40 CFR 63.8687 - What performance tests, design evaluations, and other procedures must I use?

Code of Federal Regulations, 2013 CFR

2013-07-01

.... THC = Total hydrocarbon concentration at the combustion device outlet, parts per million by volume... auxiliary fuel, you must use Equation 6 of this section as follows: ER29AP03.005 Where: THC DE = THC... the test method specified in Table 3 to this subpart. THC = Total hydrocarbon concentration at the...

40 CFR 63.8687 - What performance tests, design evaluations, and other procedures must I use?

Code of Federal Regulations, 2011 CFR

2011-07-01

.... THC = Total hydrocarbon concentration at the combustion device outlet, parts per million by volume... auxiliary fuel, you must use Equation 6 of this section as follows: ER29AP03.005 Where: THC DE = THC... the test method specified in Table 3 to this subpart. THC = Total hydrocarbon concentration at the...

Evaluation of the BACTEC MGIT 960 SL DST Kit and the GenoType MTBDRsl Test for Detecting Extensively Drug-resistant Tuberculosis Cases

PubMed Central

Tekin, Kemal; Albay, Ali; Simsek, Hulya; Sig, Ali Korhan; Guney, Mustafa

2017-01-01

Objective: The present study aimed to evaluate the performances of the BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl test for detecting second-line antituberculosis drug resistance in Multidrug-resistant TB (MDR-TB) cases. Materials and Methods: Forty-six MDR-TB strains were studied. Second-line antituberculosis drug resistances were detected using the BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl test. The Middlebrook 7H10 agar proportion method was used as the reference test. Results: The sensitivity and specificity values for the BACTEC MGIT 960 SL DST kit were both 100% for amikacin, kanamycin, capreomycin (4 µg/mL), and ofloxacin; 100% and 95.3%, respectively, for capreomycin (10 µg/mL); and 85.7% and 100%, respectively, for moxifloxacin (0.5 µg/mL). The sensitivity and specificity values for the GenoType MTBDRsl test to detect fluoroquinolone and aminoglycoside/cyclic peptide resistance were 88.9% and 100%, respectively, for ofloxacin and 85.7% and 94.9%, respectively, for moxifloxacin (0.5 µg/mL). The accuracy of the GenoType MTBDRsl assay for kanamycin, capreomycin, ofloxacin, and moxifloxacin was lower than that of the BACTEC MGIT 960 SL DST. Conclusion: The BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl were successful in detecting second-line antituberculosis drug resistance. Preliminary results of the GenoType MTBDRsl are very valuable for early treatment decisions, but we still recommend additional BACTEC MGIT 960 SL DST kit usage in the routine evaluation of drug-resistant tuberculosis. PMID:29123441

Evaluation of the BACTEC MGIT 960 SL DST Kit and the GenoType MTBDRsl Test for Detecting Extensively Drug-resistant Tuberculosis Cases.

PubMed

Tekin, Kemal; Albay, Ali; Simsek, Hulya; Sig, Ali Korhan; Guney, Mustafa

2017-10-01

The present study aimed to evaluate the performances of the BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl test for detecting second-line antituberculosis drug resistance in Multidrug-resistant TB (MDR-TB) cases. Forty-six MDR-TB strains were studied. Second-line antituberculosis drug resistances were detected using the BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl test. The Middlebrook 7H10 agar proportion method was used as the reference test. The sensitivity and specificity values for the BACTEC MGIT 960 SL DST kit were both 100% for amikacin, kanamycin, capreomycin (4 µg/mL), and ofloxacin; 100% and 95.3%, respectively, for capreomycin (10 µg/mL); and 85.7% and 100%, respectively, for moxifloxacin (0.5 µg/mL). The sensitivity and specificity values for the GenoType MTBDRsl test to detect fluoroquinolone and aminoglycoside/cyclic peptide resistance were 88.9% and 100%, respectively, for ofloxacin and 85.7% and 94.9%, respectively, for moxifloxacin (0.5 µg/mL). The accuracy of the GenoType MTBDRsl assay for kanamycin, capreomycin, ofloxacin, and moxifloxacin was lower than that of the BACTEC MGIT 960 SL DST. The BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl were successful in detecting second-line antituberculosis drug resistance. Preliminary results of the GenoType MTBDRsl are very valuable for early treatment decisions, but we still recommend additional BACTEC MGIT 960 SL DST kit usage in the routine evaluation of drug-resistant tuberculosis.

Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity

PubMed Central

Britch, Stevie C.; Wiley, Jenny L.; Yu, Zhihao; Clowers, Brian H.; Craft, Rebecca M.

2017-01-01

Background Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ9-tetrahydrocannabinol’s (THC) effects. The current study examined sex differences in CBD-THC interactions on antinociception, locomotion, and THC metabolism. Methods In Experiment 1, CBD (0, 10 or 30 mg/kg) was administered 15 min before THC (0, 1.8, 3.2, 5.6 or10 mg/kg), and rats were tested for antinociception and locomotion 15–360 min post-THC injection. In Experiments 2 and 3, CBD (30 mg/kg) was administered 13 hr or 15 min before THC (1.8 mg/kg); rats were tested for antinociception and locomotion 30–480 min post-THC injection (Experiment 2), or serum samples were taken 30–360 min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3). Results In Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC-induced paw pressure but not tail withdrawal antinociception 4–6 hr post-THC injection. CBD alone increased locomotor activity at 6 hr post-injection, but enhanced THC-induced hypolocomotion 4–6 hr post-THC injection, at lower THC doses. There were no sex differences in CBD-THC interactions. In Experiments 2 and 3, CBD did not significantly enhance THC’s effects when CBD was administered 13 hr or 15 min before THC; however, CBD inhibited THC metabolism, and this effect was greater in females than males. Conclusions These results suggest that CBD may enhance THC’s antinociceptive and hypolocomotive effects, primarily prolonging THC’s duration of action; however, these effects were small and inconsistent across experiments. CBD inhibition of THC metabolism as well other mechanisms likely contribute to CBD-THC interactions on behavior. PMID:28445853

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...

40 CFR 86.159-00 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and... analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All official US06 tests shall be... pumps, the temperature recorder, the vehicle cooling fan, and the heated THC analysis recorder (diesel...

40 CFR 86.159-00 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and... analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All official US06 tests shall be... pumps, the temperature recorder, the vehicle cooling fan, and the heated THC analysis recorder (diesel...

40 CFR 86.159-00 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and... analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All official US06 tests shall be... pumps, the temperature recorder, the vehicle cooling fan, and the heated THC analysis recorder (diesel...

40 CFR 86.159-00 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and... analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All official US06 tests shall be... pumps, the temperature recorder, the vehicle cooling fan, and the heated THC analysis recorder (diesel...

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 roadside drug testing within 2-3h of use. Confirmatory analysis can identify Sativex(®) treatment through use of THC/CBD ratios, however, these ratios would unlikely be sufficient to differentiate non-medicinal cannabis use from Sativex(®) use if both are taken concurrently. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2010 CFR

2010-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2012 CFR

2012-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 63.1512 - Performance test/compliance demonstration requirements and procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... operator must conduct a performance test to measure THC and D/F emissions at the outlet of the control.../decoating kiln. The owner or operator must conduct performance tests to measure emissions of THC, D/F, HCl... operating temperature of each afterburner every 15 minutes during the THC and D/F performance tests; (ii...

