thermal part of the simulation models heat transfer processes for either local thermal equilibrium or nonequilibrium cases, and coupled to a non-reactive mass transfer described by a non-linear diffusion/dispersion model. The flow process of the model includes a non-linear Darcian flow for either saturated or unsaturated scenarios. For the unsaturated case, we use the Richards' approximation for a mixture of liquid and gas phases. Relative permeability and capillary pressure are determined by the van Genuchten relations

76 FR 13111 - Compassionate Allowances for Autoimmune Disease, Office of the Commissioner; Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

..., schizophrenia, and cardiovascular disease and multiple organ transplants, respectively. We will hold our next...] Compassionate Allowances for Autoimmune Disease, Office of the Commissioner; Hearing AGENCY: Social Security... Compassionate Allowance public hearings to help us identify the diseases and other serious medical conditions...

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.

PubMed

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).

PubMed

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

NASA Astrophysics Data System (ADS)

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.

Pressure-induced structural transformations and polymerization in ThC2.

PubMed

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

2017-04-06

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 (ThC 2 ) 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 ThC 2 .

26 CFR 1.148-10 - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2013 CFR

2013-04-01

... outweighed by other factors, however, such as bona fide cost underruns or long-term financial distress. (b... refund other long-term, non-callable bonds in the same refunding issue. There are no savings attributable... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Anti-abuse rules and authority of Commissioner...

26 CFR 1.148-10 - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... outweighed by other factors, however, such as bona fide cost underruns or long-term financial distress. (b... refund other long-term, non-callable bonds in the same refunding issue. There are no savings attributable... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Anti-abuse rules and authority of Commissioner...

26 CFR 1.148-10 - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... outweighed by other factors, however, such as bona fide cost underruns or long-term financial distress. (b... refund other long-term, non-callable bonds in the same refunding issue. There are no savings attributable... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Anti-abuse rules and authority of Commissioner...

26 CFR 1.148-10 - Anti-abuse rules and authority of Commissioner.

Code of Federal Regulations, 2011 CFR

2011-04-01

... outweighed by other factors, however, such as bona fide cost underruns or long-term financial distress. (b... refund other long-term, non-callable bonds in the same refunding issue. There are no savings attributable... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Anti-abuse rules and authority of Commissioner...

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

PubMed

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 Δ9-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys

PubMed Central

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

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

PubMed

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.

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.

PubMed

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 (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure THCV or placebo were administered daily for five days, followed by 1mg intravenous 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.

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

PubMed

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.

PubMed

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.

Impaired Functional Connectivity of Brain Reward Circuitry in Patients with Schizophrenia and Cannabis Use Disorder: Effects of Cannabis and THC

PubMed Central

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

2016-01-01

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 15mg 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. PMID:25037524

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.

PubMed

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.

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

PubMed Central

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

2014-01-01

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 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg 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 10 mg THC + 0 mg, 10 mg, 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. PMID:25175495

Deciphering natural to anthropogenic control on sedimentation: the Late Holocene Magdala (Kinneret Lake, Israel) harbour hystory

NASA Astrophysics Data System (ADS)

Sarti, G.; Rossi, V.; Amorosi, A.; Bertoni, D.; Ribolini, A.; Sammartino, I.; Zanchetta, G.

2012-04-01

Using a multidisciplinary approach involving geologists, geomorphologists and archeologists, the late Holocene sedimentary succession buried beneath the ancient Magdala harbour area (Kinneret Lake, Israel) was studied, in order to highlight the strict relationships among harbour evolutive phases (e.g. foundation, siltation, abandonment), natural events (e.g. sea-level variations, climatic changes and earthquakes among the most important) and, obviously, archaeological history. Recent excavations performed within the "Magdala Project" have discovered a harbour structure with late Hellenistic-Roman mooring stones at altitudes of 208.100 m and 208.320 m bsl respectively, suggestive of a higher lake-level (about 212 m bsl) than previously hypothesized. Along the most representative sections of trenches, integrated sedimentological, micropalaeontological (benthic meiofauna and pollen) and geochemical analyses were carried out on sedimentary deposits underlying and overlying the harbour structures, to define the main depositional facies and evolution phases that took place during the last millennia. Spatial variability of coeval palaeoenvironments across the archaeological site allowed to reconstruct a comprehensive picture of the harbour complex, evidencing the occurrence of three main evolution phases, similar to those reported from several Mediterranean Sea harbour systems: 1) a pre-harbor foundation phase; 2) a sin-harbor activity phase and 3) an harbor-abandonment phase. The first phase corresponds to the development of a natural lacustrine sandy beach barren in archaeological remains and containing an ostracod fauna very similar to the one observed within the present-day lake basin at ca. 5 m water depth. The second phase was characterized by the formation of an early Hellenistic sheltered lacustrine basin, recording the first anthropogenic control exerted on coastal sedimentation by the construction of harbour structures ("anthropogenically forced sheltered basin

Detection and effects of harmful algal toxins in Scottish harbour seals and potential links to population decline.

PubMed

Jensen, Silje-Kristin; Lacaze, Jean-Pierre; Hermann, Guillaume; Kershaw, Joanna; Brownlow, Andrew; Turner, Andrew; Hall, Ailsa

2015-04-01

Over the past 15 years or so, several Scottish harbour seal (Phoca vitulina) populations have declined in abundance and several factors have been considered as possible causes, including toxins from harmful algae. Here we explore whether a link could be established between two groups of toxins, domoic acid (DA) and saxitoxins (STXs), and the decline in the harbour seal populations in Scotland. We document the first evidence that harbour seals are exposed to both DA and STXs from consuming contaminated fish. Both groups of toxins were found in urine and faeces sampled from live captured (n = 162) and stranded animals (n = 23) and in faecal samples collected from seal haul-out sites (n = 214) between 2008 and 2013. The proportion of positive samples and the toxins levels measured in the excreta were significantly higher in areas where harbour seal abundance is in decline. There is also evidence that DA has immunomodulatory effects in harbour seals, including lymphocytopenia and monocytosis. Scottish harbour seals are exposed to DA and STXs through contaminated prey at potentially lethal levels and with this evidence we suggest that exposure to these toxins are likely to be important factors driving the harbour seal decline in some regions of Scotland. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Solid-phase extraction and GC-MS analysis of THC-COOH method optimized for a high-throughput forensic drug-testing laboratory.

PubMed

Stout, P R; Horn, C K; Klette, K L

2001-10-01

In order to facilitate the confirmation analysis of large numbers of urine samples previously screened positive for delta9-tetrahydrocannabinol (THC), an extraction, derivitization, and GC-MS analysis method was developed. This method utilized a positive pressure manifold anion-exchange polymer-based solid-phase extraction followed by elution directly into the automated liquid sampling (ALS) vials. Rapid derivitization was accomplished using pentafluoropropionic anhydride/pentafluoropropanol (PFPA/PFPOH). Recoveries averaged 95% with a limit of detection of 0.875 ng/mL with a 3-mL sample volume. Performance of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH)-d3 and THC-COOH-d9 internal standards were evaluated. The method was linear to 900 ng/mL THC-COOH using THC-COOH-d9 with negligible contribution from the internal standard to very weak samples. Excellent agreement was seen with previous quantitations of human urine samples. More than 1000 human urine samples were analyzed using the method with 300 samples analyzed using an alternate qualifier ion (m/z 622) after some interference was observed with a qualifier ion (m/z 489). The 622 ion did not exhibit any interference even in samples with interfering peaks present in the 489 ion. The method resulted in dramatic reductions in processing time, waste production, and exposure hazards to laboratory personnel.

Stereotypical rapid source level regulation in the harbour porpoise biosonar

NASA Astrophysics Data System (ADS)

Linnenschmidt, Meike; Kloepper, Laura N.; Wahlberg, Magnus; Nachtigall, Paul E.

2012-09-01

Some odontocetes and bats vary both click intensity and receiver sensitivity during echolocation, depending on target range. It is not known how this so-called automatic gain control is regulated by the animal. The source level of consecutive echolocation clicks from a harbour porpoise was measured with a hydrophone array while the animal detected an aluminium cylinder at 2, 4 or 8 m distance in a go/no-go paradigm. On-axis clicks had source levels of 145-174 dB re 1 μPa peak-to-peak. During target-present trials the click trains reached comparable source levels independent of the range to the target after three clicks. After an additional click, the source level was reduced for the 2 and 4 m trials until it equalled the one-way transmission loss. During target-absent trials, the source level remained high throughout the entire click train. Given typical values of harbour porpoise inter-click intervals, the source level reduction commenced within a few 100 ms from the first click in the click train. This may indicate a sub-cortically regulated source level regulation in the harbour porpoise.

Stereotypical rapid source level regulation in the harbour porpoise biosonar.

PubMed

Linnenschmidt, Meike; Kloepper, Laura N; Wahlberg, Magnus; Nachtigall, Paul E

2012-09-01

Some odontocetes and bats vary both click intensity and receiver sensitivity during echolocation, depending on target range. It is not known how this so-called automatic gain control is regulated by the animal. The source level of consecutive echolocation clicks from a harbour porpoise was measured with a hydrophone array while the animal detected an aluminium cylinder at 2, 4 or 8 m distance in a go/no-go paradigm. On-axis clicks had source levels of 145-174 dB re 1 μPa peak-to-peak. During target-present trials the click trains reached comparable source levels independent of the range to the target after three clicks. After an additional click, the source level was reduced for the 2 and 4 m trials until it equalled the one-way transmission loss. During target-absent trials, the source level remained high throughout the entire click train. Given typical values of harbour porpoise inter-click intervals, the source level reduction commenced within a few 100 ms from the first click in the click train. This may indicate a sub-cortically regulated source level regulation in the harbour porpoise.

Understanding coastal processes to assist with coastal erosion management in Darwin Harbour, Northern Territory, Australia

NASA Astrophysics Data System (ADS)

Tonyes, S. G.; Wasson, R. J.; Munksgaard, N. C.; Evans, K. G.; Brinkman, R.; Williams, D. K.

2017-02-01

Sand transport pathways in Darwin Harbour, Northern Territory, Australia, are being investigated to assist with coastal management. Coastal erosion, which threatens public and private infrastructure, is one of the major problems along the harbour beaches. A study of sediment transport is essential to identify the challenges encountered by the stakeholders in coastal management. Darwin Harbour, located in the tropical, cyclone prone area of Australia, was, until recently, considered a near pristine estuary. A semi-diurnal macro-tidal embayment, the tidal variation in the harbour reaches up to 8 m with a mean tidal range of 3.7 m. The beach morphology consists of sandy pocket beaches between coastal cliffs, sandbars, rocky shore platforms, tidal flats and mangrove fringes. A two-dimensional depth averaged finite-element hydrodynamic model (RMA-2), coupled with a sediment transport model (RMA-11) from Resource Modelling Associates, has been used to infer the sources and the depositional areas of sand in the harbour. Grain size distributions and geochemical analysis are also used to characterize the sand and its source(s). Initial results show that the beach sand is mostly of offshore origin with small sand input from the rivers. Potential supplementary sand sources are the eroded materials from the shore platforms and the rocky cliffs. Due to the rapid development in Darwin Harbour, this study is fundamental in understanding coastal processes to support decision making in coastal management, particularly in a macro-tidal, tropical estuary.

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

PubMed

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.

PubMed

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.

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

PubMed Central

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

2014-01-01

Background and PurposeMany 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 Δ9-tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. Experimental ApproachMale 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. Key ResultsTHC 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. Conclusions and ImplicationsAdolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. Linked ArticlesThis 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 PMID:24236988

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

PubMed

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.

Macro- and meiofaunal community features in the critical environmental system of a tourist harbour (Rapallo, Ligurian Sea, NW Mediterranean).

PubMed

Harriague, Anabella Covazzi; Albertelli, Giancarlo; Misic, Cristina

2012-03-01

Two samplings were carried out in a tourist harbour, during low and high touristic activity periods, to study the macro- and meiofaunal communities in relation to the environmental features. A multivariate analysis showed close relationships: the maritime traffic disturbance and the food quality and availability drive the spatial differences of the assemblages, dividing the area into three sub-areas: the area near the Boate torrent that empties into the harbour, the harbour proper, and the external area (just outside the harbour). Macro- and meiofauna showed notably different temporal trends, indicating competition for the resources and the higher sensitivity of the macrofauna to environmental pressures. The macrofauna strongly decreased as a response to heavier harbour activities, with increasing turbidity also affecting the external station outside the harbour. Finally, comparing the macrofaunal communities to those sampled in the same area 10 years before, we found that their abundance, richness and biomass had notably decreased, highlighting the worsening of the harbour environment due to the increased organic load and turbidity. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

PubMed

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)

Opportunities to learn from medical incidents: a review of published reports from the Health and Disability Commissioner.

PubMed

Temelkovski, Sara; Callaghan, Kathleen

2010-05-14

To analyse recent published information about the Health and Disability Commissioner's investigations in the context of The New Zealand Medical Council's Domains of Competence and investigate possible relationships. Retrospective review of 100 recent Health and Disability Commissioner (HDC) investigations published online (all cases reviewed regardless of the Commissioner's 'verdict'), involving at least one medical practitioner. Breaches and issues raised were categorised according to the Domains of Competence set by the Medical Council of New Zealand. The most common area of competence identified in the HDC investigations was that of Medical Expert, in 92.9% of cases. The second was Communication, identified in 48.7% of cases. Many cases included more than one Domain of Competence, with an average of 1.8 domains per investigation. Further characteristics of the cases were examined and a number of medical practitioner, patient, setting and timing statistics are also presented. This study finds medical expertise and communication skills to be the key areas of a medical practitioner's role that public complaints address. Beyond this, the limited data available through the Commissioner's published reports make it difficult to draw conclusions which might assist with the improvement of medical practice in New Zealand. We therefore conclude that the data available is useful only at a case-by-case level. More extensive use of published information about incidents involving medical practitioners will have to await changes to provide for the systematic reporting of a much higher proportion of incident investigations. Given New Zealand's current environment for dealing with medical complaints, this may require changes beyond the area of consumer complaint investigations considered here.

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

PubMed

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.

21 CFR 71.27 - Listing and exemption from certification on the Commissioner's initiative.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Listing and exemption from certification on the Commissioner's initiative. 71.27 Section 71.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS Administrative Action on Petitions § 71.27...

21 CFR 71.27 - Listing and exemption from certification on the Commissioner's initiative.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Listing and exemption from certification on the Commissioner's initiative. 71.27 Section 71.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS Administrative Action on Petitions § 71.27...

21 CFR 71.27 - Listing and exemption from certification on the Commissioner's initiative.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Listing and exemption from certification on the Commissioner's initiative. 71.27 Section 71.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS Administrative Action on Petitions § 71.27...

Pressure-induced structural transformations and polymerization in ThC2

PubMed Central

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

2017-01-01

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. PMID:28383571

Year-round spatiotemporal distribution of harbour porpoises within and around the Maryland wind energy area

PubMed Central

O’Brien, Michael; Lyubchich, Vyacheslav; Roberts, Jason J.; Halpin, Patrick N.; Rice, Aaron N.; Bailey, Helen

2017-01-01

Offshore windfarms provide renewable energy, but activities during the construction phase can affect marine mammals. To understand how the construction of an offshore windfarm in the Maryland Wind Energy Area (WEA) off Maryland, USA, might impact harbour porpoises (Phocoena phocoena), it is essential to determine their poorly understood year-round distribution. Although habitat-based models can help predict the occurrence of species in areas with limited or no sampling, they require validation to determine the accuracy of the predictions. Incorporating more than 18 months of harbour porpoise detection data from passive acoustic monitoring, generalized auto-regressive moving average and generalized additive models were used to investigate harbour porpoise occurrence within and around the Maryland WEA in relation to temporal and environmental variables. Acoustic detection metrics were compared to habitat-based density estimates derived from aerial and boat-based sightings to validate the model predictions. Harbour porpoises occurred significantly more frequently during January to May, and foraged significantly more often in the evenings to early mornings at sites within and outside the Maryland WEA. Harbour porpoise occurrence peaked at sea surface temperatures of 5°C and chlorophyll a concentrations of 4.5 to 7.4 mg m-3. The acoustic detections were significantly correlated with the predicted densities, except at the most inshore site. This study provides insight into previously unknown fine-scale spatial and temporal patterns in distribution of harbour porpoises offshore of Maryland. The results can be used to help inform future monitoring and mitigate the impacts of windfarm construction and other human activities. PMID:28467455

Year-round spatiotemporal distribution of harbour porpoises within and around the Maryland wind energy area.

PubMed

Wingfield, Jessica E; O'Brien, Michael; Lyubchich, Vyacheslav; Roberts, Jason J; Halpin, Patrick N; Rice, Aaron N; Bailey, Helen

2017-01-01

Offshore windfarms provide renewable energy, but activities during the construction phase can affect marine mammals. To understand how the construction of an offshore windfarm in the Maryland Wind Energy Area (WEA) off Maryland, USA, might impact harbour porpoises (Phocoena phocoena), it is essential to determine their poorly understood year-round distribution. Although habitat-based models can help predict the occurrence of species in areas with limited or no sampling, they require validation to determine the accuracy of the predictions. Incorporating more than 18 months of harbour porpoise detection data from passive acoustic monitoring, generalized auto-regressive moving average and generalized additive models were used to investigate harbour porpoise occurrence within and around the Maryland WEA in relation to temporal and environmental variables. Acoustic detection metrics were compared to habitat-based density estimates derived from aerial and boat-based sightings to validate the model predictions. Harbour porpoises occurred significantly more frequently during January to May, and foraged significantly more often in the evenings to early mornings at sites within and outside the Maryland WEA. Harbour porpoise occurrence peaked at sea surface temperatures of 5°C and chlorophyll a concentrations of 4.5 to 7.4 mg m-3. The acoustic detections were significantly correlated with the predicted densities, except at the most inshore site. This study provides insight into previously unknown fine-scale spatial and temporal patterns in distribution of harbour porpoises offshore of Maryland. The results can be used to help inform future monitoring and mitigate the impacts of windfarm construction and other human activities.