40 CFR 63.1512 - Performance test/compliance demonstration requirements and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... operator must conduct a performance test to measure THC and D/F emissions at the outlet of the control.../decoating kiln. The owner or operator must conduct performance tests to measure emissions of THC, D/F, HCl... operating temperature of each afterburner every 15 minutes during the THC and D/F performance tests; (ii...

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.

Simple, direct drug susceptibility testing technique for diagnosis of drug-resistant tuberculosis in resource-poor settings.

PubMed

Kim, C-K; Joo, Y-T; Lee, E P; Park, Y K; Kim, H-J; Kim, S J

2013-09-01

The Korean Institute of Tuberculosis, Seoul, Republic of Korea. To develop a simple, direct drug susceptibility testing (DST) technique using Kudoh-modified Ogawa (KMO) medium. The critical concentrations of isoniazid (INH), rifampicin (RMP), kanamycin (KM) and ofloxacin (OFX) for KMO medium were calibrated by comparing the minimal inhibitory concentrations (MICs) against clinical isolates of Mycobacterium tuberculosis on KMO with those on Löwenstein-Jensen (LJ). The performance of the direct KMO DST technique was evaluated on 186 smear-positive sputum specimens and compared with indirect LJ DST. Agreement of MICs on direct vs. indirect DST was high for INH, RMP and OFX. KM MICs on KMO were ∼10 g/ml higher than those on LJ. The critical concentrations of INH, RMP, OFX and KM for KMO were therefore set at 0.2, 40.0, 2.0, and 40.0 g/ml. The evaluation of direct DST of smear-positive sputum specimens showed 100% agreement with indirect LJ DST for INH and RMP. However, the respective susceptible and resistant predictive values were 98.8% and 100% for OFX, and 100% and 80% for KM. Direct DST using KMO is useful, with clear advantages of a shorter turnaround time, procedural simplicity and low cost compared to indirect DST. It may be most indicated in resource-poor settings for programmatic management of drug-resistant tuberculosis.

40 CFR 63.9800 - How do I conduct performance tests and establish operating limits?

Code of Federal Regulations, 2014 CFR

2014-07-01

... determine compliance with the total hydrocarbon (THC) emission concentration limit listed in Table 1 to this... using Equation 1 of this section: ER16AP03.000 Where: C THC-C = THC concentration, corrected to 18 percent oxygen, parts per million by volume, dry basis (ppmvd) C THC = THC concentration (uncorrected...

Association between posttest dexamethasone and cortisol concentrations in the 1 mg overnight dexamethasone suppression test.

PubMed

Asvold, Bjørn O; Grill, Valdemar; Thorstensen, Ketil; Bjørgaas, Marit R

2012-11-01

It has been suggested that comparison of posttest dexamethasone and cortisol concentrations may improve the evaluation of the dexamethasone suppression test (DST) for Cushing's syndrome. In particular, this would be reasonable if posttest cortisol differs by dexamethasone levels within the range that is usually attained in the DST. Using fractional polynomial regression, we therefore studied the association between posttest 0800 h dexamethasone and cortisol levels in 53 subjects without Cushing's syndrome who were tested with the 1 mg overnight DST. Plasma dexamethasone was associated with plasma cortisol (P<0.001), and the regression line suggested a strong negative association related to dexamethasone levels <5 nmol/l. However, among the 94% of subjects with plasma dexamethasone >5.0 nmol/l, there was no association between dexamethasone and cortisol levels (P=0.55). In conclusion, subjects tested with the 1 mg overnight DST usually attain an 0800 h plasma dexamethasone >5 nmol/l, and plasma cortisol does not differ by plasma dexamethasone in these subjects. This suggests that routine comparison of dexamethasone and cortisol levels may not be a useful approach to improve the performance of the 1 mg DST. However, dexamethasone measurements may identify subjects with inadequately low plasma dexamethasone and may therefore be of value when retesting subjects with possibly false-positive DST results.

Association between posttest dexamethasone and cortisol concentrations in the 1 mg overnight dexamethasone suppression test

PubMed Central

Åsvold, Bjørn O; Grill, Valdemar; Thorstensen, Ketil; Bjørgaas, Marit R

2012-01-01

It has been suggested that comparison of posttest dexamethasone and cortisol concentrations may improve the evaluation of the dexamethasone suppression test (DST) for Cushing's syndrome. In particular, this would be reasonable if posttest cortisol differs by dexamethasone levels within the range that is usually attained in the DST. Using fractional polynomial regression, we therefore studied the association between posttest 0800 h dexamethasone and cortisol levels in 53 subjects without Cushing's syndrome who were tested with the 1 mg overnight DST. Plasma dexamethasone was associated with plasma cortisol (P<0.001), and the regression line suggested a strong negative association related to dexamethasone levels <5 nmol/l. However, among the 94% of subjects with plasma dexamethasone >5.0 nmol/l, there was no association between dexamethasone and cortisol levels (P=0.55). In conclusion, subjects tested with the 1 mg overnight DST usually attain an 0800 h plasma dexamethasone >5 nmol/l, and plasma cortisol does not differ by plasma dexamethasone in these subjects. This suggests that routine comparison of dexamethasone and cortisol levels may not be a useful approach to improve the performance of the 1 mg DST. However, dexamethasone measurements may identify subjects with inadequately low plasma dexamethasone and may therefore be of value when retesting subjects with possibly false-positive DST results. PMID:23781306

Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms.

PubMed

Bruce, Kenneth R; Steiger, Howard; Israël, Mimi; Groleau, Patricia; Ng Ying Kin, N M K; Ouellette, Anne-Sophie; Sycz, Lindsay; Badawi, Ghislaine

2012-08-07

Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations. Copyright © 2012 Elsevier Inc. All rights reserved.

Delayed and Unreported Drug-Susceptibility Testing Results in the US National Tuberculosis Surveillance System, 1993-2014.

PubMed

Jones, Jefferson Michael; Armstrong, Lori R

Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. DST is recommended for all culture-confirmed cases of tuberculosis. We examined trends in delayed and unreported DST results in the Centers for Disease Control and Prevention's National Tuberculosis Surveillance System. We analyzed culture-confirmed tuberculosis cases reported to the National Tuberculosis Surveillance System during 1993-2014 for annual trends in initial DST reporting for first-line antituberculosis drugs and trends in on-time, delayed, and unreported results. We defined on-time reporting as DST results received during the same calendar year in which the patient's case was reported or ≤4 months after the calendar year ended and delayed reporting as DST results received after the calendar year. We compared cases with on-time, delayed, and unreported DST results by patient and tuberculosis program characteristics. The proportion of cases with reported results for all first-line antituberculosis drugs increased during 1993-2011. Reporting of pyrazinamide results was lower than reporting of other drugs. However, during 2000-2012, of 134 787 tuberculosis cases reported to the National Tuberculosis Surveillance System, reporting was on time for 125 855 (93.4%) cases, delayed for 5332 (4.0%) cases, and unreported for 3600 (2.7%) cases. Despite increases in the proportion of cases with on-time DST results, delayed and unreported results persisted. Carefully assessing causes for delayed and unreported DST results should lead to more timely reporting of drug-resistant tuberculosis.

40 CFR 63.9800 - How do I conduct performance tests and establish operating limits?

Code of Federal Regulations, 2012 CFR

2012-07-01

... determine compliance with the total hydrocarbon (THC) emission concentration limit listed in Table 1 to this... using Equation 1 of this section: ER16AP03.000 Where: C THC-C=THC concentration, corrected to 18 percent oxygen, parts per million by volume, dry basis (ppmvd) C THC=THC concentration (uncorrected), ppmvd CO2...

40 CFR 63.9800 - How do I conduct performance tests and establish operating limits?

Code of Federal Regulations, 2013 CFR

2013-07-01

... determine compliance with the total hydrocarbon (THC) emission concentration limit listed in Table 1 to this... using Equation 1 of this section: ER16AP03.000 Where: C THC-C=THC concentration, corrected to 18 percent oxygen, parts per million by volume, dry basis (ppmvd) C THC=THC concentration (uncorrected), ppmvd CO2...

40 CFR 63.9800 - How do I conduct performance tests and establish operating limits?

Code of Federal Regulations, 2011 CFR

2011-07-01

... determine compliance with the total hydrocarbon (THC) emission concentration limit listed in Table 1 to this... using Equation 1 of this section: ER16AP03.000 Where: C THC-C=THC concentration, corrected to 18 percent oxygen, parts per million by volume, dry basis (ppmvd) C THC=THC concentration (uncorrected), ppmvd CO2...

40 CFR 63.9800 - How do I conduct performance tests and establish operating limits?

Code of Federal Regulations, 2010 CFR

2010-07-01

... determine compliance with the total hydrocarbon (THC) emission concentration limit listed in Table 1 to this... using Equation 1 of this section: ER16AP03.000 Where: C THC-C=THC concentration, corrected to 18 percent oxygen, parts per million by volume, dry basis (ppmvd) C THC=THC concentration (uncorrected), ppmvd CO2...

Development of a Low Strain-Rate Gun Propellant Bed Compression Test and its Use in Evaluating Mechanical Response

DTIC Science & Technology

2016-09-01

heuristics, die and propellant geometries from similar facilities reported in the literature [2,3] and the DST Group design .  bed* (mm) φbed...compliance curves from the experimental data. In UNCLASSIFIED DST- Group -TR-3291 UNCLASSIFIED 18 Figure 13, the red axial compliance traces were...UNCLASSIFIED DST- Group -TR-3291 UNCLASSIFIED 46 At a test temperature of -60˚C, the equivalent strain rates are within the 10 to 500 s-1 given in

Gonadal hormone modulation of Δ9-tetrahydrocannabinol-induced antinociception and metabolism in female versus male rats

PubMed Central

Craft, R.M.; Haas, A.E.; Wiley, J.L.; Yu, Z.; Clowers, B.H.

2016-01-01

The gonadal hormones testosterone (T) in adult males and estradiol (E2) in adult females have been reported to modulate behavioral effects of Δ9-tetrahydrocannabinol (THC). This study determined whether activational effects of T and E2 are sex-specific, and whether hormones modulate production of the active metabolite 11-hydroxy-THC (11-OH-THC) and the inactive metabolite 11-nor-9-carboxy-THC (THC-COOH). Adult male and female rats were gonadectomized (GDX) and treated with nothing (0), T (10-mm Silastic capsule/100 g body weight), or E2 (1-mm Silastic capsule/rat). Three weeks later, saline or the cytochrome P450 inhibitor proadifen (25 mg/kg; to block THC metabolism and boost THC's effects) was injected i.p.; one h later, vehicle or THC (3 mg/kg females, 5 mg/kg males) was injected i.p., and rats were tested for antinociceptive and motoric effects 15-240 min post-injection. T did not consistently alter THC-induced antinociception in males, but decreased it in females (tail withdrawal test). Conversely, T decreased THC-induced catalepsy in males, but had no effect in females. E2 did not alter THC-induced antinociception in females, but enhanced it in males. The discrepant effects of T and E2 on males’ and females’ behavioral responses to THC suggests that sexual differentiation of THC sensitivity is not simply due to activational effects of hormones, but also occurs via organizational hormone or sex chromosome effects. Analysis of serum showed that proadifen increased THC levels, E2 increased 11-OH-THC in GDX males, and T decreased 11-OH-THC (and to a lesser extent, THC) in GDX females. Thus, hormone modulation of THC's behavioral effects is caused in part by hormone modulation of THC oxidation to its active metabolite. However, the fact that hormone modulation of metabolism did not alter THC sensitivity similarly on all behavioral measures within each sex suggests that other mechanisms also play a role in gonadal hormone modulation of THC sensitivity in adult rats. PMID:27670094

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

PubMed

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

2008-06-01

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

Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test.

PubMed

Ueland, Grethe Å; Methlie, Paal; Kellmann, Ralf; Bjørgaas, Marit; Åsvold, Bjørn O; Thorstensen, Ketil; Kelp, Oskar; Thordarson, Hrafnkell B; Mellgren, Gunnar; Løvås, Kristian; Husebye, Eystein S

2017-06-01

The overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum. Prospective study of DST was carried out in patients with suspected Cushing's syndrome (CS) ( n  = 49), incidentaloma ( n  = 152) and healthy controls ( n  = 101). Cortisol, cortisone and DXM were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST ( n  = 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort ( n  = 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol. Simultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS. © 2017 European Society of Endocrinology.

40 CFR 1066.15 - Overview of test procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ways: (i) Total hydrocarbons, THC. (ii) Nonmethane hydrocarbons, NMHC, which results from subtracting methane (CH4) from THC. (iii) Total hydrocarbon-equivalent, THCE, which results from adjusting THC...

40 CFR 1066.15 - Overview of test procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ways: (i) Total hydrocarbons, THC. (ii) Nonmethane hydrocarbons, NMHC, which results from subtracting methane (CH4) from THC. (iii) Total hydrocarbon-equivalent, THCE, which results from adjusting THC...

Use of an automated decision support tool optimizes clinicians' ability to interpret and appropriately respond to structured self-monitoring of blood glucose data.