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

PubMed

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

Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)*

PubMed Central

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.

2015-01-01

Δ9-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. PMID:25666611

tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule.

PubMed

2017-11-22

This final rule adopts without changes an interim final rule with request for comments published in the Federal Register on March 23, 2017. 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. The Drug Enforcement Administration (DEA) maintains FDA-approved products of oral solutions containing dronabinol in schedule II of the Controlled Substances Act.

78 FR 32306 - Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... DEPARTMENT OF THE TREASURY Internal Revenue Service Advisory Group to the Commissioner of Internal Revenue; Renewal of Charter AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice. SUMMARY: The... Communications and Liaison, 202-283-8868 (not a toll-free number). SUPPLEMENTARY INFORMATION: Notice is hereby...

75 FR 22126 - Notice of Commissioner and Staff Attendance at WIRAB and CREPC Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-27

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at WIRAB and CREPC Meetings April 20, 2010. The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and/or Commission staff may attend the following meetings: April 21...

STS-33 MS Carter operates translation hand control (THC) on aft flight deck

NASA Technical Reports Server (NTRS)

1989-01-01

STS-33 Mission Specialist (MS) Manley L. Carter, Jr operates translation hand control (THC) at the aft flight deck onorbit station while peering out overhead window W7. Carter's communications kit assembly headset microphone extends across his face.

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

PubMed

Verhoeckx, Kitty C M; Korthout, Henrie A A J; van Meeteren-Kreikamp, A P; Ehlert, Karl A; Wang, Mei; van der Greef, Jan; Rodenburg, Richard J T; Witkamp, Renger F

2006-04-01

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 extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.

Why do seals have cones? Behavioural evidence for colour-blindness in harbour seals.

PubMed

Scholtyssek, Christine; Kelber, Almut; Dehnhardt, Guido

2015-03-01

All seals and cetaceans have lost at least one of two ancestral cone classes and should therefore be colour-blind. Nevertheless, earlier studies showed that these marine mammals can discriminate colours and a colour vision mechanism has been proposed which contrasts signals from cones and rods. However, these earlier studies underestimated the brightness discrimination abilities of these animals, so that they could have discriminated colours using brightness only. Using a psychophysical discrimination experiment, we showed that a harbour seal can solve a colour discrimination task by means of brightness discrimination alone. Performing a series of experiments in which two harbour seals had to discriminate the brightness of colours, we also found strong evidence for purely scotopic (rod-based) vision at light levels that lead to mesopic (rod-cone-based) vision in other mammals. This finding speaks against rod-cone-based colour vision in harbour seals. To test for colour-blindness, we used a cognitive approach involving a harbour seal trained to use a concept of same and different. We tested this seal with pairs of isoluminant stimuli that were either same or different in colour. If the seal had perceived colour, it would have responded to colour differences between stimuli. However, the seal responded with "same", providing strong evidence for colour-blindness.

Modelling the tsunami threat to Sydney Harbour, Australia, with comparisons to historical events.

NASA Astrophysics Data System (ADS)

Wilson, O.; Power, H.

2016-12-01

Sydney Harbour is an iconic location with a dense population and low-lying development. On the east coast of Australia, facing the Pacific Ocean it is exposed to several tsunamigenic trenches. To date, this is the most detailed assessment of the potential for earthquake-generated tsunami impact on Sydney Harbour. The tsunami wave trains modelled include tsunami modelled from earthquakes of magnitude 7.5, 8.0, 8.5 and 9.0 MW from the Puysegur and New Hebrides trenches. Historical events from Chile in 1960 and Japan in 2011 are also modelled for comparison. Using the hydrodynamic model ANUGA, results show that the events modelled have the potential to cause high current speeds, hazardous waves and rapid changes in water level. These effects are most dramatic at pinch points such as Spit Bridge and Anzac Bridge, particularly with regard to current speeds. Large waves are shown to be a particular threat at the mouth of the harbour, where the bathymetry causes the tsunami wave train to shoal. Inundation is less of a hazard for the tsunami events modlled, although some inundation is evident at several low-lying embayments in the south of the harbour. These results will provide an evidence base for tsunami threat emergency management.

75 FR 70932 - Office of the Commissioner of Food and Drugs; Delegation of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-19

... exercise of the authorities delegated herein prior to the effective date of this delegation. This... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Office of the Secretary... delegated to the Commissioner of Food and Drugs the authorities vested in the Secretary of Health and Human...

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.

PubMed

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.

PubMed

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.

PubMed

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.

A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers.

PubMed

Stott, Colin; White, Linda; Wright, Stephen; Wilbraham, Darren; Guy, Geoffrey

2013-12-01

This Phase I study aimed to assess the potential drug-drug interactions (pharmacokinetic [PK] and safety profile) of Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (Sativex (®), nabiximols) in combination with cytochrome P450 (CYP450) inducer (rifampicin) or inhibitors (ketoconazole or omeprazole). Thirty-six healthy male subjects were divided into three groups of 12, and then randomized to one of two treatment sequences per group. Subjects received four sprays of THC/CBD (10.8/10 mg) alongside single doses of the CYP3A and 2C19 inducer rifampicin (600 mg), CYP3A inhibitor ketoconazole (400 mg) or CYP2C19 inhibitor omeprazole (40 mg). Plasma samples were analyzed for CBD, THC and its metabolite 11-hydroxy-THC (11-OH-THC). A single dose of four sprays of THC/CBD spray (10.8/10 mg) following repeated doses of rifampicin (600 mg) reduced the Cmax and AUC of all analytes. Cmax reduced from 2.94 to 1.88 ng/mL (-36%), 1.03 to 0.50 ng/mL (-52%) and 3.38 to 0.45 ng/mL (-87%) for THC, CBD and 11-OH-THC, respectively compared to single dose administration of THC/CBD spray alone. Ketoconazole co-administration with THC/CBD spray had the opposite effect, increasing the Cmax of the respective analytes from 2.65 to 3.36 ng/mL (+27%), 0.66 to 1.25 ng/mL (+89%) and 3.59 to 10.92 ng/mL (+204%). No significant deviations in Cmax or AUC for any analyte were observed when THC/CBD spray was co-administered with omeprazole. THC/CBD spray was well tolerated by the study subjects both alone and in combination with rifampicin, ketoconazole and omeprazole. Evaluation of the PKs of THC/CBD spray alone and in combination with CYP450 inhibitors/inducers suggests that all analytes are substrates for the isoenzyme CYP3A4, but not CYP2C19. On the basis of our findings, there is likely to be little impact on other drugs metabolized by CYP enzymes on the PK parameters of THC/CBD spray, but potential effects should be taken into consideration when co-administering THC/CBD spray

77 FR 47051 - Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation Meetings The Federal Energy Regulatory Commission (Commission) hereby gives notice that members of the Commission and/or Commission staff may attend...

76 FR 66924 - Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-28

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation Meetings The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and/or Commission staff may attend the...

77 FR 24946 - Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation Meetings The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and/or Commission staff may attend the...

76 FR 28024 - Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation Meetings The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and/or Commission staff may attend the...

77 FR 6112 - Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation Meetings The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and/or Commission staff may attend the...

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

PubMed

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.

PubMed

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.

Field studies: Test method for on-line continuous measurement of total hydrocarbons (THC) and non-methane hydrocarbons (NMHC) in stack gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsiao, H.H.; Lai, C.C.; Chu, H.W.

A new method for on-line monitoring of total hydrocarbons and non-methane hydrocarbons in stack gas simultaneously was developed in this study. Based on the principle of on-line GC/FID, the method was developed and can be considered as a new modification of the Method 25 and 25A of US EPA. Major advantages of the method included (1) capability of distinguishing methane as Method 25; (2) near-real-time results; (3) broad species coverage; (4) monitoring methane in straightforward manner; (5) low operation and maintenance costs. In the proposed method, test samples were continuously pumped from detection sources and loaded with a two-loop samplingmore » valve. The samples were then injected into two GC columns-empty and molecular sieve columns. The empty column was used for detection of THC, and the molecular sieve column was for methane. The detector in this GC was FID. NMHC concentration was obtained by subtracting methane from THC. The tests were carried out to measure the THC and methane in waste gas in various industries, including surface coating, semiconductor manufacturing, synthetic leather industries. Recovery rates of THC in the samples were between 86% to 114% for about 100 m of transfer line of samples. For the standard gas, the recovery rate was about 101%, 6.6 % of measurement precision, and 88%--114% of accuracy. The results showed the promising and reliable measurement of the test method for THC and methane in waste gas.« less

Colistin-resistant Escherichia coli clinical isolate harbouring the mcr-1 gene in Ecuador.

PubMed

Ortega-Paredes, D; Barba, P; Zurita, J

2016-10-01

Colistin resistance mediated by the mcr-1 gene has been reported worldwide, but to date not from the Andean region, South America. We report the first clinical isolate of Escherichia coli harbouring the mcr-1 gene in Ecuador. The strain was isolated from peritoneal fluid from a 14-year-old male with acute appendicitis, and subjected to molecular analysis. The minimum inhibitory concentration of colistin for the strain was 8 mg/ml and it was susceptible to carbapenems but resistant to tigecycline. The strain harboured mcr-1 and bla CTX-M-55 genes and was of sequence type 609. The recognition of an apparently commensal strain of E. coli harbouring mcr-1 serves as an alert to the presence in the region of this recently described resistance mechanism to one of the last line of drugs available for the treatment of multi-resistant Gram-negative infections.

75 FR 44235 - Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-28

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff Attendance at North American Electric Reliability Corporation Meetings July 21, 2010. The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and/or Commission staff may attend...

Pre-encoding administration of amphetamine or THC preferentially modulates emotional memory in humans

PubMed Central

Ballard, Michael E.; Gallo, David A.; de Wit, Harriet

2012-01-01

Rationale Many addictive drugs are known to have effects on learning and memory, and these effects could motivate future drug use. Specifically, addictive drugs may affect memory of emotional events and experiences in ways that are attractive to some users. However, few studies have investigated the effects of addictive drugs on emotional memory in humans. Objectives This study examined the effects of the memory-enhancing drug dextroamphetamine (AMP) and the memory-impairing drug Δ9-tetrahydrocannabinol (THC) on emotional memory in healthy volunteers. Methods Participants completed three experimental sessions across which they received capsules containing placebo and two doses of either AMP (10 and 20 mg; N=25) or THC (7.5 and 15 mg; N=25) before viewing pictures of positive (pleasant), neutral, and negative (unpleasant) scenes. Memory for the pictures was assessed two days later, under drug-free conditions. Results Relative to placebo, memory for emotional pictures was improved by AMP and impaired by THC, but neither drug significantly affected memory for unemotional pictures. Positive memory biases were not observed with either drug, and there was no indication that the drugs’ memory effects were directly related to their subjective or physiological effects alone. Conclusions This study provides the first clear evidence that stimulant drugs can preferentially strengthen, and cannabinoids can preferentially impair, memory for emotional events in humans. Although addictive drugs do not appear to positively bias memory, the possibility remains that these drugs’ effects on emotional memory could influence drug use among certain individuals. PMID:23224510

Detection and direction discrimination of single vortex rings by harbour seals (Phoca vitulina).

PubMed

Krüger, Yvonne; Hanke, Wolf; Miersch, Lars; Dehnhardt, Guido

2018-04-25

Harbour seals possess highly sensitive vibrissae that enable them to track hydrodynamic trails left behind by a swimming fish. Most of these trails contain vortex rings as a main hydrodynamic component. They may reveal information about their generator as the trails differ depending on the fish species, the fish's body shape, size and swimming style. In addition, fish generate single vortex rings in diverse natural situations. In this study, the ability of blindfolded stationary harbour seals to detect and analyse single vortex rings regarding directional information has been investigated. In three different behavioural experiments, the animals were trained to respond to single artificially generated vortex rings. The results show that harbour seals are able to respond to a variety of different vortex rings upon vibrissal stimulation. The investigation of the minimum hydrodynamically perceivable angle revealed that it is at least as small as 5.7 deg, which was the smallest adjustable angle. Moreover, harbour seals are capable of analysing the travel direction of a vortex ring perceived by the mystacial vibrissae irrespective of whether the vibrissae were stimulated ipsilaterally or contralaterally. In situations in which no complex hydrodynamic trail is available, it is advantageous for a hunting seal to be able to extract information from a single vortex ring. © 2018. Published by The Company of Biologists Ltd.

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

PubMed

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.

Geodetic infrastructure at the Barcelona harbour for sea level monitoring

NASA Astrophysics Data System (ADS)

Martinez-Benjamin, Juan Jose; Gili, Josep; Lopez, Rogelio; Tapia, Ana; Pros, Francesc; Palau, Vicenc; Perez, Begona

2015-04-01

The presentation is directed to the description of the actual geodetic infrastructure of Barcelona harbour with three tide gauges of different technologies for sea level determination and contribution to regional sea level rise and understanding past and present sea level rise in the Barcelona harbour. It is intended that the overall system will constitute a CGPS Station of the ESEAS (European Sea Level) and TIGA (GPS Tide Gauge Benchmark Monitoring) networks. At Barcelona harbour there is a MIROS radar tide gauge belonging to Puertos del Estado (Spanish Harbours).The radar sensor is over the water surface, on a L-shaped structure which elevates it a few meters above the quay shelf. 1-min data are transmitted to the ENAGAS Control Center by cable and then sent each 1 min to Puertos del Estado by e-mail. The information includes wave forescast (mean period, significant wave height, sea level, etc.This sensor also measures agitation and sends wave parameters each 20 min. There is a GPS station Leica Geosystems GRX1200 GG Pro and antenna AX 1202 GG. The Control Tower of the Port of Barcelona is situated in the North dike of the so-called Energy Pier in the Barcelona harbor (Spain). This tower has different kind of antennas for navigation monitoring and a GNSS permanent station. As the tower is founded in reclaimed land, and because its metallic structure, the 50 m building is subjected to diverse movements, including periodic fluctuations due to temperature changes. In this contribution the 2009, 2011, 2012, 2013 and 2014 the necessary monitoring campaigns are described. In the framework of a Spanish Space Project, the instrumentation of sea level measurements has been improved by providing the Barcelona site with a radar tide gauge Datamar 2000C from Geonica S.L. in June 2014 near an acoustic tide gauge from the Barcelona Harbour installed in 2013. Precision levelling has been made several times in the last two years because the tower is founded in reclaimed land and

17 CFR 200.43 - Disposition of business by exercise of authority delegated to individual Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Disposition of business by exercise of authority delegated to individual Commissioner. 200.43 Section 200.43 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION ORGANIZATION; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS...

STS-33 MS Carter operates translation hand control (THC) on aft flight deck

NASA Image and Video Library

1989-11-27

STS033-93-011 (27 Nov 1989) --- Astronaut Manley L. Carter, Jr., STS-33 mission specialist, operates translation hand control (THC) at the aft flight deck on orbit station while peering out overhead window W7. Carter's communications kit assembly headset microphone extends across his face.

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

PubMed

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.

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.

PubMed

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.

PubMed

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.

17 CFR 200.43 - Disposition of business by exercise of authority delegated to individual Commissioner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... exercise of authority delegated to individual Commissioner. 200.43 Section 200.43 Commodity and Securities... Disposition of Commission Business § 200.43 Disposition of business by exercise of authority delegated to... Commission; Provided, however, That no such delegation shall authorize the duty officer (i) to exercise the...

17 CFR 200.43 - Disposition of business by exercise of authority delegated to individual Commissioner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... exercise of authority delegated to individual Commissioner. 200.43 Section 200.43 Commodity and Securities... Disposition of Commission Business § 200.43 Disposition of business by exercise of authority delegated to... Commission; Provided, however, That no such delegation shall authorize the duty officer (i) to exercise the...

17 CFR 200.43 - Disposition of business by exercise of authority delegated to individual Commissioner.

Code of Federal Regulations, 2013 CFR

2013-04-01

... exercise of authority delegated to individual Commissioner. 200.43 Section 200.43 Commodity and Securities... Disposition of Commission Business § 200.43 Disposition of business by exercise of authority delegated to... Commission; Provided, however, That no such delegation shall authorize the duty officer (i) to exercise the...

17 CFR 200.43 - Disposition of business by exercise of authority delegated to individual Commissioner.

Code of Federal Regulations, 2011 CFR

2011-04-01

... exercise of authority delegated to individual Commissioner. 200.43 Section 200.43 Commodity and Securities... Disposition of Commission Business § 200.43 Disposition of business by exercise of authority delegated to... Commission; Provided, however, That no such delegation shall authorize the duty officer (i) to exercise the...

Chemical tracers of shipping emissions in a Mediterranean harbour

NASA Astrophysics Data System (ADS)

Viana, M.; Amato, F.; Alastuey, A.; Querol, X.; Román, A.; García, M.