PubMed

Rodbard, Helena W; Schnell, Oliver; Unger, Jeffrey; Rees, Christen; Amstutz, Linda; Parkin, Christopher G; Jelsovsky, Zhihong; Wegmann, Nathan; Axel-Schweitzer, Matthias; Wagner, Robin S

2012-04-01

We evaluated the impact of an automated decision support tool (DST) on clinicians' ability to identify glycemic abnormalities in structured self-monitoring of blood glucose (SMBG) data and then make appropriate therapeutic changes based on the glycemic patterns observed. In this prospective, randomized, controlled, multicenter study, 288 clinicians (39.6% family practice physicians, 37.9% general internal medicine physicians, and 22.6% nurse practitioners) were randomized to structured SMBG alone (STG; n = 72); structured SMBG with DST (DST; n = 72); structured SMBG with an educational DVD (DVD; n = 72); and structured SMBG with DST and the educational DVD (DST+DVD; n = 72). Clinicians analyzed 30 patient cases (type 2 diabetes), identified the primary abnormality, and selected the most appropriate therapy. A total of 222 clinicians completed all 30 patient cases with no major protocol deviations. Significantly more DST, DVD, and DST+DVD clinicians correctly identified the glycemic abnormality and selected the most appropriate therapeutic option compared with STG clinicians: 49, 51, and 55%, respectively, vs. 33% (all P < 0.0001) with no significant differences among DST, DVD, and DST+DVD clinicians. Use of structured SMBG, combined with the DST, the educational DVD, or both, enhances clinicians' ability to correctly identify significant glycemic patterns and make appropriate therapeutic decisions to address those patterns. Structured testing interventions using either the educational DVD or the DST are equally effective in improving data interpretation and utilization. The DST provides a viable alternative when comprehensive education is not feasible, and it may be integrated into medical practices with minimal training.

40 CFR 63.865 - Performance test requirements and test methods.

Code of Federal Regulations, 2013 CFR

2013-07-01

... follows: ER18FE03.012 Where: ERSCCU = THC emission rate reported as carbon from each semichemical combustion unit, kg/Mg (lb/ton) of black liquor solids fired; THCmeas = Measured THC mass emission rate... semichemical combustion unit has selected the percentage reduction standards for THC, under § 63.862(c)(2)(ii...

40 CFR 63.865 - Performance test requirements and test methods.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Where: ERSCCU = THC emission rate reported as carbon from each semichemical combustion unit, kg/Mg (lb/ton) of black liquor solids fired; THCmeas = Measured THC mass emission rate reported as carbon, kg/hr... unit has selected the percentage reduction standards for THC, under § 63.862(c)(2)(ii), the percentage...

40 CFR 86.127-00 - Test procedures; overview.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and gaseous- fueled... vehicles). (b) The FTP Otto-cycle exhaust emission test is designed to determine gaseous THC, CO, CO2, CH4... determine gaseous THC, NMHC, CO, CO2, CH4, and NOX emissions from gasoline-fueled or diesel-fueled vehicles...

40 CFR 86.127-96 - Test procedures; overview.

Code of Federal Regulations, 2012 CFR

2012-07-01

... or all of the following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and... gaseous-fueled vehicles). (b) The Otto-cycle exhaust emission test is designed to determine gaseous THC... analyzed for THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, and...

40 CFR 86.127-96 - Test procedures; overview.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or all of the following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and... gaseous-fueled vehicles). (b) The Otto-cycle exhaust emission test is designed to determine gaseous THC... analyzed for THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, and...

40 CFR 63.1349 - Performance testing requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... in accordance with § 63.1346(c)(1). (4) THC emissions test. (i) If you are subject to limitations on THC emissions, you must operate a CEMS in accordance with the requirements in § 63.1350(i). For the purposes of conducting the accuracy and quality assurance evaluations for CEMS, the THC span value (as...

40 CFR 86.127-96 - Test procedures; overview.

Code of Federal Regulations, 2013 CFR

2013-07-01

... or all of the following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and... gaseous-fueled vehicles). (b) The Otto-cycle exhaust emission test is designed to determine gaseous THC... analyzed for THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, and...

40 CFR 86.127-00 - Test procedures; overview.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and gaseous- fueled... vehicles). (b) The FTP Otto-cycle exhaust emission test is designed to determine gaseous THC, CO, CO2, CH4... determine gaseous THC, NMHC, CO, CO2, CH4, and NOX emissions from gasoline-fueled or diesel-fueled vehicles...

40 CFR 86.127-96 - Test procedures; overview.

Code of Federal Regulations, 2011 CFR

2011-07-01

... or all of the following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and... gaseous-fueled vehicles). (b) The Otto-cycle exhaust emission test is designed to determine gaseous THC... analyzed for THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, and...

40 CFR 86.127-00 - Test procedures; overview.

Code of Federal Regulations, 2012 CFR

2012-07-01

... following emissions: (1) Gaseous exhaust THC, CO, NOX. CO2 (for petroleum-fueled and gaseous- fueled... vehicles). (b) The FTP Otto-cycle exhaust emission test is designed to determine gaseous THC, CO, CO2, CH4... determine gaseous THC, NMHC, CO, CO2, CH4, and NOX emissions from gasoline-fueled or diesel-fueled vehicles...

40 CFR 63.865 - Performance test requirements and test methods.

Code of Federal Regulations, 2012 CFR

2012-07-01

... follows: ER18FE03.012 Where: ERSCCU = THC emission rate reported as carbon from each semichemical combustion unit, kg/Mg (lb/ton) of black liquor solids fired; THCmeas = Measured THC mass emission rate... semichemical combustion unit has selected the percentage reduction standards for THC, under § 63.862(c)(2)(ii...

In Vitro Stability of Free and Glucuronidated Cannabinoids in Blood and Plasma Following Controlled Smoked Cannabis

PubMed Central

Karschner, Erin L.; Desrosiers, Nathalie A.; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

BACKGROUND Blood and plasma cannabinoid stability is important for test interpretation and is best studied in authentic rather than fortified samples. METHODS Low and high blood and plasma pools were created for each of 10 participants after they smoked a cannabis cigarette. The stabilities of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide, and THCCOOH-glucuronide were determined after 1 week at room temperature; 1, 2, 4, 12, and 26 (±2) weeks at 4 °C; and 1, 2, 4, 12, 26 (±2), and 52 (±4) weeks at −20 °C. Stability was assessed by Friedman test. RESULTS Numbers of THC-glucuronide and CBD-positive blood samples were insufficient to assess stability. In blood, 11-OH-THC and CBN were stable for 1 week at room temperature, whereas THC and THCCOOH-glucuronide decreased and THCCOOH increased. In blood, THC, THCCOOH-glucuronide, THCCOOH, 11-OH-THC, and CBN were stable for 12, 4, 4, 12, and 26 weeks, respectively, at 4 °C and 12, 12, 26, 26, and 52 weeks at −20 °C. In plasma, THC-glucuronide, THC, CBN, and CBD were stable for 1 week at room temperature, whereas THCCOOH-glucuronide and 11-OH-THC decreased and THCCOOH increased. In plasma, THC-glucuronide, THC, THCCOOH-glucuronide, THCCOOH, 11-OH-THC, CBN, and CBD were stable for 26, 26, 2, 2, 26, 12, and 26 weeks, respectively, at 4 °C and 52, 52, 26, 26, 52, 52, and 52 weeks, respectively, at −20 °C. CONCLUSIONS Blood and plasma samples should be stored at −20 °C for no more than 3 and 6 months, respectively, to assure accurate cannabinoid quantitative results. PMID:23519966

40 CFR 63.6620 - What performance tests and other procedures must I use?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Where: Ci = concentration of carbon monoxide (CO), total hydrocarbons (THC), or formaldehyde at the control device inlet, Co = concentration of CO, THC, or formaldehyde at the control device outlet, and R = percent reduction of CO, THC, or formaldehyde emissions. (2) You must normalize the CO, THC, or...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

..., THC destruction efficiency, THC outlet concentration, or combustion efficiency standards, the sampling... combustion efficiency or THC standards a. Measure the concentration of carbon dioxideb. Measure the... method 25A in appendix A to part 60 of this chapter 10. Each control device used to comply with the THC...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

..., THC destruction efficiency, THC outlet concentration, or combustion efficiency standards, the sampling... combustion efficiency or THC standards a. Measure the concentration of carbon dioxideb. Measure the... method 25A in appendix A to part 60 of this chapter 10. Each control device used to comply with the THC...