2009-04-01

Particle emissions from transport-related activities are known as one of the most important sources contributing to the PM mass concentrations in urban environments. However, only limited information is currently available in the literature on the contribution to PM levels by specific transport related sources such as shipping emissions, even though according to the latest IPCC report (Ribeiro et al., 2007), shipping emissions are receiving increased scrutiny by international and regional regulatory agencies because of their potential impact on air quality and human health in communities downwind from major shipping lanes and ports (Dominguez et al., 2008). One of the main reasons for this lack of information is the complexity in the detection of shipping emissions, given that no specific emission tracers have so far been identified as a consequence of the vast variability of combustion fuels burnt by vessels. The city of Melilla was selected for the study of shipping emissions due to its location on the South-Western sector of the Mediterranean basin, on the Northern coast of Morocco and less than 200 km from the Gibraltar Strait (35°17´40" N, 2°56´30" W). The city covers an extension of 13.4 km2, with a population of 70000 inhabitants. The monitoring station selected for the present study is representative of urban background levels, and it is located at approximately 150 m from the Melilla harbour. The harbour is mainly characterised by commercial traffic (passanger and container), although minerals and other loose materials are also stocked on the docks located farthest away from the monitoring site. PM10, PM2.5 and PM1 levels were determined on an hourly basis between 12/01/2008 and 19/12/2008 using a GRIMM laser spectrometer, which produced more than 8000 data points for each size fraction (24000 data points in total). In addition, PM10 and PM2.5 levels were sampled on quartz fibre filter substrates (Munktell) by means of high-volume samplers (PM1025 MCV

17. MARINA WAY, HARBOUR WAY, AND MARITIME CHILD DEVELOPMENT CENTER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. MARINA WAY, HARBOUR WAY, AND MARITIME CHILD DEVELOPMENT CENTER (SEE ALSO HABS No. CA-2718), WITH RICHMOND SHIPYARD NO. 3. S. - Rosie the Riveter National Historical Park, 1401 Marina Way South, Richmond, Contra Costa County, CA

20 CFR 423.3 - Other process directed to the Social Security Administration or the Commissioner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Other process directed to the Social Security Administration or the Commissioner. 423.3 Section 423.3 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SERVICE OF PROCESS § 423.3 Other process directed to the Social Security Administration or the...

20 CFR 423.3 - Other process directed to the Social Security Administration or the Commissioner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Other process directed to the Social Security Administration or the Commissioner. 423.3 Section 423.3 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SERVICE OF PROCESS § 423.3 Other process directed to the Social Security Administration or the...

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

PubMed

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.

Ancient harbour infrastructure in the Levant: tracking the birth and rise of new forms of anthropogenic pressure.

PubMed

Marriner, Nick; Morhange, Christophe; Kaniewski, David; Carayon, Nicolas

2014-07-03

Beirut, Sidon and Tyre were major centres of maritime trade from the Bronze Age onwards. This economic prosperity generated increased pressures on the local environment, through urbanization and harbour development. Until now, however, the impact of expanding seaport infrastructure has largely been neglected and there is a paucity of data concerning the environmental stresses caused by these new forms of anthropogenic impacts. Sediment archives from Beirut, Sidon and Tyre are key to understanding human impacts in harbour areas because: (i) they lie at the heart of ancient trade networks; (ii) they encompass the emergence of early maritime infrastructure; and (iii) they enable human alterations of coastal areas to be characterized over long timescales. Here we report multivariate analyses of litho- and biostratigraphic data to probe human stressors in the context of their evolving seaport technologies. The statistical outcomes show a notable break between natural and artificial sedimentation that began during the Iron Age. Three anchorage phases can be distinguished: (i) Bronze Age proto-harbours that correspond to natural anchorages, with minor human impacts; (ii) semi-artificial Iron Age harbours, with stratigraphic evidence for artificial reinforcement of the natural endowments; and (iii) heavy human impacts leading to completely artificial Roman and Byzantine harbours.

Ancient harbour infrastructure in the Levant: tracking the birth and rise of new forms of anthropogenic pressure

PubMed Central

Marriner, Nick; Morhange, Christophe; Kaniewski, David; Carayon, Nicolas

2014-01-01

Beirut, Sidon and Tyre were major centres of maritime trade from the Bronze Age onwards. This economic prosperity generated increased pressures on the local environment, through urbanization and harbour development. Until now, however, the impact of expanding seaport infrastructure has largely been neglected and there is a paucity of data concerning the environmental stresses caused by these new forms of anthropogenic impacts. Sediment archives from Beirut, Sidon and Tyre are key to understanding human impacts in harbour areas because: (i) they lie at the heart of ancient trade networks; (ii) they encompass the emergence of early maritime infrastructure; and (iii) they enable human alterations of coastal areas to be characterized over long timescales. Here we report multivariate analyses of litho- and biostratigraphic data to probe human stressors in the context of their evolving seaport technologies. The statistical outcomes show a notable break between natural and artificial sedimentation that began during the Iron Age. Three anchorage phases can be distinguished: (i) Bronze Age proto-harbours that correspond to natural anchorages, with minor human impacts; (ii) semi-artificial Iron Age harbours, with stratigraphic evidence for artificial reinforcement of the natural endowments; and (iii) heavy human impacts leading to completely artificial Roman and Byzantine harbours. PMID:24989979

Ancient harbour infrastructure in the Levant: tracking the birth and rise of new forms of anthropogenic pressure

NASA Astrophysics Data System (ADS)

Marriner, Nick; Morhange, Christophe; Kaniewski, David; Carayon, Nicolas

2014-07-01

Beirut, Sidon and Tyre were major centres of maritime trade from the Bronze Age onwards. This economic prosperity generated increased pressures on the local environment, through urbanization and harbour development. Until now, however, the impact of expanding seaport infrastructure has largely been neglected and there is a paucity of data concerning the environmental stresses caused by these new forms of anthropogenic impacts. Sediment archives from Beirut, Sidon and Tyre are key to understanding human impacts in harbour areas because: (i) they lie at the heart of ancient trade networks; (ii) they encompass the emergence of early maritime infrastructure; and (iii) they enable human alterations of coastal areas to be characterized over long timescales. Here we report multivariate analyses of litho- and biostratigraphic data to probe human stressors in the context of their evolving seaport technologies. The statistical outcomes show a notable break between natural and artificial sedimentation that began during the Iron Age. Three anchorage phases can be distinguished: (i) Bronze Age proto-harbours that correspond to natural anchorages, with minor human impacts; (ii) semi-artificial Iron Age harbours, with stratigraphic evidence for artificial reinforcement of the natural endowments; and (iii) heavy human impacts leading to completely artificial Roman and Byzantine harbours.

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.

PubMed

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.

20 CFR 423.3 - Other process directed to the Social Security Administration or the Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICE OF PROCESS § 423.3 Other process directed to the Social Security Administration or the Commissioner. Subpoenas and other process (other than summonses and complaints) that are required to be served... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Other process directed to the Social Security...

Who benefits most from THC:CBD spray? Learning from clinical experience.

PubMed

Koehler, Jürgen

2014-01-01

Patients with multiple sclerosis (MS) represent a diverse and heterogeneous population varying in terms of disease type, its severity and variable progression/time-course, and with regard to the wide range of presenting symptoms. Consequently, detailed experience with individual patients is important to provide examples of therapy to specific patient types. In this article, real-life data from clinical practice showing specific aspects relating to use of 9-delta-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) in patients with moderate to severe spasticity resistant to usual therapy will be presented. Three common clinical scenarios will be considered: MS patients with resistance to usual spasticity therapies; patients with impairment in MS spasticity symptoms; MS patients with relevant impairment in quality of life/activities of daily living (QoL/ADL). These case reports highlight the diverse nature of the MS spasticity population and they show the possible usefulness of THC:CBD oromucosal spray in individual patients with moderate to severe spasticity resistant to existing therapies, within the frame of use approved after large clinical trial results. Perhaps the most important finding is the possibility of obtaining relevant improvements in QoL/ADL in some patients with resistant MS spasticity, allowing them to engage back in physical and social activities. © 2014 S. Karger AG, Basel.

77 FR 5791 - Notice of Commissioner and Staff Attendance at the National Association of Regulatory Utility...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioner and Staff... Commission and/or Commission staff may attend the following meetings: FERC/National Association of Regulatory... Service Commission of South Carolina and the South Carolina Office of Regulatory Staff Docket No. AD12-1...

Comparing Distribution of Harbour Porpoises (Phocoena phocoena) Derived from Satellite Telemetry and Passive Acoustic Monitoring

PubMed Central

Rigét, Frank F.; Kyhn, Line A.; Sveegaard, Signe; Dietz, Rune; Tougaard, Jakob; Carlström, Julia A. K.; Carlén, Ida; Koblitz, Jens C.; Teilmann, Jonas

2016-01-01

Cetacean monitoring is essential in determining the status of a population. Different monitoring methods should reflect the real trends in abundance and patterns in distribution, and results should therefore ideally be independent of the selected method. Here, we compare two independent methods of describing harbour porpoise (Phocoena phocoena) relative distribution pattern in the western Baltic Sea. Satellite locations from 13 tagged harbour porpoises were used to build a Maximum Entropy (MaxEnt) model of suitable habitats. The data set was subsampled to one location every second day, which were sufficient to make reliable models over the summer (Jun-Aug) and autumn (Sep-Nov) seasons. The modelled results were compared to harbour porpoise acoustic activity obtained from 36 static acoustic monitoring stations (C-PODs) covering the same area. The C-POD data was expressed as the percentage of porpoise positive days/hours (the number of days/hours per day with porpoise detections) by season. The MaxEnt model and C-POD data showed a significant linear relationship with a strong decline in porpoise occurrence from west to east. This study shows that two very different methods provide comparable information on relative distribution patterns of harbour porpoises even in a low density area. PMID:27463509

Patterns of Occurrence of Sharks in Sydney Harbour, a Large Urbanised Estuary.

PubMed

Smoothey, Amy F; Gray, Charles A; Kennelly, Steve J; Masens, Oliver J; Peddemors, Victor M; Robinson, Wayne A

2016-01-01

Information about spatial and temporal variability in the distribution and abundance of shark-populations are required for their conservation, management and to update measures designed to mitigate human-shark interactions. However, because some species of sharks are mobile, migratory and occur in relatively small numbers, estimating their patterns of distribution and abundance can be very difficult. In this study, we used a hierarchical sampling design to examine differences in the composition of species, size- and sex-structures of sharks sampled with bottom-set longlines in three different areas with increasing distance from the entrance of Sydney Harbour, a large urbanised estuary. During two years of sampling, we obtained data for four species of sharks (Port Jackson, Heterodontus portusjacksoni; wobbegong, Orectolobus maculatus; dusky whaler, Carcharhinus obscurus and bull shark, Carcharhinus leucas). Only a few O. maculatus and C. obscurus were caught, all in the area closest to the entrance of the Harbour. O. maculatus were caught in all seasons, except summer, while C. obscurus was only caught in summer. Heterodontus portusjacksoni were the most abundant species, caught in the entrance location mostly between July to November, when water temperature was below 21.5°C. This pattern was consistent across both years. C. leucas, the second most abundant species, were captured in all areas of Sydney Harbour but only in summer and autumn when water temperatures were above 23°C. This study quantified, for this first time, how different species utilise different areas of Sydney Harbour, at different times of the year. This information has implications for the management of human-shark interactions, by enabling creation of education programs to modify human behaviour in times of increased risk of potentially dangerous sharks.

Patterns of Occurrence of Sharks in Sydney Harbour, a Large Urbanised Estuary

PubMed Central

Smoothey, Amy F.; Gray, Charles A.; Kennelly, Steve J.; Masens, Oliver J.; Peddemors, Victor M.; Robinson, Wayne A.

2016-01-01

Information about spatial and temporal variability in the distribution and abundance of shark-populations are required for their conservation, management and to update measures designed to mitigate human-shark interactions. However, because some species of sharks are mobile, migratory and occur in relatively small numbers, estimating their patterns of distribution and abundance can be very difficult. In this study, we used a hierarchical sampling design to examine differences in the composition of species, size- and sex-structures of sharks sampled with bottom-set longlines in three different areas with increasing distance from the entrance of Sydney Harbour, a large urbanised estuary. During two years of sampling, we obtained data for four species of sharks (Port Jackson, Heterodontus portusjacksoni; wobbegong, Orectolobus maculatus; dusky whaler, Carcharhinus obscurus and bull shark, Carcharhinus leucas). Only a few O. maculatus and C. obscurus were caught, all in the area closest to the entrance of the Harbour. O. maculatus were caught in all seasons, except summer, while C. obscurus was only caught in summer. Heterodontus portusjacksoni were the most abundant species, caught in the entrance location mostly between July to November, when water temperature was below 21.5°C. This pattern was consistent across both years. C. leucas, the second most abundant species, were captured in all areas of Sydney Harbour but only in summer and autumn when water temperatures were above 23°C. This study quantified, for this first time, how different species utilise different areas of Sydney Harbour, at different times of the year. This information has implications for the management of human-shark interactions, by enabling creation of education programs to modify human behaviour in times of increased risk of potentially dangerous sharks. PMID:26824349

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

PubMed

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.

Selective habituation shapes acoustic predator recognition in harbour seals.

PubMed

Deecke, Volker B; Slater, Peter J B; Ford, John K B

2002-11-14

Predation is a major force in shaping the behaviour of animals, so that precise identification of predators will confer substantial selective advantages on animals that serve as food to others. Because experience with a predator can be lethal, early researchers studying birds suggested that predator recognition does not require learning. However, a predator image that can be modified by learning and experience will be advantageous in situations where cues associated with the predator are highly variable or change over time. In this study, we investigated the response of harbour seals (Phoca vitulina) to the underwater calls of different populations of killer whales (Orcinus orca). We found that the seals responded strongly to the calls of mammal-eating killer whales and unfamiliar fish-eating killer whales but not to the familiar calls of the local fish-eating population. This demonstrates that wild harbour seals are capable of complex acoustic discrimination and that they modify their predator image by selectively habituating to the calls of harmless killer whales. Fear in these animals is therefore focused on local threats by learning and experience.

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

NASA Astrophysics Data System (ADS)

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.

20 CFR 408.1060 - What happens if a Federal Court remands your case to the Commissioner?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What happens if a Federal Court remands your case to the Commissioner? 408.1060 Section 408.1060 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Determinations and the Administrative Review Process...

20 CFR 408.1060 - What happens if a Federal Court remands your case to the Commissioner?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What happens if a Federal Court remands your case to the Commissioner? 408.1060 Section 408.1060 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Determinations and the Administrative Review Process...

20 CFR 408.1060 - What happens if a Federal Court remands your case to the Commissioner?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What happens if a Federal Court remands your case to the Commissioner? 408.1060 Section 408.1060 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Determinations and the Administrative Review Process...

20 CFR 408.1060 - What happens if a Federal Court remands your case to the Commissioner?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What happens if a Federal Court remands your case to the Commissioner? 408.1060 Section 408.1060 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Determinations and the Administrative Review Process...

20 CFR 408.1060 - What happens if a Federal Court remands your case to the Commissioner?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false What happens if a Federal Court remands your case to the Commissioner? 408.1060 Section 408.1060 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Determinations and the Administrative Review Process...

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

PubMed

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.

Long-lasting alterations of hippocampal GABAergic neurotransmission in adult rats following perinatal Δ9-THC exposure.

PubMed

Beggiato, Sarah; Borelli, Andrea Celeste; Tomasini, Maria Cristina; Morgano, Lucia; Antonelli, Tiziana; Tanganelli, Sergio; Cuomo, Vincenzo; Ferraro, Luca

2017-03-01

The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored. To this purpose, pregnant rats were treated daily with Delta 9 -tetrahydrocannabinol (Δ 9 -THC; 5mg/kg) or its vehicle. Perinatal exposure to Δ 9 -THC induced a significant reduction (p<0.05) in basal and K + -evoked [ 3 H]-GABA outflow of 90-day-old rat hippocampal slices. These effects were associated with a reduction of hippocampal [ 3 H]-GABA uptake compared to vehicle exposed group. Perinatal exposure to Δ 9 -THC induced a significant reduction of CB1 receptor binding (B max ) in the hippocampus of 90-day-old rats. However, a pharmacological challenge with either Δ 9 -THC (0.1μM) or WIN55,212-2 (2μM), similarly reduced K + -evoked [ 3 H]-GABA outflow in both experimental groups. These reductions were significantly blocked by adding the selective CB1 receptor antagonist SR141716A. These findings suggest that maternal exposure to cannabinoids induces long-term alterations of hippocampal GABAergic system. Interestingly, previous behavioral studies demonstrated that, under the same experimental conditions as in the present study, perinatal cannabinoids exposure induced cognitive impairments in adult rats, thus resembling some effects observed in humans. Although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of hippocampus aminoacidergic transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring

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

PubMed

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

Recolonization of macrofauna in unpolluted sands placed in a polluted yachting harbour: A field approach using experimental trays

NASA Astrophysics Data System (ADS)

Guerra-García, J. M.; García-Gómez, J. C.

2009-01-01

A field experiment using trays was conducted at Ceuta's yachting harbour, North Africa, to study the effect in recolonization of placing trays with unpolluted defaunate sediments (fine and gross sands with low contents of organic matter) inside an enclosed yachting harbour characterized by high percentages of silt and clay and high concentrations of organic matter. Sediment recolonization in the trays was mainly undertaken by the species living naturally at the yachting harbour, which recolonized both uncontaminated gross and fine sand trays (such as the crustaceans Corophium runcicorne, Corophium sextonae and Nebalia bipes, the mollusc Parvicardium exiguum and the polychaete Pseudomalacoceros tridentata). However, other species like the polychaetes Cirriformia tentaculata and Platynereis dumerilii, although also abundant in the yachting harbour, were unable to colonize the trays through transport of larvae and/or adults in the water column. The recolonization was very quick, and after the first month, the values of abundance, species richness, diversity and evenness were similar in the experimental trays and in the reference area (yachting harbour). Although the multivariate analysis showed that the species composition differed between the trays and the reference area, there were no significant differences in recolonization of gross and fine sands, indicating that other factors different from the granulometry are modulating the recolonization patterns.