40 CFR 63.6620 - What performance tests and other procedures must I use?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Where: Ci = concentration of carbon monoxide (CO), total hydrocarbons (THC), or formaldehyde at the control device inlet, Co = concentration of CO, THC, or formaldehyde at the control device outlet, and R = percent reduction of CO, THC, or formaldehyde emissions. (2) You must normalize the CO, THC, or...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

..., THC destruction efficiency, THC outlet concentration, or combustion efficiency standards, the sampling... combustion efficiency or THC standards a. Measure the concentration of carbon dioxideb. Measure the... method 25A in appendix A to part 60 of this chapter 10. Each control device used to comply with the THC...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

..., THC destruction efficiency, THC outlet concentration, or combustion efficiency standards, the sampling... combustion efficiency or THC standards a. Measure the concentration of carbon dioxideb. Measure the... method 25A in appendix A to part 60 of this chapter 10. Each control device used to comply with the THC...

40 CFR Table 4 to Subpart Lllll of... - Initial Compliance With Emission Limitations

Code of Federal Regulations, 2011 CFR

2011-07-01

... auxiliary fuel achieving a THC destruction efficiency of 95.8 percent i. The THC destruction efficiency of..., and total hydrocarbon outlet concentrations over the performance test during which the THC destruction... table. c. Route the emissions to a combustion device that does not use auxiliary fuel achieving a THC...

40 CFR 86.137-94 - Dynamometer test run, gaseous and particulate emissions.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., if applicable), the temperature recorder, the vehicle cooling fan, and the heated THC analysis... diesel-cycle THC analyzer continuous sample line and filter, methanol-fueled vehicle THC, methanol and... measuring devices to zero. (i) For gaseous bag samples (except THC samples), the minimum flow rate is 0.17...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

..., THC destruction efficiency, THC outlet concentration, or combustion efficiency standards, the sampling... combustion efficiency or THC standards a. Measure the concentration of carbon dioxideb. Measure the... method 25A in appendix A to part 60 of this chapter 10. Each control device used to comply with the THC...

40 CFR Table 4 to Subpart Lllll of... - Initial Compliance With Emission Limitations

Code of Federal Regulations, 2013 CFR

2013-07-01

... auxiliary fuel achieving a THC destruction efficiency of 95.8 percent i. The THC destruction efficiency of..., and total hydrocarbon outlet concentrations over the performance test during which the THC destruction... table. c. Route the emissions to a combustion device that does not use auxiliary fuel achieving a THC...

40 CFR Table 4 to Subpart Lllll of... - Initial Compliance With Emission Limitations

Code of Federal Regulations, 2010 CFR

2010-07-01

... auxiliary fuel achieving a THC destruction efficiency of 95.8 percent i. The THC destruction efficiency of..., and total hydrocarbon outlet concentrations over the performance test during which the THC destruction... table. c. Route the emissions to a combustion device that does not use auxiliary fuel achieving a THC...

40 CFR Table 4 to Subpart Lllll of... - Initial Compliance With Emission Limitations

Code of Federal Regulations, 2012 CFR

2012-07-01

... auxiliary fuel achieving a THC destruction efficiency of 95.8 percent i. The THC destruction efficiency of..., and total hydrocarbon outlet concentrations over the performance test during which the THC destruction... table. c. Route the emissions to a combustion device that does not use auxiliary fuel achieving a THC...

40 CFR 86.137-94 - Dynamometer test run, gaseous and particulate emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., if applicable), the temperature recorder, the vehicle cooling fan, and the heated THC analysis... diesel-cycle THC analyzer continuous sample line and filter, methanol-fueled vehicle THC, methanol and... measuring devices to zero. (i) For gaseous bag samples (except THC samples), the minimum flow rate is 0.17...

40 CFR Table 4 to Subpart Lllll of... - Initial Compliance With Emission Limitations

Code of Federal Regulations, 2014 CFR

2014-07-01

... auxiliary fuel achieving a THC destruction efficiency of 95.8 percent i. The THC destruction efficiency of..., and total hydrocarbon outlet concentrations over the performance test during which the THC destruction... table. c. Route the emissions to a combustion device that does not use auxiliary fuel achieving a THC...

Overexpression of a Chimeric Gene, OsDST-SRDX, Improved Salt Tolerance of Perennial Ryegrass

PubMed Central

Cen, Huifang; Ye, Wenxing; Liu, Yanrong; Li, Dayong; Wang, Kexin; Zhang, Wanjun

2016-01-01

The Drought and Salt Tolerance gene (DST) encodes a C2H2 zinc finger transcription factor, which negatively regulates salt tolerance in rice (Oryza sativa). Phylogenetic analysis of six homologues of DST genes in different plant species revealed that DST genes were conserved evolutionarily. Here, the rice DST gene was linked to an SRDX domain for gene expression repression based on the Chimeric REpressor gene-Silencing Technology (CRES-T) to make a chimeric gene (OsDST-SRDX) construct and introduced into perennial ryegrass by Agrobacterium-mediated transformation. Integration and expression of the OsDST-SRDX in transgenic plants were tested by PCR and RT-PCR, respectively. Transgenic lines overexpressing the OsDST-SRDX fusion gene showed obvious phenotypic differences and clear resistance to salt-shock and to continuous salt stresses compared to non-transgenic plants. Physiological analyses including relative leaf water content, electrolyte leakage, proline content, malondialdehyde (MDA) content, H2O2 content and sodium and potassium accumulation indicated that the OsDST-SRDX fusion gene enhanced salt tolerance in transgenic perennial ryegrass by altering a wide range of physiological responses. To our best knowledge this study is the first report of utilizing Chimeric Repressor gene-Silencing Technology (CRES-T) in turfgrass and forage species for salt-tolerance improvement. PMID:27251327

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.

Sex-dimorphic psychomotor activation after perinatal exposure to (-)-delta 9-tetrahydrocannabinol. An ontogenic study in Wistar rats.

PubMed

Navarro, M; Rubio, P; Rodríguez de Fonseca, F

1994-12-01

The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

40 CFR 60.5413 - What are the performance testing procedures for control devices used to demonstrate compliance at...

Code of Federal Regulations, 2013 CFR

2013-07-01

... to or less than 10.0 parts per million by volume-wet THC as propane corrected to 3.0 percent carbon... 2A at 40 CFR part 60, appendix A-1. Record the start and stop reading for each 60-minute THC test. Record the gas pressure and temperature at 5-minute intervals throughout each 60-minute THC test. (iii...

[Testing the pharmacological activity of some synthetic cannabinoids in mice (author's transl)].

PubMed

Ganz, A J; Waser, P G

1980-01-01

A series of synthetic cannabinoids were tested in mice for analgesic, anticonvulsant, sedative and reserpine antagonistic properties as well as for influence on body temperature and on motor coordination and compared with the natural delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol (delta 8-THC) and cannabidiol (CBD). All cannabinoids were injected s.c. or i.p. in mice as solutions in olive oil. The synthetic cannabinoids, with the exception of the lipophilic ones, were less active than the natural delta 9-THC. 1',1'-dimethyl-delta 8-tetrahydrocannabinol (DM-delta 8-THC) has an analgesic ED 50 of 16 mg/kg s.c. (writhing test) and is three times more active than delta 9-THC, but also eight times less active than morphine. The lipophilic derivatives of delta 8-THC prolonged pentobarbitone narcosis and diminished locomotor activity in mice. Anticonvulsant activities could never be detected; all cannabinoids slightly diminished body temperature and antagonized weakly the hypothermia induced by reserpine. The trained capacity of remaining on the rotating rod was severely shortened for a long time after application of all cannabinoids but mainly by the lipophilic ones. The influence of derivation on the activity of delta 9-THC is discussed.

BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis exposure and host susceptibility interaction.

PubMed

Segal-Gavish, Hadar; Gazit, Neta; Barhum, Yael; Ben-Zur, Tali; Taler, Michal; Hornfeld, Shay Henry; Gil-Ad, Irit; Weizman, Abraham; Slutsky, Inna; Niwa, Minae; Kamiya, Atsushi; Sawa, Akira; Offen, Daniel; Barzilay, Ran

2017-07-01

Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations. Wild-Type and dominant-negative-DISC1 (DN-DISC1) mice were injected with THC (10 mg/kg) or vehicle for 10 days during mid-adolescence-equivalent period. Behavioral tests were conducted to assess exploratory activity (open field test, light-dark box test) and cognitive function (novel object recognition test). Electrophysiological effect of THC was evaluated using acute hippocampal slices, and hippocampal cannabinoid receptor type 1 and brain-derived neurotrophic factor (BDNF) protein levels were measured. Our results indicate that THC exposure elicits deficits in exploratory activity and recognition memory, together with reduced short-term synaptic facilitation and loss of BDNF surge in the hippocampus of DN-DISC mice, but not in wild-type mice. Over-expression of BDNF in the hippocampus of THC-treated DN-DISC1 mice prevented the impairment in recognition memory. The results of this study imply that induction of BDNF following adolescence THC exposure may serve as a homeostatic response geared to maintain proper cognitive function against exogenous insult. The BDNF surge in response to THC is perturbed in the presence of mutant DISC1, suggesting DISC1 may be a useful probe to identify biological cascades involved in the neurochemical, electrophysiological, and behavioral effects of cannabis related psychiatric manifestations. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

40 CFR 86.158-08 - Supplemental Federal Test Procedures; overview.

Code of Federal Regulations, 2012 CFR

2012-07-01

... THC, CO, NOX, CH4, and CO2. For diesel-cycle vehicles, THC is sampled and analyzed continuously... for which THC is sampled and analyzed continuously according to the provisions of § 86.110, the analytical system shall be configured to calculate THC for the US06 City phase and the US06 Highway phase as...

40 CFR Table 4 to Subpart Dddd of... - Requirements for Performance Tests

Code of Federal Regulations, 2010 CFR

2010-07-01

... THC compliance option measure emissions of total HAP as THC Method 25A in appendix A to 40 CFR part 60... the methane emissions from the emissions of total HAP as THC. (6) each process unit subject to a... § 63.2240(c) establish the site-specific operating requirements (including the parameter limits or THC...

40 CFR 86.158-08 - Supplemental Federal Test Procedures; overview.

Code of Federal Regulations, 2014 CFR

2014-07-01

... THC, CO, NOX, CH4, and CO2. For diesel-cycle vehicles, THC is sampled and analyzed continuously... for which THC is sampled and analyzed continuously according to the provisions of § 86.110, the analytical system shall be configured to calculate THC for the US06 City phase and the US06 Highway phase as...

40 CFR 86.158-08 - Supplemental Federal Test Procedures; overview.

Code of Federal Regulations, 2013 CFR

2013-07-01

... THC, CO, NOX, CH4, and CO2. For diesel-cycle vehicles, THC is sampled and analyzed continuously... for which THC is sampled and analyzed continuously according to the provisions of § 86.110, the analytical system shall be configured to calculate THC for the US06 City phase and the US06 Highway phase as...

40 CFR Table 4 to Subpart Dddd of... - Requirements for Performance Tests

Code of Federal Regulations, 2011 CFR

2011-07-01

... THC compliance option measure emissions of total HAP as THC Method 25A in appendix A to 40 CFR part 60... the methane emissions from the emissions of total HAP as THC. (6) each process unit subject to a... § 63.2240(c) establish the site-specific operating requirements (including the parameter limits or THC...

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.

Cognitive function and mood in MDMA/THC users, THC users and non-drug using controls.

PubMed

Lamers, C T J; Bechara, A; Rizzo, M; Ramaekers, J G

2006-03-01

Repeated ecstasy (MDMA) use is reported to impair cognition and cause increased feelings of depression and anxiety. Yet, many relevant studies have failed to control for use of drugs other than MDMA, especially marijuana (THC). To address these confounding effects we compared behavioural performance of 11 MDMA/THC users, 15 THC users and 15 non-drug users matched for age and intellect. We tested the hypothesis that reported feelings of depression and anxiety and cognitive impairment (memory, executive function and decision making) are more severe in MDMA/THC users than in THC users. MDMA/THC users reported more intense feelings of depression and anxiety than THC users and non-drug users. Memory function was impaired in both groups of drug users. MDMA/THC users showed slower psychomotor speed and less mental flexibility than non-drug users. THC users exhibited less mental flexibility and performed worse on the decision making task compared to non-drug users but these functions were similar to those in MDMA/THC users. It was concluded that MDMA use is associated with increased feelings of depression and anxiety compared to THC users and non-drug users. THC users were impaired in some cognitive abilities to the same degree as MDMA/THC users, suggesting that some cognitive impairment attributed to MDMA is more likely due to concurrent THC use.

40 CFR 63.6630 - How do I demonstrate initial compliance with the emission limitations, operating limitations, and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... formaldehyde emission limit by testing for THC instead of formaldehyde. The testing must be conducted according to the requirements in Table 4 of this subpart. The average reduction of emissions of THC determined... subpart, or using appendix A to this subpart. (4) If you are demonstrating compliance with the THC percent...

40 CFR 63.6630 - How do I demonstrate initial compliance with the emission limitations, operating limitations, and...

Code of Federal Regulations, 2014 CFR

2014-07-01

... formaldehyde emission limit by testing for THC instead of formaldehyde. The testing must be conducted according to the requirements in Table 4 of this subpart. The average reduction of emissions of THC determined... subpart, or using appendix A to this subpart. (4) If you are demonstrating compliance with the THC percent...