The ancient harbour system of Terracina (Latium, Italy) obtained by gravity survey.

NASA Astrophysics Data System (ADS)

di Nezza, M.; di Filippo, M.

2009-04-01

Historical research has shown that Terracina (Latina, Latium) played a fundamental role in the maritime and land traffic since before the foundation of the colony. The settlement was established where the organized system of maritime, land, coastal, and fluvial transport had the most ideal conditions to constitute an important commercial crossroads, apparently since the beginning of recorded history. In order to reconstruction the buried archaeological structures attributed to the ancient Roman port, traditionally attributed to Traiano, in the current area of the harbour of Terracina, it was carried out a gravity survey, more than 380 gravity stations. This method enables to recognize the cavity and the structures of the buildings underground through the results of variations density in the subsoil. In the residual gravity anomaly map a series of positive anomalies are visible which confirm the round structures and the pier of the buried foundations of the Imperial harbour. Unfortunately, little remains of the functioning facilities of the harbour's activities. The modern construction of the harbour, in fact, has to be developed around the new inhabitable commercial area, know today as Terracina Bassa or Borgo alla Marina. It had to be developed with a modern infrastructure of a harbor area, as in the construction of the rooms for storage of goods, warehouses, as well as for the thermal baths, hotels and amphitheatre. Furthermore, there are always the positive anomalies that characterize the area to the north-east of "Montone" hill where archaeological remains are easily visible near Via Lungolinea Pio VI. A large negative anomaly is situated in correspondence with "Montone". Gravity information shows an average density of the hill approximately 1.10 g/cm3, notably less than the recorded data relative to dry sand, approximately 1.6 g/cm3. The low value founds hits at the possibility of an "emptiness" in the subsoil of "Montone" hill, attribuiting to the possible

Early detection of potentially invasive invertebrate species in Mytilus galloprovincialis Lamarck, 1819 dominated communities in harbours

NASA Astrophysics Data System (ADS)

Preda, Cristina; Memedemin, Daniyar; Skolka, Marius; Cogălniceanu, Dan

2012-12-01

Constanţa harbour is a major port on the western coast of the semi-enclosed Black Sea. Its brackish waters and low species richness make it vulnerable to invasions. The intensive maritime traffic through Constanţa harbour facilitates the arrival of alien species. We investigated the species composition of the mussel beds on vertical artificial concrete substrate inside the harbour. We selected this habitat for study because it is frequently affected by fluctuating levels of temperature, salinity and dissolved oxygen, and by accidental pollution episodes. The shallow communities inhabiting it are thus unstable and often restructured, prone to accept alien species. Monthly samples were collected from three locations from the upper layer of hard artificial substrata (maximum depth 2 m) during two consecutive years. Ten alien macro-invertebrate species were inventoried, representing 13.5% of the total number of species. Two of these alien species were sampled starting the end of summer 2010, following a period of high temperatures that triggered hypoxia, causing mass mortalities of benthic organisms. Based on the species accumulation curve, we estimated that we have detected all benthic alien species on artificial substrate from Constanţa harbour, but additional effort is required to detect all the native species. Our results suggest that monitoring of benthic communities at small depths in harbours is a simple and useful tool in early detection of potentially invasive alien species. The selected habitat is easily accessible, the method is low-cost, and the samples represent reliable indicators of alien species establishment.

75 FR 7490 - Office of the Commissioner Reorganization; Statement of Organizations, Functions, and Delegations...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

...The Food and Drug Administration (FDA) is announcing the reorganization of the Office of the Commissioner (OC). This reorganization includes the organizations and their substructure components as listed in this document. This notice was previously published in the Federal Register of August 18, 2009, but it contained several errors. For the convenience of the reader, the reorganization is being published again in its entirety.

Assessing the importance of alien macro-Crustacea (Malacostraca) within macroinvertebrate assemblages in Belgian coastal harbours

NASA Astrophysics Data System (ADS)

Boets, Pieter; Lock, Koen; Goethals, Peter L. M.

2012-06-01

Harbours, which are often characterised by anthropogenic stress in combination with intensive international ship traffic, tend to be very susceptible to aquatic invasions. Since alien macrocrustaceans are known to be very successful across many European waters, a study was made on their distribution and impact in the four Belgian coastal harbours (Nieuwpoort, Ostend, Blankenberge and Zeebrugge). Biological and physical-chemical data were gathered at 43 sampling sites distributed along a salinity gradient in the four harbours. One-fourth of all crustacean species recorded were alien and represented on average 30% of the total macrocrustacean abundance and 65% of the total macrocrustacean biomass. The large share of alien crustaceans in the total macrocrustacean biomass was mainly due to several large alien crab species. Most alien species were found in the oligohaline zone, whereas the number of indigenous species slightly increased with increasing salinity. The low number of indigenous species present at low salinities was probably not only caused by salinity, but also by the lower water quality in this salinity range. Based on the site-specific biocontamination index (SBCI), which was used to assess the ecological water quality, the harbour of Nieuwpoort and Ostend scored best and were classified as good, indicating the limited abundance and the low number of alien macrocrustaceans. Sampling locations situated more inland generally had a higher SBCI and a lower ecological water quality. Zeebrugge and Blankenberge were characterised by a severe biocontamination. For Zeebrugge, this is probably related to the intensive transcontinental commercial ship traffic, whereas for Blankenberge, this could be due to introduction of alien species via recreational crafts or due to its geographical location in the proximity of Zeebrugge. Consistent monitoring of estuarine regions and harbours, which are seen as hotspots for introductions, could help in understanding and

Sustainable management of harbours : a numerical approach for the assessment of waters quality

NASA Astrophysics Data System (ADS)

Bonamano, Simone; Madonia, Alice; Piazzolla, Daniele; Paladini de Mendoza, Francesco; Piermattei, Viviana; Scanu, Sergio; Melchiorri, Cristiano; Marcelli, Marco

2017-04-01

Within the Water Framework Directive (WFD), harbours must reach or maintain the good ecological potential, being classified as heavily modified water bodies. To fulfill this task and to comply the Marine Spatial Planning (MSP) principles, port managers have to monitor the water quality that can be compromised by the numerous activities including the realization of new infrastructures. The port of Civitavecchia, located on the central west coast of Italy, is undergoing to major structural changes to become one of the first ports of the Mediterranean in terms of passenger traffic and goods, thus requiring the development of management tools for the predictive assessment of harbour water quality. This study focused on the evaluation of water degradation within Civitavecchia port trough the calculation of Flushing time (FT) and the development of the new Flushing Efficiency Index (FEI). FT was calculated through the use of a numerical model under different scenarios selected combining different weather conditions with the new port configurations. FT values was then used to estimate the FEI for the evaluation of the improvement (positive values) or the deterioration (negative values) of water quality in the different zones of the port. The increase in the harbour basin size due to the embankment extension results in high values of FT, particularly in the inner part of the port, in accordance with the highest values of the Enrichment Factor (EF) of the trace metals found in the sediment. The correlation between FT and EF confirms that renewal time can be used as a proxy to evaluate the water quality conditions in the harbour basin, as also stated by the WFD guidelines. Also the results of FEI calculation indicate the potential occurrence of water degradation due to the embankment extension. Otherwise, the realization of a second entrance in the southern part of Civitavecchia port produces FEI positive values, highlighting a drastic improvement in harbour water renewal

77 FR 1483 - Commissioners of Public Works of the City of Spartanburg, SC; Notice of Availability of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-10

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 4632-033] Commissioners of Public Works of the City of Spartanburg, SC; Notice of Availability of Environmental Assessment In accordance with the National Environmental Policy Act of 1969 and the Federal Energy Regulatory Commission's...

75 FR 71123 - Notice of Commissioners and Staff Attendance at FERC/NARUC Collaborative on Smart Response Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-22

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Commissioners and Staff Attendance at FERC/NARUC Collaborative on Smart Response Meeting November 12, 2010. The Federal Energy... Commission staff may attend the following meeting: FERC/NARUC Collaborative on Smart Response: Omni Hotel at...

Biodiversity loss in seagrass meadows due to local invertebrate fisheries and harbour activities

NASA Astrophysics Data System (ADS)

Nordlund, Lina Mtwana; Gullström, Martin

2013-12-01

Seagrass meadows provide a wide variety of ecosystem services, but their distribution and health are adversely affected by man. In the present study, we examined the influence of coastal exploitation in terms of invertebrate harvesting and harbour activity on invertebrate community composition in subtropical seagrass meadows at Inhaca Island, Mozambique, in the Western Indian Ocean. There was a fivefold higher invertebrate density and biomass, and clearly higher invertebrate species richness, in the protected (control) site compared to the two exploited sites. The causes for the clear differences between protected and exploited sites were probably a result of (1) the directional outtake of large edible or saleable invertebrates (mostly molluscs) and the absence of boat traffic in the harvested site, and (2) harbour activities. Invertebrate community composition in the two exploited sites also differed (although less clear), which was likely due to inherent distinction in type of disturbance. Our findings revealed that protection of seagrass habitat is necessary and that disturbances of different origin might require different forms of management and conservation. Designing protected areas is however a complex process due to competition for use and space with activities such as invertebrate harvesting and harbours.

Sediment transport modelling based on grain size trend analysis in Augusta Harbour (Sicily)

NASA Astrophysics Data System (ADS)

Barbera, Giuseppe; Feo, Roberto; Freni, Gabriele

2015-12-01

To support marine civil engineer in pollutant studies, sediment management or dredging operations, is useful to know how the sediments move in accumulation basin. This paper investigates the dynamic of the sediment path using a two-dimensional numeric model: the Grain Size Trend Analysis (GSTA). The GSTA was applied using GiSedTrend plugin, under GIS software. The case study is the Augusta Harbour, which is one of the most polluted Italian harbours. It is the marine part of the Site of National Interest (SNI) of Priolo Gargallo (Siracusa, Italy) and it can be hydrodynamically considered as a lagoon. Two scenarios were obtained by using different geostatistical criteria.

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

PubMed Central

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?

PubMed

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.

Delta-9-tetrahydrocannabinolic acid A (THC-A) in urine of a 15-month-old child: A case report.

PubMed

Morini, Luca; Quaiotti, Jessica; Moretti, Matteo; Osculati, Antonio Marco Maria; Tajana, Luca; Groppi, Angelo; Vignali, Claudia

2018-05-01

The acidic forms of cannabinoids, THC-A and CBD-A are naturally present in cannabis plants and preparations and are generally decarboxylated to the active compounds before the use (e.g. thermally decarboxylated through smoking). Hence, the identification of the acidic compounds in urine could be an evidence of cannabis ingestion rather than a passive exposure to smoke. This case report described a 15-month-old child that suffered an acute intoxication by accidental cannabis ingestion. It is important to assess the ingestion and to discriminate it from a passive exposure to better interpret the clinical findings and to establish the correct therapeutic procedure. Urine samples were simply diluted in deionized water and directly injected in the LC-MS/MS system. D 3 -THCCOOH was used as internal standard. Chromatographic separation of THCCOOH, THC-A and CBD-A was carried out in reversed phase on a c18 column. A triple quad in MRM negative mode was used to monitor the three analytes. The developed LC-MS/MS method was simple and fast. A LOD of 3.0ng/mL and a LOQ of 10.0ng/mL were measured for the three compounds. The analytical procedure was validated accordingly to international guidelines. The two urine samples collected from the 15-month-old child at the hospitalization and after three days provided positive results for THCCOOH (130.0 and 10.0ng/mL respectively). THC-A was found only in the urine sample collected at the hospitalization (concentration: 70.0ng/mL). THC-A was detected and quantitated in a urine sample of a 15-month-old child. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

75 FR 42747 - Smart Grid Update; Notice of Commissioner and Staff Attendance at FERC/NARUC Collaborative on...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-22

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD10-15-000] Smart Grid Update; Notice of Commissioner and Staff Attendance at FERC/NARUC Collaborative on Smart Response Meeting... Commission and/or Commission staff may attend the following meeting: FERC/NARUC Collaborative on Smart...

Heartworm (Acanthocheilonema spirocauda) and seal louse (Echinophthirius horridus) infections in harbour seals (Phoca vitulina) from the North and Baltic Seas

NASA Astrophysics Data System (ADS)

Lehnert, Kristina; Schwanke, Eva; Hahn, Kerstin; Wohlsein, Peter; Siebert, Ursula

2016-07-01

The seal louse (Echinophthirius [E.] horridus) and the heartworm (Acanthocheilonema [A.] spirocauda) are parasites of harbour seal (Phoca vitulina). Little is known about the role of the seal louse as a potential vector and its role for the development and transmission of heartworm larvae to their final host, the harbour seal. The life-cycle of the heartworm is still not fully understood. For the presented study, findings of 1191 stranded harbour seals collected along the North- and Baltic Sea coast between 1996 and 2013 were examined. 4.4% (n = 53) of these harbour seals were infected with adult heartworms and 3.4% (n = 40) harbour seals carried seal lice. The highest prevalence and level of infection with adult heartworms (A. spirocauda) (9.3%) and seal lice (E. horridus) (8.9%) were found on yearling harbour seals (7-18 months) compared to neonate and adult seals. Investigating seal lice (n = 35) for larval heartworm stages one larvae was encountered in an ethanol-fixated seal louse. During a health monitoring survey of live harbour seals, 109 animals were captured and examined during spring and autumn between 2008 and 2014. Blood samples were taken and microfilariae were discovered in blood smears in 41% (n = 45) of the examined harbour seals. Yearling seals (n = 21) showed higher prevalence (86%) and level of infection with microfilariae than adults. Microfilariae were identified as A. spirocauda by sequencing the species-specific COI gene in 24 blood samples. The high prevalence of microfilariae of A. spirocauda in blood samples (41%) is in contrast to the low prevalence of mature infections/adult specimens in stranded seals (4.4%) investigated. Although rare parasites of seals, the recent increase in prevalence of heartworm and seal lice in stranded seals and the relatively high occurrence of microfilaria in the free-ranging population underscore the importance of further studies investigating the immunology of infections and their transmission pathways, as

Mitochondrial DNA reveals secondary contact in Japanese harbour seals, the southernmost population in the western Pacific

PubMed Central

Sasaki, Takeshi; Kobayashi, Mari; Haneda, Takayuki; Masubuchi, Takahito

2018-01-01

In this study, we used relatively large number of samples (n = 178) and control region of mtDNA (454bp) to clearify the divergence history of Japanese harbour seals (Phoca vitulina stejnegeri) and phylogenetic relationship between the seals in Japan and other countries. Our results suggested that Japanese harbour seals possibly consisted of more than two lineages and secondary contact of populations after a long isolation. Furthermore, one of the lineage was made only by Japanese harbour seals (Group P1). The proportion of Group P1 was the highest at the South West and gradually decreased towards the North East of Hokkaido, Japan. On the other hand, the haplotypes do not belonged to Group P1 showed close relationship to the seals in the North Pacific. Based on the fossil record of harbour seal in Japan and the range of sea ice during the Last Glacial Maximum (LGM), Group P1 might have entered Japan before the LGM and became isolated due to the geographical boundary, and gradually extended its range from the South West towards the North East of Hokkaido after the disappearance of the sea ice, while the seals which are not in Group P1 immigrated into Japan from the North Pacific. PMID:29385193

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.

PubMed

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.

PubMed

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.

PubMed

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.

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

PubMed

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.

Mortality and histopathological effects in harbour-transplanted snails with different exposure histories.

PubMed

Bighiu, Maria Alexandra; Watermann, Burkard; Guo, Xueli; Almroth, Bethanie Carney; Eriksson-Wiklund, Ann-Kristin

2017-09-01

Contaminants are important stressors in the aquatic environment and may exert selective pressures on organisms. We hypothesized that snails originating from a metal-contaminated habitat (B) would have increased tolerance to harbour contaminants (e.g. metals from antifouling paints), compared to snails originating from a relatively clean habitat (A). We assessed tolerance to metals in terms of survival and histopathological alterations after 2, 4 and 8 weeks of in situ exposure in three Baltic Sea boat harbours and three reference sites. We also hypothesized that any potential tolerance to contaminants would be associated with differences in genetic diversity between the two snail populations (evaluated as mitochondrial cytochrome c oxidase subunit I, COI). The results show that snails from population A survived to a higher extent compared to population B, possibly indicating either a lack of adaptation to metals in snails B or impaired health condition due to contaminant pre-exposure or a higher resilience of snails A. Moreover, the genetic diversity of COI was low within each population and did not differ between populations. In general, 83% of all the types of histopathological alterations (e.g. lysis and necrosis of gonads and digestive gland or granulocytoma and phagocytosis in the storage tissue, among others) had a higher probability of occurrence among harbour-exposed snails compared to reference-exposed snails, regardless of snail population origin. The only significant difference in histological effects between the two populations was in the frequency of parasite infestations and shell fouling, both being larger for population A than B. Interestingly, the rate of parasite infestations was higher for males than females from population A, whereas no sexual dichotomy was observed for population B. Our results show that exposure to harbour contaminants causes both lethal and sublethal toxicity to snails, and the association between many of the toxic responses

Method of simultaneous stir bar sorptive extraction of phenethylamines and THC metabolite from urine.

PubMed

Goto, Yoshiyuki; Takeda, Shiho; Araki, Toshinori; Fuchigami, Takayuki

2011-10-01

Stir bar sorptive extraction is a technique used for extracting target substances from various aqueous matrixes such as environmental water, food, and biological samples. This type of extraction is carried out by rotating a coated stir bar is rotated in the sample solution. In particular, Twister bar is a commercial stir bar that is coated with polydimethylsiloxane (PDMS) and used to perform sorptive extraction. In this study, we developed a method for simultaneous detection of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and a Δ(9)-tetrahydrocannabiniol (THC) metabolite in human urine. For extracting the target analytes, the Twister bar was simply stirred in the sample in the presence of a derivatizing agent. Using this technique, phenethylamines and the acidic THC metabolite can be simultaneously extracted from human urine. This method also enables the extraction of trace amounts of these substances with good reproducibility and high selectivity. The proposed method offers many advantages over other extraction-based approaches and is therefore well suited for screening psychoactive substances in urine specimens.

45 CFR 1321.21 - Submission of the State plan or plan amendment to the Commissioner for approval.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Submission of the State plan or plan amendment to the Commissioner for approval. 1321.21 Section 1321.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE...

45 CFR 1321.21 - Submission of the State plan or plan amendment to the Commissioner for approval.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Submission of the State plan or plan amendment to the Commissioner for approval. 1321.21 Section 1321.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE...

45 CFR 1321.21 - Submission of the State plan or plan amendment to the Commissioner for approval.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Submission of the State plan or plan amendment to the Commissioner for approval. 1321.21 Section 1321.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE...

45 CFR 1321.21 - Submission of the State plan or plan amendment to the Commissioner for approval.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Submission of the State plan or plan amendment to the Commissioner for approval. 1321.21 Section 1321.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE...

45 CFR 1321.21 - Submission of the State plan or plan amendment to the Commissioner for approval.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Submission of the State plan or plan amendment to the Commissioner for approval. 1321.21 Section 1321.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE...

75 FR 51292 - Before Commissioners: Ruth Y. Goldway, Chairman; Tony L. Hammond, Vice Chairman; Mark Acton; Dan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-91; CP2010-92; CP2010-93; CP2010-94; Order No. 513] Before Commissioners: Ruth Y. Goldway, Chairman; Tony L. Hammond, Vice Chairman; Mark Acton; Dan G. Blair; and Nanci E. Langley; Competitive Product Prices; Global Expedited Package Services 3...

Implementation of CGPS at Estartit, Ibiza and Barcelona harbours for sea level monitoring

NASA Astrophysics Data System (ADS)

Martinez-Benjamin, J. J.; Ortiz Castellon, M.; Martinez-Garcia, M.; Perez, B.; Bosch, E.; Termens, A.; Martinez de Oses, X.

2009-12-01

The determination of global and regional mean sea level variations with accura-cies better than 1 mm/yr is a critical problem, the resolution of which is central to the current debate on climate change and its impact on the environment. Highly accurate time series from both satellite altimetry and tide gauges are needed. Measuring the sea surface height with in-situ tide gauges and GPS receivers pro-vides an efficient way to control the long term stability of the radar altimeters and other applications as the vertical land motion and studies of sea level change. L’Estartit tide gauge is a classical floating tide gauge set up in l’Estartit harbour (NE Spain) in 1990. Data are taken in graphics registers from which each two hours the mean value is recorded in an electronic support and delivered to the Permanent Service for Mean Sea level (PSMSL). Periodic surveying campaigns along the year are carried out for monitoring possible vertical movement of the geodetic benchmark adjacent to the tide gauge. Puertos del Estado (Spanish Harbours) installed the tide gauge station at Ibiza har-bour in January 2003 and a near GPS reference station. The station belongs to the REDMAR network, composed at this moment by 21 stations distributed along the whole Spanish waters, including also the Canary islands (http://www.puertos.es). The tide gauge also belongs to the ESEAS (European Sea Level) network. A description of the actual infrastructure at Ibiza, Barcelona and l’Estartit har-bours is presented.The main objective is the implementation of these harbours as a precise geodetic areas for sea level monitoring and altimeter calibration. Actually is a CGPS with a radar tide gauge from Puertos del Estado and a GPS belonging to Puerto de Barcelona. A precise levelling has been made by the Cartographic Insti-tute of Catalonia, ICC. The instrumentation of sea level measurements has been improved by providing the Barcelona site with a radar tide gauge Datamar 3000C device and a

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.

PubMed

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

Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans

PubMed Central

Klumpers, Floris; Denys, Damiaan; Kenemans, J Leon; Grillon, Christian; van der Aart, Jasper; Baas, Johanna MP

2012-01-01

Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB1 receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB1 or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-) clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB1 agonist. PMID:22351380

Health Authorities Data Collection of THC:CBD Oromucosal Spray (L'Agenzia Italiana del Farmaco Web Registry): Figures after 1.5 Years.

PubMed

Patti, Francesco

2016-01-01

In Italy, all prescriptions for THC:CBD oromucosal spray for treatment of multiple sclerosis (MS) spasticity are linked to the official Agenzia Italiana del Farmaco (AIFA) web-based registry, which tracks the effectiveness and tolerability of medications in a prospective and observational manner. AIFA e-registry data for THC:CBD oromucosal spray collected between January 2014 and February 2015 for 1,534 patients from 30 large Italian specialized MS centres were compiled. Patients had a long disease history (17.6 ± 8.6 years) and significant impairment (mean Expanded Disability Status Scale score 6.4 ± 1.2). MS spasticity was evaluated using the 0-10 numerical rating scale (NRS). After the first month titration and trial period, 61.9% of patients achieved sufficient improvement in spasticity (≥20% NRS) to qualify for continued treatment. After 6 months, clinically meaningful ≥30% NRS improvement was recorded in 40.2% of patients continuing with treatment. Spasticity-associated symptoms such as cramps and nocturnal spasms improved in most responding patients. Mean reported doses of THC:CBD oromucosal spray (6.2-6.7 sprays/day) were lower than those reported in clinical trials. Adverse events (mainly mild to moderate) were reported by 15% of patients; no new safety concerns beyond the approved label were identified. The results of the AIFA e-registry analysis align with those of other THC:CBD observational projects and reaffirm the characteristics of this therapeutic option in the management of treatment-resistant MS spasticity, a frequently overlooked symptom. © 2016 S. Karger AG, Basel.

A Method for Identifying Pollution Sources of Heavy Metals and PAH for a Risk-Based Management of a Mediterranean Harbour

PubMed Central

Moranda, Arianna

2017-01-01

A procedure for assessing harbour pollution by heavy metals and PAH and the possible sources of contamination is proposed. The procedure is based on a ratio-matching method applied to the results of principal component analysis (PCA), and it allows discrimination between point and nonpoint sources. The approach can be adopted when many sources of pollution can contribute in a very narrow coastal ecosystem, both internal and outside but close to the harbour, and was used to identify the possible point sources of contamination in a Mediterranean Harbour (Port of Vado, Savona, Italy). 235 sediment samples were collected in 81 sampling points during four monitoring campaigns and 28 chemicals were searched for within the collected samples. PCA of total samples allowed the assessment of 8 main possible point sources, while the refining ratio-matching identified 1 sampling point as a possible PAH source, 2 sampling points as Cd point sources, and 3 sampling points as C > 12 point sources. By a map analysis it was possible to assess two internal sources of pollution directly related to terminals activity. The study is the prosecution of a previous work aimed at assessing Savona-Vado Harbour pollution levels and suggested strategies to regulate the harbour activities. PMID:29270328

A Method for Identifying Pollution Sources of Heavy Metals and PAH for a Risk-Based Management of a Mediterranean Harbour.

PubMed

Paladino, Ombretta; Moranda, Arianna; Seyedsalehi, Mahdi

2017-01-01

A procedure for assessing harbour pollution by heavy metals and PAH and the possible sources of contamination is proposed. The procedure is based on a ratio-matching method applied to the results of principal component analysis (PCA), and it allows discrimination between point and nonpoint sources. The approach can be adopted when many sources of pollution can contribute in a very narrow coastal ecosystem, both internal and outside but close to the harbour, and was used to identify the possible point sources of contamination in a Mediterranean Harbour (Port of Vado, Savona, Italy). 235 sediment samples were collected in 81 sampling points during four monitoring campaigns and 28 chemicals were searched for within the collected samples. PCA of total samples allowed the assessment of 8 main possible point sources, while the refining ratio-matching identified 1 sampling point as a possible PAH source, 2 sampling points as Cd point sources, and 3 sampling points as C > 12 point sources. By a map analysis it was possible to assess two internal sources of pollution directly related to terminals activity. The study is the prosecution of a previous work aimed at assessing Savona-Vado Harbour pollution levels and suggested strategies to regulate the harbour activities.

Airborne emissions in the harbour and port of Cork.

PubMed

Sodeau, John R; Hellebust, Stig; Allanic, Arnaud; O'Connor, Ian; Healy, David A; Healy, Robert; Wenger, John

2009-07-01

It is now accepted that the transport sector is responsible for a large and growing share of global emissions affecting both health and climate. The quantification of these effects requires, as an essential first step, a comprehensive analysis and characterization of the contributing subsectors, i.e. road transport, shipping, aviation and rail. The shipping contribution in dock/harbour areas is of particular interest because many vessels use old engines powered with old technology giving rise to high levels of particulate emissions mainly because the fuel employed contains high levels of sulphur, up to 4.5%. Large amounts of polyaromatic hydrocarbons and varying contents of transition metals are also detected. Few studies on the physicochemical composition of direct emissions from ship fuels have been performed; none have been compared to actual contents in local harbour or port atmospheres. The transformation of these ship-related materials to toxicologically active species may be much more efficient than corresponding road emission or domestic sources because of the expected highly acidic nature of the particulates. Surface, toxic material may therefore become readily bioavailable under such conditions but such studies have not been performed hitherto. This mini-review outlines in detail the issues raised above in the context of measurements made in Cork, Ireland.

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

PubMed

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

Identification of a novel gammaherpesvirus associated with (muco)cutaneous lesions in harbour porpoises (Phocoena phocoena).

PubMed

van Beurden, Steven J; IJsseldijk, Lonneke L; Ordonez, Soledad R; Förster, Christine; de Vrieze, Geert; Gröne, Andrea; Verheije, M Hélène; Kik, Marja

2015-12-01

Herpesviruses infect a wide range of vertebrates, including toothed whales of the order Cetacea. One of the smallest toothed whales is the harbour porpoise (Phocoena phocoena), which is widespread in the coastal waters of the northern hemisphere, including the North Sea. Here, we describe the detection and phylogenetic analysis of a novel gammaherpesvirus associated with mucocutaneous and skin lesions in stranded harbour porpoises along the Dutch coast, tentatively designated phocoenid herpesvirus 1 (PhoHV1). Phylogenetically, PhoHV1 forms a monophyletic clade with all other gammaherpesviruses described in toothed whales (Odontoceti) to date, suggesting a common evolutionary origin.

Even High Doses of Oral Cannabidol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102-112; DOI: 10.1089/can.2015.0004.

PubMed

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that "the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response." They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses.

Removal of Historic Low-Level Radioactive Sediment from the Port Hope Harbour - 13314

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolberg, Mark; Case, Glenn; Ferguson Jones, Andrea

2013-07-01

At the Port Hope Harbour, located on the north shore of Lake Ontario, the presence of low-level radioactive sediment, resulting from a former radium and uranium refinery that operated alongside the Harbour, currently limits redevelopment and revitalization opportunities. These waste materials contain radium-226, uranium, arsenic and other contaminants. Several other on-land locations within the community of Port Hope are also affected by the low-level radioactive waste management practices of the past. The Port Hope Project is a community initiated undertaking that will result in the consolidation of an estimated 1.2 million cubic metres of the low-level radioactive waste from themore » various sites in Port Hope into a new engineered above ground long-term waste management facility. The remediation of the estimated 120,000 m{sup 3} of contaminated sediments from the Port Hope Harbour is one of the more challenging components of the Port Hope Project. Following a thorough review of various options, the proposed method of contaminated sediment removal is by dredging. The sediment from the dredge will then be pumped as a sediment-water slurry mixture into geo-synthetic containment tubes for dewatering. Due to the hard substrate below the contaminated sediment, the challenge has been to set performance standards in terms of low residual surface concentrations that are attainable in an operationally efficient manner. (authors)« less

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.

PubMed

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

A comparison of eutrophication impacts in two harbours in Hong Kong with different hydrodynamics

NASA Astrophysics Data System (ADS)

Xu, J.; Yin, K.; Liu, H.; Lee, J. H. W.; Anderson, D. M.; Ho, A. Y. T.; Harrison, P. J.

2010-11-01

Eutrophication impacts may vary spatially and temporally due to different physical processes. Using a 22-year time series data set (1986-2007), a comparison was made of eutrophication impacts between the two harbours with very different hydrodynamic conditions. Victoria Harbour (Victoria) receives sewage effluent and therefore nutrients are abundant. In the highly-flushed Victoria, the highest monthly average Chl a (13 μg L -1) occurred during the period of strongest stratification in summer as a result of rainfall, runoff and the input of the nutrient-rich Pearl River estuarine waters, but the high flushing rate restricted nutrient utilization and further accumulation of algal biomass. In other seasons, vertical mixing induced light limitation and horizontal dilution led to low Chl a (< 2 μg L -1) and no spring bloom. Few hypoxic events (DO < 2 mg L -1) occurred due to re-aeration and limited accumulation at depth due to flushing and vertical mixing. Therefore, Victoria is resilient to nutrient enrichment. In contrast, in the weakly-flushed Tolo Harbour (Tolo), year long stratification, long residence times and weak tidal currents favored algal growth, resulting in a spring diatom bloom and high Chl a (10-30 μg L -1) all year and frequent hypoxic events in summer. Hence, Tolo is susceptible to nutrient enrichment and responded to nutrient reduction after sewage diversion in 1997. Sewage diversion from Tolo resulted in a 32-38% decrease in algal biomass in Tolo, but not in Victoria. There has been a significant increase (11-22%) in bottom DO in both harbours. Our findings demonstrate that an understanding of the role of physical processes is critical in order to predict the effectiveness of sewage management strategies in reducing eutrophication impacts.

Pathology of finfish and mud crabs Scylla serrata during a mortality event associated with a harbour development project in Port Curtis, Australia.

PubMed

Dennis, M M; Diggles, B K; Faulder, R; Olyott, L; Pyecroft, S B; Gilbert, G E; Landos, M

2016-10-27

The objective of this study was to assess the extent and describe the nature of a multi-species marine finfish and crustacean disease event that occurred in Gladstone Harbour, Australia, 2011-2012. Finfish were examined for this study in January to April 2012 from sites where diseased animals were previously observed by the public. Gross abnormalities, including excessive skin and gill mucus, erythema, heavy ecto-parasitism, cutaneous ulceration, corneal opacity, and exophthalmos, were higher (25.5%) in finfish from Gladstone Harbour (n = 435) than in those from an undeveloped reference site, 250 km to the north (5.5%, n = 146, p < 0.0001). Microscopic abnormalities, especially non-infectious erosive to ulcerative dermatitis and internal parasitism, were more prevalent in fish from Gladstone Harbour (n = 34 of 36, prevalence = 94.4%) than in fish from the reference site (3 of 23, prevalence = 13.0% p < 0.0001). The prevalence of shell lesions was higher in mud crabs Scylla serrata sampled from Gladstone Harbour (270 of 718, prevalence = 37.5%) than from the reference site (21 of 153, prevalence = 13.7%; p < 0.0001). The significantly higher prevalence of ulcerative skin disease and parasitism in a range of species suggests affected animals were subjected to influences in Gladstone Harbour that were not present in the control sites. The disease epidemic coincided temporally and spatially with water quality changes caused by a harbour development project. The unique hydrology, geology, and industrial history of the harbour, the scope of the development of the project, and the failure of a bund wall built to retain dredge spoil sediment were important factors contributing to this epidemic.

Geodetic Infrastructure in the Ibiza and Barcelona Harbours for Sea Level Monitoring

NASA Astrophysics Data System (ADS)

Martinez-Benjamin, J. J.; Gili, J.; Lopez, R.; Tapia, A.; Perez, B.; Pros, F.

2013-12-01

The presentation is directed to the description of the actual situation and relevant information of the geodetic infrastructure of Ibiza and Barcelona sites for sea level determination and contribution to regional sea level rise. Time series are being analysed for mean sea level variations www.puertos.es. .In the framework of a Spanish Space Project, the instrumentation of sea level measurements has been improved by providing the Barcelona site with a radar tide gauge Datamar 2000C from Geonica s.l. near an acoustic tide gauge. Puertos del Estado installed in 2007 a MIROS radar tide gauge and the Barcelona Harbour Authority a GPS referente station in the roof of the new Control Tower situated in the Energy Pier. The radar sensor is over the water surface, on a L-shaped structure which elevates it a few meters above the quay shelf. 1-min data are transmitted to the ENAGAS Control Center by cable and then sent each 1 min to Puertos del Estado by e-mail. There is a GPS station Leica Geosystems GRX1200 GG Pro and antenna 1202. Precision levelling has been made several times in the last two years because the tower is founded in reclaimed land. The measured settlement rate is about 1cm/year that may be could mask the values registered by the tide gauge. A description of the actual infrastructure at Ibiza harbour at Marina de Botafoch, is presented and its applications to sea level monitoring and altimeter calibration in support of the main CGPS at Ibiza harbour. It is described the geometrical precision levelling made in June 2013 between the radar tide gauge and the GPS station. In particular, the CGPS located at Ibiza harbour is essential for its application to the marine campaign Baleares 2013, near Ibiza island. The main objective is to determine the altimeter bias for Jason-2, about 9:09 UTC September 15, 2013, and Saral/AltiKa, about 05:30 UTC September 16, UTC. These activities has been received funding of the Ministerio de Ciencia e Innovacion under Spanish

20 CFR 403.130 - What factors may the Commissioner consider in determining whether SSA will grant your application...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What factors may the Commissioner consider in determining whether SSA will grant your application for testimony? 403.130 Section 403.130 Employees' Benefits SOCIAL SECURITY ADMINISTRATION TESTIMONY BY EMPLOYEES AND THE PRODUCTION OF RECORDS AND INFORMATION IN...