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-acid. The time and temperature for these effects were similar to those used by most laboratories to collect and test specimens. In several cases, the loss of THC-acid was > 94%.

Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer.

PubMed

Inoue, Masayoshi; Maeda, Hajime; Takeuchi, Yukiyasu; Fukuhara, Kenjiro; Shintani, Yasushi; Funakoshi, Yasunobu; Funaki, Soichiro; Nojiri, Takashi; Kusu, Takashi; Kusumoto, Hidenori; Kimura, Toru; Okumura, Meinoshin

2018-04-01

We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.

The Yucca Mountain Project drift scale test

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

Finley, R.E.; Blair, S.C.; Boyle, W.J.

The Yucca Mountain Project is currently evaluating the coupled thermal-mechanical-hydrological-chemical (TMHC) response of the potential repository host rock through an in situ thermal testing program. A drift scale test (DST) was constructed during 1997 and heaters were turned on in December 1997. The DST includes nine canister-sized containers with thirty operating heaters each located within the heated drift (HD) and fifty wing heaters located in boreholes in both ribs with a total power output of nominally 210kW. A total of 147 boreholes (combined length of 3.3 km) houses most of the over 3700 TMHC sensors connected with 201 km ofmore » cabling to a central data acquisition system. The DST is located in the Exploratory Studies Facility in a 5-m diameter drift approximately 50 m in length. Heating will last up to four years and cooling will last another four years. The rock mass surrounding the DST will experience a harsh thermal environment with rock surface temperatures expected to reach a maximum of about 200 C. This paper describes the process of designing the DST. The first 38 m of the 50-m long Heated Drift (HD) is dedicated to collection of data that will lead to a better understanding of the complex coupled TMHC processes in the host rock of the proposed repository. The final 12 m is dedicated to evaluating the interactions between the heated rock mass and cast-in-place (CIP) concrete ground support systems at elevated temperatures. In addition to a description of the DST design, data from site characterization, and a general description of the analyses and analysis approach used to design the test and make pretest predictions are presented. Test-scoping and pretest numerical predictions of one way thermal-hydrologic, thermal-mechanical, and thermal-chemical behaviors have been completed (TRW, 1997a). These analyses suggest that a dry-out zone will be created around the DST and a 10,000 m{sup 3} volume of rock will experience temperatures above 100 C. The HD will experience large stress increases, particularly in the crown of the drift. Thermoelastic displacements of up to about 16 mm are predicted for some thermomechanical gages. Additional analyses using more complex models will be performed during the conduct of the DST and the results compared with measured data.« less

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.

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

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.

40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

Code of Federal Regulations, 2013 CFR

2013-07-01

... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the stack...

40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

Code of Federal Regulations, 2010 CFR

2010-07-01

... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the stack...

40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

Code of Federal Regulations, 2011 CFR

2011-07-01

... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the stack...

40 CFR Table 4 to Subpart Dddd of... - Requirements for Performance Tests

Code of Federal Regulations, 2014 CFR

2014-07-01

... HAP as THC compliance option measure emissions of total HAP as THC Method 25A in appendix A to 40 CFR... subtract the methane emissions from the emissions of total HAP as THC. (6) each process unit subject to a... § 63.2240(c) establish the site-specific operating requirements (including the parameter limits or THC...

40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

Code of Federal Regulations, 2012 CFR

2012-07-01

... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the stack...

40 CFR Table 4 to Subpart Dddd of... - Requirements for Performance Tests

Code of Federal Regulations, 2012 CFR

2012-07-01

... HAP as THC compliance option measure emissions of total HAP as THC Method 25A in appendix A to 40 CFR... subtract the methane emissions from the emissions of total HAP as THC. (6) each process unit subject to a... § 63.2240(c) establish the site-specific operating requirements (including the parameter limits or THC...

40 CFR Table 4 to Subpart Dddd of... - Requirements for Performance Tests

Code of Federal Regulations, 2013 CFR

2013-07-01

... HAP as THC compliance option measure emissions of total HAP as THC Method 25A in appendix A to 40 CFR... subtract the methane emissions from the emissions of total HAP as THC. (6) each process unit subject to a... § 63.2240(c) establish the site-specific operating requirements (including the parameter limits or THC...

40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

Code of Federal Regulations, 2014 CFR

2014-07-01

... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the stack...

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.

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

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.

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:21763331

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 Elsevier Ltd.

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.

A Two-Year Study of Δ 9 Tetrahydrocannabinol Concentrations in Drivers; Part 2: Physiological Signs on Drug Recognition Expert (DRE) and non-DRE Examinations,.

PubMed

Declues, Kari; Perez, Shelli; Figueroa, Ariana

2018-03-01

Whole blood samples were examined for ∆ 9 -Tetrahydrocannabinol (THC) over 2 years in drivers suspected of driving under the influence. Part one of the study examined the link between [THC] and performance on field sobriety tests. This portion examined objective signs, eye examinations and physiological indicators; and their relationship to the presence of THC. Several objective signs were excellent indicators of the presence of THC: red eyes (94%), droopy eyelids (85.6%), affected speech (87.6%), tongue coating (96.2%), and odor of marijuana (82.4%). About 63.6% of THC positive subjects had dialted pupils (room light). THC positive subjects had either rebound dilation or hippus in 88.8% of cases. Pulse and blood pressure (BP) were evaluated to determine any correlation with [THC]. An increased pulse rate correlated well to the presence of THC (88.5%), but not [THC]. BP did not correlate to [THC] and was also a poor indicator of THC in the blood (50% high). © 2017 American Academy of Forensic Sciences.

40 CFR 60.5413 - What are the performance testing procedures for control devices used to demonstrate compliance at...

Code of Federal Regulations, 2014 CFR

2014-07-01

... reading for each 60-minute THC test. Record the gas pressure and temperature at 5-minute intervals... paragraph (d)(8) of this section. (iv) THC must be determined as specified in paragraph (d)(9) of this...) Conduct THC sampling using Method 25A, 40 CFR part 60, appendix A-7, except that the option for locating...

The effect of cannabis on regular cannabis consumers' ability to ride a bicycle.

PubMed

Hartung, Benno; Schwender, Holger; Roth, Eckhard H; Hellen, Florence; Mindiashvili, Nona; Rickert, Annette; Ritz-Timme, Stefanie; Grieser, Almut; Monticelli, Fabio; Daldrup, Thomas

2016-05-01

To assess the effects of cannabis on the ability required to ride a bicycle, repetitive practical cycling tests and medical examinations were carried out before and after inhalative consumption of cannabis. A maximum of three joints with body weight-adapted THC content (300 μg THC per kg body weight) could be consumed by each test subject. Fourteen regular cannabis-consuming test subjects were studied (12 males, 2 females). In summary, only a few driving faults were observed even under the influence of very high THC concentrations. A defined THC concentration that leads to an inability to ride a bicycle cannot be presented. The test subjects showed only slight distinctive features that can be documented using a medical test routinely run for persons under suspicion of driving under the influence of alcohol or drugs.