Charting the Development of Portsmouth Harbour, Dockyard and Town in the Tudor Period

NASA Astrophysics Data System (ADS)

Fontana, Dominic

2013-12-01

Portsmouth was crucial to the defence of Tudor England and consequently it was mapped for military planning purposes throughout the Tudor period from 1545. The resulting sequence of maps records much of the town and harbour. The maps offer opportunities for furthering our understanding of Tudor Portsmouth and its population Additionally, images of the urban landscape provided by the "Cowdray Engraving", which depicts the loss of Henry VIII's warship Mary Rose on the 19th July 1545, may also be considered and compared with those presented in the early maps of the town. This paper considers the Portsmouth maps of 1545, 1552, 1584 and the chart of Portsmouth Harbour dating from between 1586 and 1620. These are examined in relation to one another and compared with evidence from the Cowdray Engraving.

A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.

PubMed

Langford, R M; Mares, J; Novotna, A; Vachova, M; Novakova, I; Notcutt, W; Ratcliffe, S

2013-04-01

Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically

Even High Doses of Oral Cannabidiol Do Not Cause THC-Like Effects in Humans: Comment on Merrick et al. Cannabis and Cannabinoid Research 2016;1(1):102–112; DOI: 10.1089/can.2015.0004

PubMed Central

Grotenhermen, Franjo; Russo, Ethan; Zuardi, Antonio Waldo

2017-01-01

Abstract This short communication examines the question whether the experimental data presented in a study by Merrick et al. are of clinical relevance. These authors found that cannabidiol (CBD), a major cannabinoid of the cannabis plant devoid of psychotropic effects and of great interest for therapeutic use in several medical conditions, may be converted in gastric fluid into the psychoactive cannabinoids delta-8-THC and delta-9-THC to a relevant degree. They concluded that “the acidic environment during normal gastrointestinal transit can expose orally CBD-treated patients to levels of THC and other psychoactive cannabinoids that may exceed the threshold for a positive physiological response.” They issued a warning concerning oral use of CBD and recommend the development of other delivery methods. However, the available clinical data do not support this conclusion and recommendation, since even high doses of oral CBD do not cause psychological, psychomotor, cognitive, or physical effects that are characteristic for THC or cannabis rich in THC. On the contrary, in the past decades and by several groups, high doses of oral CBD were consistently shown to cause opposite effects to those of THC in clinical studies. In addition, administration of CBD did not result in detectable THC blood concentrations. Thus, there is no reason to avoid oral use of CBD, which has been demonstrated to be a safe means of administration of CBD, even at very high doses. PMID:28861499

Views of commissioners, managers and healthcare professionals on the NHS Health Check programme: a systematic review.

PubMed

Mills, Katie; Harte, Emma; Martin, Adam; MacLure, Calum; Griffin, Simon J; Mant, Jonathan; Meads, Catherine; Saunders, Catherine L; Walter, Fiona M; Usher-Smith, Juliet A

2017-11-15

To synthesise data concerning the views of commissioners, managers and healthcare professionals towards the National Health Service (NHS) Health Check programme in general and the challenges faced when implementing it in practice. A systematic review of surveys and interview studies with a descriptive analysis of quantitative data and thematic synthesis of qualitative data. An electronic literature search of MEDLINE, Embase, Health Management Information Consortium, Cumulative Index of Nursing and Allied Health Literature, Global Health, PsycInfo, Web of Science, OpenGrey, the Cochrane Library, NHS Evidence, Google Scholar, Google, ClinicalTrials.gov and the International Standard Randomised Controlled Trial Number registry from 1 January 1996 to 9 November 2016 with no language restriction and manual screening of reference lists of all included papers. Primary research reporting views of commissioners, managers or healthcare professionals on the NHS Health Check programme and its implementation in practice. Of 18 524 citations, 15 articles met the inclusion criteria. There was evidence from both quantitative and qualitative studies that some commissioners and general practice (GP) healthcare professionals were enthusiastic about the programme, whereas others raised concerns around inequality of uptake, the evidence base and cost-effectiveness. In contrast, those working in pharmacies were all positive about programme benefits, citing opportunities for their business and staff. The main challenges to implementation were: difficulties with information technology and computer software, resistance to the programme from some GPs, the impact on workload and staffing, funding and training needs. Inadequate privacy was also a challenge in pharmacy and community settings, along with difficulty recruiting people eligible for Health Checks and poor public access to some venues. The success of the NHS Health Check Programme relies on engagement by those responsible for its

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

PubMed

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.

Palatability and oral cavity tolerability of THC:CBD oromucosal spray and possible improvement measures in multiple sclerosis patients with resistant spasticity: a pilot study.

PubMed

Lus, Giacomo; Cantello, Roberto; Danni, Maura Chiara; Rini, Agusto; Sarchielli, Paola; Tassinari, Tiziana; Signoriello, Elisabetta

2018-04-01

Complaints about Δ 9 -tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex ® ; GW Pharma Ltd, Salisbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies. This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects. Patients with multiple sclerosis spasticity (n = 52) at six sites in Italy who were receiving THC:CBD oromucosal spray and had associated oral mucosal effects were randomized into Group A (chewing gum; n = 15); Group B (cold bottle; n = 20); and Group C (cold bottle + chewing gum; n = 17). Taste perception in patients receiving chewing gum ± cold bottle intervention (Groups A and C combined) was significantly (p = 0.0001) improved from baseline to week 4 while maintaining spasticity control. Patient comfort, satisfaction and treatment adherence may benefit from these interventions.

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

PubMed Central

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

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

PubMed

Russo, Ethan B

2011-08-01

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. http

The Development and Characteristics of Ancient Harbours-Applying the PADM Chart to the Case Studies of Ostia and Portus.

PubMed

Salomon, Ferreol; Keay, Simon; Carayon, Nicolas; Goiran, Jean-Philippe

2016-01-01

Over the last 20 years, the geoarchaeology of ancient harbours has been a very active area of research around the Mediterranean basin, generating much palaeoenvironmental data from many sites, including estimations of sedimentation rates, the height of the ancient sea-level at different dates and palaeo-geographical reconstructions. Combining this information has proved a major challenge. This article proposes a new chart called the Palaeoenvironmental Age-Depth Model (PADM chart), that allows the researchers to combine all relevant indicators in order to estimate harbour potential of a given ancient port, and to generate comparable data between harbours in terms of degree of closure and water depth available against a synchronised chronology. This new approach, developed in the context of the ERC-funded RoMP Portuslimen project, takes into account estimations of water depths relating to differing Roman ship draughts at different periods. It is tested against the palaeoenvironmental evidence published over 10 years from two Roman harbours located at the mouth of the river Tiber: Ostia and Portus. This reveals that: (1) there has been an underestimate of the real sedimentation rates due to the margins of error of the radiocarbon dates; (2) there was effective control of the water column by dredging; (3) there were different periods of control of the sedimentation. We suggest that the navigability of the Ostia harbour by ships with shallower draughts was maintained until sometime between the 2nd c. BC and 1st c. AD, while at Portus it was retained until the 6th-7th c. AD.

Identification of potential fish carcinogens in sediment from Hamilton Harbour, Ontario, Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balch, G.C.; Metcalfe, C.D.; Huestis, S.Y.

1995-01-01

A carcinogenicity- and mutagenicity-directed fractionation approach was used to identify the carcinogenic compounds in contaminated sediments that are putatively responsible for the high prevalence of tumors in bottom-dwelling fish from Hamilton Harbour, Ontario. Mutagenic activity was detected with Ames tester strains (TA98, TA100) in relatively nonpolar fractions of sediment extract containing PAHs and nitrogen-containing aromatic compounds (NCACs). These fractions were also carcinogenic in an in vivo carcinogenicity bioassay with rainbow trout (Oncorhynchus mykiss). When a more polar extract fraction was tested for mutagenicity and carcinogenicity, weak mutagenic activity was detected with an O-acetyltransferase-enriched Ames tester strain (YG1024), and weak carcinogenicmore » activity was detected in the rainbow trout assay. These data indicate that PAHs in contaminated Hamilton Harbour sediments are potent fish carcinogens, but it is also evident that other organic compounds in the sediment, such as NCACs and nitroarenes, may contribute to carcinogenicity.« less

Seal dynamics on the Swedish west coast: Scenarios of competition as Baltic grey seal intrude on harbour seal territory

NASA Astrophysics Data System (ADS)

Svensson, Carl Johan

2012-07-01

The Kattegat-Skagerrak region on the Swedish west coast is home to an abundant harbour seal population (Phoca vitulina) and a small scattered grey seal population (Halichoerus grypus). In addition, grey seal from the growing population in the Baltic Sea frequently migrate into the Kattegat-Skagerrak. Harbour seals on the west coast of Sweden show relatively high population growth (approximately 9%) compared to the Baltic grey seal in ice-free habitats (approximately 6%), which, in theory, makes harbour seal the stronger competitor of the two in this region. However, incidents of disease in harbour seals that lower population growth are becoming more frequent. These epidemics are primarily caused by the Phocine Distemper Virus (PDV), and may reduce population size with up to 70%. This study models the average development under potential scenarios of competing harbour- and Baltic grey seal populations using Leslie matrices and the Lotka-Volterra model of inter-specific competition. The model is parameterised with previously published data, and resource overlap is incorporated through density dependent pup survival. Using numerical methods short- and long-term abundances are simulated under weak, moderate and strong competition and for different frequencies of PDV epidemics. Results show that the harbour seals are resilient to competition while exerting a negative effect on grey seal abundance under moderate to strong competition. Hence Baltic grey seal benefit from weaker levels of competition. Under moderate and strong competition grey seal abundance is a direct function of the PDV frequency as this reduces the competitive strength of harbour seals. Theoretically this means that higher frequencies of PDV or other pathogens epidemics could facilitate an expansion of Baltic grey seal into Kattegat-Skagerrak. Independent of interaction strength and frequency of epidemics the projected changes to abundances are slow (50-100 years), and even in exceedingly stable

20 CFR 403.140 - If the Commissioner authorizes testimony, what will be the scope and form of that testimony?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If the Commissioner authorizes testimony, what will be the scope and form of that testimony? 403.140 Section 403.140 Employees' Benefits SOCIAL SECURITY ADMINISTRATION TESTIMONY BY EMPLOYEES AND THE PRODUCTION OF RECORDS AND INFORMATION IN LEGAL...

Monitoring Sea Level by Tide Gauges and GPS at Barcelona and Estartit Harbours

NASA Astrophysics Data System (ADS)

Martinez Benjamin, J. J.; Gili, J.; Lopez, R.; Tapia, A.; Bosch, E.; Perez, B.; Pros, F.

2012-04-01

Sea level is an environmental variable which is widely recognised as being important in many scientific disciplines as a control parameter for coastal dynamical processes or climate processes in the coupled atmosphere-ocean systems, as well as engineering applications. A major source of sea-level data are the national networks of coastal tide gauges, in Spain belonging to different institutions as the Instituto Geográfico Nacional (IGN), Puertos del Estado (PE), Instituto Hidrográfico de la Marina (IHM), etc. The tide gauge of l'Estartit is a traditional floating gauge placed 21 years ago and has an accuracy of ± 2 mm. Since 1996, l'Estartit tide gauge has been co-located with geodetic techniques (GPS measurements of XU, Utilitary Network, and XdA, Levelling Network,) and it is tied to the SPGIC (Integrated Geodetic Positioning System of Catalonia) project of the Cartographic Institute of Catalunya (ICC). In 2006, due to the work for the expansion of the harbour, the tide gauge had to be moved. Before the work started, appropiate GPS measurements were carried out in order to ensure the connection of the tide gauge data. During October 2006 and May 2008, the tide gauge was inactive and it has been moved on to a new location inside the harbour. In June 2008, new GPS and levelling measures have been done in order to tie the new location into SPGIC project and to co-locate old data respect the new one. Although l'Estartit does not have a GPS permanent station, it is possible to build a virtual one from the service "CATNET web" of the ICC. "CATNET web" is a data distribution system of a virtual GPS permanent station via web. From the coordinates where you want to place the virtual station, the time interval and the measurement rate, the system generates a RINEX file under the requested conditions. At Barcelona harbour there is one MIROS radar tide gauge belonging to Puertos del Estado (Spanish Harbours). It is placed at the dock 140 of the ENAGAS Building.The radar

Applicability of market-based instruments for safeguarding water quality in coastal waterways: Case study for Darwin Harbour, Australia

NASA Astrophysics Data System (ADS)

Greiner, Romy

2014-02-01

Water pollution of coastal waterways is a complex problem due to the cocktail of pollutants and multiplicity of polluters involved and pollution characteristics. Pollution control therefore requires a combination of policy instruments. This paper examines the applicability of market-based instruments to achieve effective and efficient water quality management in Darwin Harbour, Northern Territory, Australia. Potential applicability of instruments is examined in the context of biophysical and economic pollution characteristics, and experience with instruments elsewhere. The paper concludes that there is potential for inclusion of market-based instruments as part of an instrument mix to safeguard water quality in Darwin Harbour. It recommends, in particular, expanding the existing licencing system to include quantitative pollution limits for all significant point polluters; comprehensive and independent pollution monitoring across Darwin Harbour; public disclosure of water quality and emissions data; positive incentives for landholders in the Darwin Harbour catchment to improve land management practices; a stormwater offset program for greenfield urban developments; adoption of performance bonds for developments and operations which pose a substantial risk to water quality, including port expansion and dredging; and detailed consideration of a bubble licensing scheme for nutrient pollution. The paper offers an analytical framework for policy makers and resource managers tasked with water quality management in coastal waterways elsewhere in Australia and globally, and helps to scan for MBIs suitable in any given environmental management situation.

Contribution of harbour activities to atmospheric aerosol in the Brindisi area

NASA Astrophysics Data System (ADS)

Donateo, Antonio; Cesari, Daniela; Nocioni, Alessandra; Grasso, Fabio M.; Merico, Eva; Giua, Roberto; Contini, Daniele

2013-04-01

The port areas are economic centres and transport hubs, that bring together different transport modes (sea, road, railway transport) and also industrial activities. Ship emissions when docked and during port manoeuvring can have a substantial negative effect on local air quality. The Fagerli and Tarrason (2001) simulation results indicated that ship traffic emissions contribute to 5% and 10% of PM10 concentrations in large parts of Great Britain, Portugal and Italy; similarly to what was obtained by Dalsoren et al. (2009). At the beginning of 2012 it was started the research project CESAPO (Contribution of Emission Sources on the Air quality of the POrt-cities in Greece and Italy), funded within the framework of Interreg Italy-Greece (2007/2013), having as objective the quantification of the contribution to atmospheric particles of emission sources in two important Mediterranean port-cities, namely Patra (Greece) and Brindisi (Italy). In this work the first results of the CESAPO project will be presented giving more emphasis on the analysis of the maritime transport and the activities within the harbour of Brindisi that is characterized by several emission sources operating concurrently. In 2010 and 2011, in the port of Brindisi freight traffic and total goods movement accounted for more than 9.5 million tons, with over 520,000 passengers. To recognize the contribution of harbour activities to PM2.5 and to the total number concentration of particles with respect to other emission sources (urban traffic and industrial pollution) it has been performed an intensive observation period (IOP) of 5 months (June 1 to October 31, 2012). During the IOP the data of 10 fixed monitoring stations (of the regional network managed by ARPA Puglia) and those from two additional stations specifically installed during the project inside the harbour area. A station was used to characterize the chemical composition of PM2.5 and PAHs (in the gaseous and aerosol phases) and the other was

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the sub-chronic PCP model of schizophrenia

PubMed Central

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

2017-01-01

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 CSF 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 to 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. PMID:26510449

Community School Board Elections in New York City. A Report to the New York State Commissioner of Education.

ERIC Educational Resources Information Center

Rubin, Max J.

Following reports of irregularities in the May 1973 school board elections of New York City, the New York Commissioner of Education asked the author to identify the difficulties encountered by the voters and candidates, on both election day and in the period for registration and nomination which preceded it, and to recommend such changes in the…

20 CFR 403.140 - If the Commissioner authorizes testimony, what will be the scope and form of that testimony?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., what will be the scope and form of that testimony? 403.140 Section 403.140 Employees' Benefits SOCIAL... PROCEEDINGS § 403.140 If the Commissioner authorizes testimony, what will be the scope and form of that testimony? The employee's testimony must be limited to matters that were specifically approved. We will...

Decision making of heavy cannabis users on the Iowa Gambling Task: stronger association with THC of hair analysis than with personality traits of the Tridimensional Personality Questionnaire.

PubMed

Hermann, Derik; Leménager, Tagrid; Gelbke, Jan; Welzel, Helga; Skopp, Gisela; Mann, Karl

2009-01-01

It is unclear whether impairment in decision making, measured by the Iowa Gambling Task (IGT), in addiction is substance-induced or the consequence of personality structure. Analysis of the IGT, the Tridimensional Personality Questionnaire (TPQ) and cannabinoids in hair and urine were performed in 13 cannabis users and matched controls. Hair Delta(9)-tetrahydrocannabinol (THC) correlated negatively with the last subtrial (cards 80-100) of the IGT (R = -0.67). In all participants (n = 26) the TPQ dimension, harm avoidance, correlated negatively with the total IGT score (R = -0.46). The last IGT-subtrial correlated with adventure seeking (R = 0.43), harm avoidance (R = -0.39) and reward dependence (R = -0.44). The last subtrial gives information on whether a participant has learned the IGT strategy. Multiple regression confirmed the impact of THC on the last subtrial, whereas TPQ personality traits did not additionally explain variance. Former indications of the IGT performance depending on the amount of cannabis consumed were replicated with an objective measurement of chronic cannabis consumption (hair THC). Multiple regression analysis argues for a stronger impact of chronic THC consumption than personality traits, but does not provide a causal relationship. Other factors (e.g. genetic) may also play a role. 2009 S. Karger AG, Basel.

Modelling changes in the coastal geomorphology of Unst, Shetland and the implications for understanding High to Late Medieval harbour changes in the Norse North Atlantic

NASA Astrophysics Data System (ADS)

Preston, John; Dugmore, Andrew; Newton, Anthony; Mudd, Simon

2016-04-01

The Norse settlement of the North Atlantic islands relied upon a network of harbours that also played a key role in the development of North European economies through the late Middle Ages. However, many of these harbours fell into disuse, their locations are uncertain and the reasons for this are unclear. A crucial geomorphological characteristic of a successful harbour is structural equilibrium. A harbour must have physical stability (or a dynamic equilibrium in the case of a beach) for boats to use it safely season to season, year on year. In the absence of a major civil engineering effort, something that was not possible in the pre-modern Atlantic islands, the geomorphology of a harbour is a key indicator of its physical equilibrium (or otherwise). Should the harbour be located on a changeable coastline (or one that becomes changeable) it may become unviable. Conversely, a harbour may be located on a coastline stable over centennial timescales, where little geomorphological change occurs, infrastructure can endure and many aspects of the physical environment remain predictable. The geomorphological setting of Norse harbours in the Atlantic is variable, with contrasting landform stability over short, medium and long time scales. We assess geomorphological change on the island of Unst, the most northerly of the British Isles, a coastline used by the Norse as well as earlier and later societies. This island offers a complex coastline of deep fjords and arcuate embayments and thus significant differences in forces acting upon the coastline. There is also evidence for instability in the beaches used by the Norse that could have been driven by the changes in climate conditions from the Medieval Climatic Anomaly to the Little Age and the present day. We model coastlines using the sediment dynamics model MIKE21. Model results agree well with the location of extant sandy beaches on Unst, but model runs with modern environmental drivers also build sandy beaches where

Endoparasitic helminths of the harbour seal, Phoca vitulina, in the Netherlands

NASA Astrophysics Data System (ADS)

Borgsteede, F. H. M.; Bus, H. G. J.; Verplanke, J. A. W.; van Burg, W. P. J.

The endoparasitic helminth fauna of harbour seals which had died during the epidemic of the phocine distemper virus in 1988 was studied. Lungs, heart and gastrointestinal tracts of 94 animals collected along the Dutch coast were available for investigation. The following parasites and infection percentages were found: Nematoda: Dipetalonema spirocauda (24.5%), Otostrongylus circumlitus (6.4%), Parafilaroides gymnurus (24.5%), Ascaridoidea spec. (58.5%); Trematoda: Phagicola septentrionalis (66.0%), Cryptocotyle lingua (74.5%); Cestoda: Diphyllobothrium spec. (8.5%); Acanthocephala: Corynosoma strumosum (70.2%). The presence of worm species was not evenly distributed over the age classes. Seals younger than one year harboured fewer parasites. The highest percentages were found in 1 to 2 year old seals. The number of worms per seal varied greatly. The highest burden for ascarids was 253, for P. septentrionalis 123 000, for C. lingua 112 000 and for C. strumosum 251. A comparison of the present results with those described in the literature shows that in Dutch seals the same species were present and that numbers of worms were not higher than before the 1988 mass mortality. It is therefore concluded that helminth parasites did not cause the mass mortality.

[Asbestos import in Italy: the transit through Livorno harbour from 1957 to 1995].

PubMed

Nemo, Alessandro; Boccuzzi, Maria Teresa; Silvestri, Stefano

2009-01-01

This work aims to describe quantities, type of packaging and geographical area of origin of the asbestos fibres unloaded in Livorno harbour between 1957 and 1995. Historical data, available for this period, were collected from Il Messaggero Marittimo, a periodical journal dealing with Livorno harbour activities. Collaboration between the local Health and Safety Unit (ASL 6) and the Institute for Study and Prevention of Cancer (ISPO), both Regional Institutions of the National Health Service, made it possible to carry out this work. The computation of the collected data for the whole period allows the description of the quantities, year by year and the assessment of the percentage imported through Livorno on the total tonnage imported in Italy during the same period. The detection of the geographical areas of origin allowed to estimate the quantities subdivided by type of fibre (serpentine/amphiboles). These results will help the historical assessment of occupational asbestos exposure of the Livorno dockers.

Environmental impacts of iron ore tailings—The case of Tolo Harbour, Hong Kong

NASA Astrophysics Data System (ADS)

Wong, M. H.

1981-03-01

Disposal of iron ore tailings along the shore of Tolo Harbour, Hong Kong has altered the adjacent environment. Due to the ever-expanding population, the vast development of various industries, and the lack of sanitary control, the existing pollution problem of Tolo Harbour is serious. The iron ore tailings consist of a moderate amount of various heavy metals, e.g., copper, iron, manganese, lead, zinc, and a lower level of macronutrients. A few living organisms have been found colonizing this manmade habitat. Higher metal contents were also found in the tissue of Paphia sp. (clam); Scopimera intermedia (crab); Chaetomorpha brychagona (green alga); Enteromorpha crinita (green alga); and Neyraudia reynaudiana (grass). The area can be reclaimed by surface amelioration using inert materials, soils, or organic substrates, and by direct seeding, using nontolerant and tolerant plant materials. Reclamation of the tailings would improve the amenity of the adjacent environment and also mitigate pollution escaping to the sea.

Wave simulation for the design of an innovative quay wall: the case of Vlorë Harbour

NASA Astrophysics Data System (ADS)

Antonini, Alessandro; Archetti, Renata; Lamberti, Alberto

2017-01-01

Sea states and environmental conditions are basic data for the design of marine structures. Hindcasted wave data have been applied here with the aim of identifying the proper design conditions for an innovative quay wall concept. In this paper, the results of a computational fluid dynamics model are used to optimise the new absorbing quay wall of Vlorë Harbour (Republic of Albania) and define the design loads under extreme wave conditions. The design wave states at the harbour entrance have been estimated analysing 31 years of hindcasted wave data simulated through the application of WaveWatch III. Due to the particular geography and topography of the Bay of Vlorë, wave conditions generated from the north-west are transferred to the harbour entrance with the application of a 2-D spectral wave module, whereas southern wave states, which are also the most critical for the port structures, are defined by means of a wave generation model, according to the available wind measurements. Finally, the identified extreme events have been used, through the NewWave approach, as boundary conditions for the numerical analysis of the interaction between the quay wall and the extreme events. The results show that the proposed method, based on numerical modelling at different scales from macro to meso and to micro, allows for the identification of the best site-specific solutions, also for a location devoid of any wave measurement. In this light, the objectives of the paper are two-fold. First, they show the application of sea condition estimations through the use of wave hindcasted data in order to properly define the design wave conditions for a new harbour structure. Second, they present a new approach for investigating an innovative absorbing quay wall based on CFD modelling and the NewWave theory.

The harbour of Elaia: A palynological archive for human environmental interactions during the last 7500 years

NASA Astrophysics Data System (ADS)

Shumilovskikh, Lyudmila S.; Seeliger, Martin; Feuser, Stefan; Novenko, Elena; Schlütz, Frank; Pint, Anna; Pirson, Felix; Brückner, Helmut

2016-10-01

Elaia, the harbour city for ancient Pergamon (western Turkey), was investigated using geoarchaeological methods. The rise and fall of Elaia were closely linked to the flourishing period of Pergamon, which ruled wide parts of today's western Turkey in Hellenistic times. In the framework of this research, the palynological analysis of a 9 m sediment core, Ela-70, retrieved from the enclosed harbour of the city, was carried out to reconstruct the vegetation and environmental history of the wider Gulf of Elaia region. An age-depth model, based on 11 calibrated radiocarbon ages, starting from 7.5 ka BP, provides the basis for the high resolution study of sediments from the Hellenistic period, as well as before and after. The lower part of the pollen diagram is characterised by high percentages of deciduous oaks and pines, suggesting the dominance of open forests close to the coring site. The change from oak forests to a cultural landscape, with olive, pistachio, walnut, and grape, started around 850 BC, reaching a maximum ca. 250 BC, and continuing to ca. AD 800. This period is characterised by increase of fire activity, soil erosion intensity, and pastoral farming. Such long-lasting intensive land use likely led to the climax ecosystem turnover from open deciduous oak forests to pine stands, while salt marshes developed around the coring site. The discovery of the dinoflagellate cysts of Peridinium ponticum, a Black Sea endemic species, in the harbour of Elaia evidences maritime trade between the Aegean Sea and the Black Sea; its first occurrence coincides with the time of the Mithridatic Wars (1st century BC). In conclusion, palynological data, in addition to historical and archaeological records, provide a deeper insight into human environmental interactions, as derived from the geoarchaeological archive of the harbour of Elaia.

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

PubMed

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 < 0.01) and tar deposition significantly less (p < 0.03) for 3.95% than 1.77% MJ. Although individual adaptations in smoking topography for 3.95% compared to 1.77% MJ were highly variable, three subjects with the lowest 3.95% MJ:1.77% MJ ratios for CPV also displayed the lowest 3.95% MJ:1.77% MJ ratios for tar deposition. In vitro studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p < 0.05), but no difference between 1.77% and 0% 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.

Hydrodynamic sensory threshold in harbour seals (Phoca vitulina) for artificial flatfish breathing currents.

PubMed

Niesterok, Benedikt; Dehnhardt, Guido; Hanke, Wolf

2017-07-01

Harbour seals have the ability to detect benthic fish such as flatfish using the water currents these fish emit through their gills (breathing currents). We investigated the sensory threshold in harbour seals for this specific hydrodynamic stimulus under conditions which are realistic for seals hunting in the wild. We used an experimental platform where an artificial breathing current was emitted through one of eight different nozzles. Two seals were trained to search for the active nozzle. Each experimental session consisted of eight test trials of a particular stimulus intensity and 16 supra-threshold trials of high stimulus intensity. Test trials were conducted with the animals blindfolded. To determine the threshold, a series of breathing currents differing in intensity was used. For each intensity, three sessions were run. The threshold in terms of maximum water velocity within the breathing current was 4.2 cm s -1 for one seal and 3.7 cm s -1 for the other. We measured background flow velocities from 1.8 to 3.4 cm s -1 Typical swimming speeds for both animals were around 0.5 m s -1 Swimming speed differed between successful and unsuccessful trials. It appears that swimming speed is restricted for the successful detection of a breathing current close to the threshold. Our study is the first to assess a sensory threshold of the vibrissal system for a moving harbour seal under near-natural conditions. Furthermore, this threshold was defined for a natural type of stimulus differing from classical dipole stimuli which have been widely used in threshold determination so far. © 2017. Published by The Company of Biologists Ltd.

Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring

PubMed Central

Szutorisz, Henrietta; Egervari, Gabor; Sperry, James; Carter, Jenna M.; Hurd, Yasmin L.

2016-01-01

Cannabis (Cannabis sativa, Cannabis indica) is the illicit drug most frequently abused by young men and women. The growing use of the drug has raised attention not only on the impact of direct exposure on the developing brain and behavior later in life, but also on potential cross-generational consequences. Our previous work demonstrated that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, affects reward-related behavior and striatal gene expression in male offspring that were unexposed to the drug during their own lifespan. The significant sex differences documented for most addiction and psychiatric disorders suggest that understanding the perturbation of the brain in the two sexes due to cannabis could provide insights about neuronal systems underpinning vulnerability to psychiatric illnesses. In the current study, we expanded our previous observations in males by analyzing the female brain for specific aberrations associated with cross-generational THC exposure. Based on the impact of adolescent development on subsequent adult behavioral pathology, we examined molecular patterns during both adolescence and adulthood. The results revealed a switch from the ventral striatum during adolescence to the dorsal striatum in adulthood in alterations of gene expression related to synaptic plasticity in both sexes. Females, however, exhibited stronger correlation patterns between genes and also showed locomotor disturbances not evident in males. Overall, the findings demonstrate cross-generational consequences of parental THC exposure in both male and female offspring. PMID:27221226

The Canadian Human Rights Commission and Issues of Concern for Aboriginal Women. Notes for Remarks, by the Deputy Chief Commissioner.

ERIC Educational Resources Information Center

Falardeau-Ramsay, Michelle

This speech by the deputy chief commissioner of the Canadian Human Rights Commission discusses human rights, employment security, and pay-equity issues for Native Canadian women. The speech, offered in both English and French, calls the inequality of opportunity for Native Canadians a "national tragedy." It describes efforts to bring…

Do syntopic host species harbour similar symbiotic communities? The case of Chaetopterus spp. (Annelida: Chaetopteridae).

PubMed

Britayev, Temir A; Mekhova, Elena; Deart, Yury; Martin, Daniel

2017-01-01

To assess whether closely related host species harbour similar symbiotic communities, we studied two polychaetes, Chaetopterus sp. ( n  = 11) and Chaetopterus cf. appendiculatus ( n  = 83) living in soft sediments of Nhatrang Bay (South China Sea, Vietnam). The former harboured the porcellanid crabs Polyonyx cf. heok and Polyonyx sp., the pinnotherid crab Tetrias sp. and the tergipedid nudibranch Phestilla sp. The latter harboured the polynoid polychaete Ophthalmonoe pettiboneae , the carapid fish Onuxodon fowleri and the porcellanid crab Eulenaios cometes , all of which, except O. fowleri , seemed to be specialized symbionts. The species richness and mean intensity of the symbionts were higher in Chaetopterus sp. than in C. cf. appendiculatus (1.8 and 1.02 species and 3.0 and 1.05 individuals per host respectively). We suggest that the lower density of Chaetopterus sp. may explain the higher number of associated symbionts observed, as well as the 100% prevalence (69.5% in C. cf. appenciculatus ). Most Chaetopterus sp. harboured two symbiotic species, which was extremely rare in C. cf. appendiculatus , suggesting lower interspecific interactions in the former. The crab and nudibranch symbionts of Chaetopterus sp. often shared a host and lived in pairs, thus partitioning resources. This led to the species coexisting in the tubes of Chaetopterus sp., establishing a tightly packed community, indicating high species richness and mean intensity, together with a low species dominance. In contrast, the aggressive, strictly territorial species associated with C. cf. appendiculatus established a symbiotic community strongly dominated by single species and, thus, low species richness and mean intensity. Therefore, we suggest that interspecific interactions are determining species richness, intensity and dominance, while intraspecific interactions are influencing only intensity and abundance. It is possible that species composition may have influenced the differences in

Do syntopic host species harbour similar symbiotic communities? The case of Chaetopterus spp. (Annelida: Chaetopteridae)

PubMed Central

Britayev, Temir A.; Mekhova, Elena; Deart, Yury

2017-01-01

To assess whether closely related host species harbour similar symbiotic communities, we studied two polychaetes, Chaetopterus sp. (n = 11) and Chaetopterus cf. appendiculatus (n = 83) living in soft sediments of Nhatrang Bay (South China Sea, Vietnam). The former harboured the porcellanid crabs Polyonyx cf. heok and Polyonyx sp., the pinnotherid crab Tetrias sp. and the tergipedid nudibranch Phestilla sp. The latter harboured the polynoid polychaete Ophthalmonoe pettiboneae, the carapid fish Onuxodon fowleri and the porcellanid crab Eulenaios cometes, all of which, except O. fowleri, seemed to be specialized symbionts. The species richness and mean intensity of the symbionts were higher in Chaetopterus sp. than in C. cf. appendiculatus (1.8 and 1.02 species and 3.0 and 1.05 individuals per host respectively). We suggest that the lower density of Chaetopterus sp. may explain the higher number of associated symbionts observed, as well as the 100% prevalence (69.5% in C. cf. appenciculatus). Most Chaetopterus sp. harboured two symbiotic species, which was extremely rare in C. cf. appendiculatus, suggesting lower interspecific interactions in the former. The crab and nudibranch symbionts of Chaetopterus sp. often shared a host and lived in pairs, thus partitioning resources. This led to the species coexisting in the tubes of Chaetopterus sp., establishing a tightly packed community, indicating high species richness and mean intensity, together with a low species dominance. In contrast, the aggressive, strictly territorial species associated with C. cf. appendiculatus established a symbiotic community strongly dominated by single species and, thus, low species richness and mean intensity. Therefore, we suggest that interspecific interactions are determining species richness, intensity and dominance, while intraspecific interactions are influencing only intensity and abundance. It is possible that species composition may have influenced the differences in community

Echoes from the past: Regional variations in recovery within a harbour seal population

PubMed Central

Reijnders, Peter J. H.; Cremer, Jenny; Meesters, Erik; Kirkwood, Roger; Jensen, Lasse Fast; Jeβ, Armin; Galatius, Anders; Teilmann, Jonas; Aarts, Geert

2018-01-01

Terrestrial and marine wildlife populations have been severely reduced by hunting, fishing and habitat destruction, especially in the last centuries. Although management regulations have led to the recovery of some populations, the underlying processes are not always well understood. This study uses a 40-year time series of counts of harbour seals (Phoca vitulina) in the Wadden Sea to study these processes, and demonstrates the influence of historical regional differences in management regimes on the recovery of this population. While the Wadden Sea is considered one ecologically coupled zone, with a distinct harbour seal population, the area is divided into four geo-political regions i.e. the Netherlands, Lower Saxony including Hamburg, Schleswig-Holstein and Denmark. Gradually, seal hunting was banned between 1962 and 1977 in the different regions. Counts of moulting harbour seals and pup counts, obtained during aerial surveys between 1974 and 2014, show a population growth from approximately 4500 to 39,000 individuals. Population growth models were developed to assess if population growth differed between regions, taking into account two Phocine Distemper Virus (PDV) epizootics, in 1988 and 2002 which seriously affected the population. After a slow start prior to the first epizootic, the overall population grew exponentially at rates close to assumed maximum rates of increase in a harbour seal population. Recently, growth slowed down, potentially indicative of approaching carrying capacity. Regional differences in growth rates were demonstrated, with the highest recovery in Netherlands after the first PDV epizootic (i.e. 17.9%), suggesting that growth was fuelled by migration from the other regions, where growth remained at or below the intrinsic growth rate (13%). The seals’ distribution changed, and although the proportion of seals counted in the German regions declined, they remained by far the most important pupping region, with approximately 70% of all

Echoes from the past: Regional variations in recovery within a harbour seal population.

PubMed

Brasseur, Sophie M J M; Reijnders, Peter J H; Cremer, Jenny; Meesters, Erik; Kirkwood, Roger; Jensen, Lasse Fast; Jeβ, Armin; Galatius, Anders; Teilmann, Jonas; Aarts, Geert

2018-01-01

Terrestrial and marine wildlife populations have been severely reduced by hunting, fishing and habitat destruction, especially in the last centuries. Although management regulations have led to the recovery of some populations, the underlying processes are not always well understood. This study uses a 40-year time series of counts of harbour seals (Phoca vitulina) in the Wadden Sea to study these processes, and demonstrates the influence of historical regional differences in management regimes on the recovery of this population. While the Wadden Sea is considered one ecologically coupled zone, with a distinct harbour seal population, the area is divided into four geo-political regions i.e. the Netherlands, Lower Saxony including Hamburg, Schleswig-Holstein and Denmark. Gradually, seal hunting was banned between 1962 and 1977 in the different regions. Counts of moulting harbour seals and pup counts, obtained during aerial surveys between 1974 and 2014, show a population growth from approximately 4500 to 39,000 individuals. Population growth models were developed to assess if population growth differed between regions, taking into account two Phocine Distemper Virus (PDV) epizootics, in 1988 and 2002 which seriously affected the population. After a slow start prior to the first epizootic, the overall population grew exponentially at rates close to assumed maximum rates of increase in a harbour seal population. Recently, growth slowed down, potentially indicative of approaching carrying capacity. Regional differences in growth rates were demonstrated, with the highest recovery in Netherlands after the first PDV epizootic (i.e. 17.9%), suggesting that growth was fuelled by migration from the other regions, where growth remained at or below the intrinsic growth rate (13%). The seals' distribution changed, and although the proportion of seals counted in the German regions declined, they remained by far the most important pupping region, with approximately 70% of all pups

Hepatic CYP1A levels and EROD activity in English sole: biomonitoring of marine contaminants in Vancouver Harbour.

PubMed

Miller, K A; Addison, R F; Bandiera, S M

2004-01-01

To assess chemical contaminant stress in the marine environment, ethoxyresorufin-O-deethylase (EROD) activity and cytochrome P450 1A (CYP1A) expression were measured in 88 English Sole (Pleuronectes vetulus) collected during May and June 1999 from four sites in Vancouver Harbour and at an expected reference site outside the harbour. Hepatic microsomes were prepared from the fish and analyzed for total CYP content, EROD activity, and CYP1A protein levels. Hepatic EROD activity and CYP1A protein levels were elevated in fish from two sites in the inner harbour. A comparison with sediment chemistry data showed that fish with increased EROD activity and CYP1A levels came from sites containing relatively high levels of polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Unexpectedly high levels of EROD activity and CYP1A protein were also found in fish from a reference site near Gibsons, in Howe Sound. The elevated EROD activity and CYP1A expression in fish from this site cannot be explained by the chemical analysis data collected.

An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray

PubMed Central

Etges, Tilden; Karolia, Kari; Grint, Thomas; Taylor, Adam; Lauder, Heather; Daka, Brian; Wright, Stephen

2016-01-01

The global exposure of Sativex® (Δ9-tetrahydrocannabinol [THC]:cannabidiol [CBD], nabiximols) is estimated to be above 45,000 patient-years since it was given marketing approval for treating treatment-resistant spasticity in multiple sclerosis (MS). An observational registry to collect safety data from patients receiving THC:CBD was set up following its approval in the UK, Germany, and Switzerland, with the aim of determining its long-term safety in clinical practice. Twice a year, the Registry was opened to prescribing physicians to voluntarily report data on patients’ use of THC:CBD, clinically significant adverse events (AEs), and special interest events. The Registry contains data from 941 patients with 2,213.98 patient-years of exposure. Within this cohort, 60% were reported as continuing treatment, while 83% were reported as benefiting from the treatment. Thirty-two percent of patients stopped treatment, with approximately one third citing lack of effectiveness and one quarter citing AEs. Psychiatric AEs of clinical significance were reported in 6% of the patients, 6% reported falls requiring medical attention, and suicidality was reported in 2%. Driving ability was reported to have worsened in 2% of patients, but improved in 7%. AEs were more common during the first month of treatment. The most common treatment-related AEs included dizziness (2.3%) and fatigue (1.7%). There were no signals to indicate abuse, diversion, or dependence. The long-term risk profile from the Registry is consistent with the known (labeled) safety profile of THC:CBD, and therefore supports it being a well-tolerated and beneficial medication for the treatment of MS spasticity. No evidence of new long-term safety concerns has emerged. PMID:27956834

An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex® (THC:CBD, nabiximols) oromucosal spray.

PubMed

Etges, Tilden; Karolia, Kari; Grint, Thomas; Taylor, Adam; Lauder, Heather; Daka, Brian; Wright, Stephen

2016-01-01

The global exposure of Sativex ® (Δ 9 -tetrahydrocannabinol [THC]:cannabidiol [CBD], nabiximols) is estimated to be above 45,000 patient-years since it was given marketing approval for treating treatment-resistant spasticity in multiple sclerosis (MS). An observational registry to collect safety data from patients receiving THC:CBD was set up following its approval in the UK, Germany, and Switzerland, with the aim of determining its long-term safety in clinical practice. Twice a year, the Registry was opened to prescribing physicians to voluntarily report data on patients' use of THC:CBD, clinically significant adverse events (AEs), and special interest events. The Registry contains data from 941 patients with 2,213.98 patient-years of exposure. Within this cohort, 60% were reported as continuing treatment, while 83% were reported as benefiting from the treatment. Thirty-two percent of patients stopped treatment, with approximately one third citing lack of effectiveness and one quarter citing AEs. Psychiatric AEs of clinical significance were reported in 6% of the patients, 6% reported falls requiring medical attention, and suicidality was reported in 2%. Driving ability was reported to have worsened in 2% of patients, but improved in 7%. AEs were more common during the first month of treatment. The most common treatment-related AEs included dizziness (2.3%) and fatigue (1.7%). There were no signals to indicate abuse, diversion, or dependence. The long-term risk profile from the Registry is consistent with the known (labeled) safety profile of THC:CBD, and therefore supports it being a well-tolerated and beneficial medication for the treatment of MS spasticity. No evidence of new long-term safety concerns has emerged.

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

PubMed

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.

Serratia marcescens harbouring SME-type class A carbapenemases in Canada and the presence of blaSME on a novel genomic island, SmarGI1-1.

PubMed

Mataseje, L F; Boyd, D A; Delport, J; Hoang, L; Imperial, M; Lefebvre, B; Kuhn, M; Van Caeseele, P; Willey, B M; Mulvey, M R

2014-07-01

An increasing prevalence since 2010 of Serratia marcescens harbouring the Ambler class A carbapenemase SME prompted us to further characterize these isolates. Isolates harbouring bla(SME) were identified by PCR and sequencing. Phenotypic analysis for carbapenemase activity was carried out by a modified Hodge test and a modified Carba NP test. Antimicrobial susceptibilities were determined by Etest and Vitek 2. Typing was by PFGE of macrorestriction digests. Whole-genome sequencing of three isolates was carried out to characterize the genomic region harbouring the bla(SME)-type genes. All S. marcescens harbouring SME-type enzymes could be detected using a modified Carba NP test. Isolates harbouring bla(SME) were resistant to penicillins and carbapenems, but remained susceptible to third-generation cephalosporins, as well as fluoroquinolones and trimethoprim/sulfamethoxazole. Isolates exhibited diverse genetic backgrounds, though 57% of isolates were found in three clusters. Analysis of whole-genome sequence data from three isolates revealed that the bla(SME) gene occurred in a novel cryptic prophage genomic island, SmarGI1-1. There has been an increasing occurrence of S. marcescens harbouring bla(SME) in Canada since 2010. The bla(SME) gene was found on a genomic island, SmarGI1-1, that can be excised and circularized, which probably contributes to its dissemination amongst S. marcescens. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Characterization of contaminants in snapping turtles (Chelydra serpentina) from Canadian Lake Erie Areas of Concern: St. Clair River, Detroit River, and Wheatley Harbour.

PubMed

de Solla, Shane R; Fernie, Kimberly J

2004-11-01

PCBs, organochlorine pesticides and dioxins/furans in snapping turtle eggs and plasma (Chelydra serpentina) were evaluated at three Areas of Concern (AOCs) on Lake Erie and its connecting channels (St. Clair River, Detroit River, and Wheatley Harbour), as well as two inland reference sites (Algonquin Provincial Park and Tiny Marsh) in 2001-2002. Eggs from the Detroit River and Wheatley Harbour AOCs had the highest levels of p,p'-DDE (24.4 and 57.9 ng/g) and sum PCBs (928.6 and 491.0 ng/g) wet weight, respectively. Contaminant levels in eggs from St. Clair River AOC were generally higher than those from Algonquin Park, but similar to those from Tiny Marsh. Dioxins appeared highest from the Detroit River. The PCB congener pattern in eggs suggested that turtles from the Detroit River and Wheatley Harbour AOCs were exposed to Aroclor 1260. TEQs of sum PCBs in eggs from all AOCs and p,p'-DDE levels in eggs from the Wheatley Harbour and the Detroit River AOCs exceeded the Canadian Environmental Quality Guidelines. Furthermore, sum PCBs in eggs from Detroit River and Wheatley Harbour exceeded partial restriction guidelines for consumption. Although estimated PCB body burdens in muscle tissue of females were well below consumption guidelines, estimated residues in liver and adipose were above guidelines for most sites.

Evaluation of immune and stress status in harbour porpoises (Phocoena phocoena): can hormones and mRNA expression levels serve as indicators to assess stress?

PubMed Central

2013-01-01

Background The harbour porpoise is exposed to increasing pressure caused by anthropogenic activities in its marine environment. Numerous offshore wind farms are planned or under construction in the North and Baltic Seas, which will increase underwater noise during both construction and operation. A better understanding of how anthropogenic impacts affect the behaviour, health, endocrinology, immunology and physiology of the animals is thus needed. The present study compares levels of stress hormones and mRNA expression of cytokines and acute-phase proteins in blood samples of harbour porpoises exposed to different levels of stress during handling, in rehabilitation or permanent human care. Free-ranging harbour porpoises, incidentally caught in pound nets in Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in Harderwijk, the Netherlands, and individuals permanently kept in human care in the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL-10 and TNFα, acute-phase proteins haptoglobin and C-reactive protein and the heat shock protein HSP70) were measured using real-time PCR. Results Biomarker expression levels varied between free-ranging animals and porpoises in human care. Hormone and cytokine ranges showed correlations to each other and to the health status of investigated harbour porpoises. Hormone concentrations were higher in free-ranging harbour porpoises than in animals in human care. Adrenaline can be used as a parameter for the initial reaction to acute stress situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators for the following minutes of acute stress. There is evidence for different correlations between production of normetanephrine

What do external consultants from private and not-for-profit companies offer healthcare commissioners? A qualitative study of knowledge exchange

PubMed Central

Wye, Lesley; Brangan, Emer; Cameron, Ailsa; Gabbay, John; Klein, Jonathan H; Anthwal, Rachel; Pope, Catherine

2015-01-01

Objectives The use of external consultants from private and not-for-profit providers in the National Health Service (NHS) is intended to improve the quality of commissioning. The aim of this study was to learn about the support offered to healthcare commissioners, how external consultants and their clients work together and the perceived impact on the quality of commissioning. Setting NHS commissioning organisations and private and not-for-profit providers. Design Mixed methods case study of eight cases. Data collection 92 interviews with external consultants (n=36), their clients (n=47) and others (n=9). Observation of 25 training events and meetings. Documentation, for example, meeting minutes and reports. Analysis Constant comparison. Data were coded, summarised and analysed by the research team with a coding framework to facilitate cross-case comparison. Results In the four contracts presented here, external providers offered technical solutions (eg, software tools), outsourcing and expertise including project management, data interpretation and brokering relationships with experts. In assessing perceived impact on quality of commissioning, two contracts had limited value, one had short-term benefits and one provided short and longer term benefits. Contracts with commissioners actively learning, embedding and applying new skills were more valued. Other elements of success were: (1) addressing clearly agreed problems of relevance to managerial and operational staff (2) solutions co-produced at all organisational levels (3) external consultants working directly with clients to interpret data outputs to inform locally contextualised commissioning strategies. Without explicit knowledge exchange strategies, outsourcing commissioning to external providers resulted in the NHS clients becoming dependent. Conclusions NHS commissioning will be disadvantaged if commissioners both fail to learn in the short term from the knowledge of external providers and in the longer

Fatal Disseminated Toxoplasma gondii Infection in a Captive Harbour Porpoise (Phocoena phocoena).

PubMed

Herder, V; van de Velde, N; Højer Kristensen, J; van Elk, C; Peters, M; Kilwinski, J; Schares, G; Siebert, U; Wohlsein, P

2015-11-01

A 7-year-old female harbour porpoise (Phocoena phocoena), born and held in captivity, suffered from reduced consciousness, imprecise and circling swimming movements and long phases of immobility over a period of 3 weeks. The animal died during treatment in a Danish open sea facility. Pathological examination revealed multifocal pyogranulomatous to necrotizing meningoencephalomyelitis, ganglioneuritis, plexus chorioiditis, myocarditis, hepatitis and adrenalitis with few intralesional protozoal tachyzoites and bradyzoites within cysts. Immunohistochemistry was positive for Toxoplasma gondii antigen within the lesions. Using polymerase chain reaction (PCR), the presence of T. gondii-specific genome fragments was confirmed. A multilocus PCR-restriction fragment length polymorphism analysis using nine unlinked marker regions (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) resulted in the identification of T. gondii type II (variant Apico Type I), which is the T. gondii genotype dominating in Germany. This is the first description of disseminated fatal toxoplasmosis in a captive harbour porpoise that lived in an open sea basin. Surface water contaminated with toxoplasma oocysts is regarded as the most likely source of infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of EMIT and RIA high volume test procedures for THC metabolites in urine utilizing GC/MS confirmation.

PubMed

Abercrombie, M L; Jewell, J S

1986-01-01

Results of EMIT, Abuscreen RIA, and GC/MS tests for THC metabolites in a high volume random urinalysis program are compared. Samples were field tested by non-laboratory personnel with an EMIT system using a 100 ng/mL cutoff. Samples were then sent to the Army Forensic Toxicology Drug Testing Laboratory (WRAMC) at Fort Meade, Maryland, where they were tested by RIA (Abuscreen) using a statistical 100 ng/mL cutoff. Confirmations of all RIA positives were accomplished using a GC/MS procedure. EMIT and RIA results agreed for 91% of samples. Data indicated a 4% false positive rate and a 10% false negative rate for EMIT field testing. In a related study, results for samples which tested positive by RIA for THC metabolites using a statistical 100 ng/mL cutoff were compared with results by GC/MS utilizing a 20 ng/mL cutoff for the THCA metabolite. Presence of THCA metabolite was detected in 99.7% of RIA positive samples. No relationship between quantitations determined by the two tests was found.

DDTs and other chlorinated organic pesticides and polychlorinated biphenyls pollution in the surface sediments of Keratsini harbour, Saronikos gulf, Greece.

PubMed

Galanopoulou, Stavroula; Vgenopoulos, Andreas; Conispoliatis, Nikolaos

2005-05-01

Sediment samples were collected from Keratsini harbour, Saronikos gulf, Greece and were analysed for chlorinated organic pesticides (DDTs, HCB, Lindane) and polychlorinated biphenyls (PCBs). High total DDTs values were detected in all the sediments samples ranging from 9.1 to 75.6 mug/g, dry weight. PCBs concentrations range from 47.8 to 351.8 ng/g. The results and especially the high concentrations of DDTs reflect the influence of the industrial and urban wastes in the pollution for the Keratsini harbour environment.