Cannabis constituents modulate δ9-tetrahydrocannabinol-induced hyperphagia in rats.

PubMed

Farrimond, Jonathan A; Hill, Andrew J; Whalley, Benjamin J; Williams, Claire M

2010-05-01

The hyperphagic effect of Delta9-tetrahydrocannabinol (Delta9THC) in humans and rodents is well known. However, no studies have investigated the importance of Delta9THC composition and any influence other non-Delta9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified Delta9THC, synthetic Delta9THC (dronabinol), and Delta9THC botanical drug substance (Delta9THC-BDS), a Delta9THC-rich standardized extract comparable in composition to recreationally used cannabis. Adult male rats were orally dosed with purified Delta9THC, synthetic Delta9THC, or Delta9THC-BDS, matched for Delta9THC content (0.34-2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following Delta9THC administration. Data were then analyzed in terms of hourly intake and meal patterns. All three Delta9THC substances tested induced significant hyperphagic effects at doses >or=0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified Delta9THC and Delta9THC-BDS. All Delta9THC compounds displayed classical Delta9THC effects on feeding, significantly increasing shortterm intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified Delta9THC and Delta9THC-BDS are due to non-Delta9THC cannabinoids present in Delta9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate Delta9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.

qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients.

PubMed

Araujo, Sergio; Goulart, Luiz Ricardo; Truman, Richard W; Goulart, Isabela Maria B; Vissa, Varalakshmi; Li, Wei; Matsuoka, Masanori; Suffys, Philip; Fontes, Amanda B; Rosa, Patricia S; Scollard, David M; Williams, Diana L

2017-06-01

Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite's stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing. Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy.

A low-Δ9 tetrahydrocannabinol cannabis extract induces hyperphagia in rats.

PubMed

Farrimond, Jonathan A; Whalley, Benjamin J; Williams, Claire M

2010-12-01

Appetite stimulation via partial agonism of cannabinoid type 1 receptors by Δtetrahydrocannabinol (ΔTHC) is well documented and can be modulated by non-ΔTHC phytocannabinoids. ΔTHC concentrations sufficient to elicit hyperphagia induce changes to both appetitive (reduced latency to feed) and consummatory (increased meal one size and duration) behaviours. Here, we show that a cannabis extract containing too little ΔTHC to stimulate appetite can induce hyperphagia solely by increasing appetitive behaviours. Twelve, male Lister hooded rats were presatiated before treatment with a low-ΔTHC cannabis extract (0.5, 1.0, 2.0 and 4.0 mg/kg). Hourly intake and meal pattern data were recorded and analyzed using one-way analyses of variance followed by Bonferroni post-hoc tests. The cannabis extract significantly increased food intake during the first hour of testing (at 4.0 mg/kg) and significantly reduced the latency to feed versus vehicle treatments (at doses ≥1.0 mg/kg). Meal size and duration were unaffected. These results show only the increase in appetitive behaviours, which could be attributed to non-ΔTHC phytocannabinoids in the extract rather than ΔTHC. Although further study is required to determine the constituents responsible for these effects, these results support the presence of non-ΔTHC cannabis constituent(s) that exert a stimulatory effect on appetite and likely lack the detrimental psychoactive effects of ΔTHC.

Oral fluid cannabinoid concentrations following controlled smoked cannabis in chronic frequent and occasional smokers.

PubMed

Anizan, Sebastien; Milman, Garry; Desrosiers, Nathalie; Barnes, Allan J; Gorelick, David A; Huestis, Marilyn A

2013-10-01

Oral fluid (OF) is an alternative biological matrix for monitoring cannabis intake in drug testing, and drugged driving (DUID) programs, but OF cannabinoid test interpretation is challenging. Controlled cannabinoid administration studies provide a scientific database for interpreting cannabinoid OF tests. We compared differences in OF cannabinoid concentrations from 19 h before to 30 h after smoking a 6.8% THC cigarette in chronic frequent and occasional cannabis smokers. OF was collected with the Statsure Saliva Sampler™ OF device. 2D-GC-MS was used to quantify cannabinoids in 357 OF specimens; 65 had inadequate OF volume within 3 h after smoking. All OF specimens were THC-positive for up to 13.5 h after smoking, without significant differences between frequent and occasional smokers over 30 h. Cannabidiol (CBD) and cannabinol (CBN) had short median last detection times (2.5-4 h for CBD and 6-8 h for CBN) in both groups. THCCOOH was detected in 25 and 212 occasional and frequent smokers' OF samples, respectively. THCCOOH provided longer detection windows than THC in all frequent smokers. As THCCOOH is not present in cannabis smoke, its presence in OF minimizes the potential for false positive results from passive environmental smoke exposure, and can identify oral THC ingestion, while OF THC cannot. THC ≥ 1 μg/L, in addition to CBD ≥ 1 μg/L or CBN ≥ 1 μg/L suggested recent cannabis intake (≤13.5 h), important for DUID cases, whereas THC ≥ 1 μg/L or THC ≥ 2 μg/L cutoffs had longer detection windows (≥30 h), important for workplace testing. THCCOOH windows of detection for chronic, frequent cannabis smokers extended beyond 30 h, while they were shorter (0-24 h) for occasional cannabis smokers.

Passive cannabis smoke exposure and oral fluid testing.

PubMed

Niedbala, Sam; Kardos, Keith; Salamone, Sal; Fritch, Dean; Bronsgeest, Matth; Cone, Edward J

2004-10-01

Oral fluid testing for Delta(9)-tetrahydrocannabinol (THC) provides a convenient means of detection of recent cannabis usage. In this study, the risk of positive oral fluid tests from passive cannabis smoke exposure was investigated by housing four cannabis-free volunteers in a small, unventilated, and sealed room with an approximate volume of 36 m(3). Five active cannabis smokers were also present in the room, and each smoked a single cannabis cigarette (1.75% THC). Cannabis smoking occurred over the first 20 min of the study session. All subjects remained in the room for approximately 4 h. Oral fluid specimens were collected with the Intercept DOA Oral Specimen Collection Device. Three urine specimens were collected (0, 20, and 245 min). In addition, three air samples were collected for measurement of THC content. All oral fluid specimens were screened by enzyme immunoassay (EIA) for cannabinoids (cutoff concentration = 3 ng/mL) and tested by gas chromatography-tandem mass spectrometry (GC-MS-MS) for THC (LOQ/LOD = 0.75 ng/mL). All urine specimens were screened by EIA for cannabinoids (cutoff concentration = 50 ng/mL) and tested by GC-MS-MS for THCCOOH (LOQ/LOD = 1 ng/mL). Air samples were measured for THC by GC-MS (LOD = 1 ng/L). A total of eight oral fluid specimens (collected 20 to 50 min following initiation of smoking) from the four passive subjects screened and confirmed positive for THC at concentrations ranging from 3.6 to 26.4 ng/mL. Two additional specimens from one passive subject, collected at 50 and 65 min, screened negative but contained THC in concentrations of 4.2 and 1.1 ng/mL, respectively. All subsequent specimens for passive participants tested negative by EIA and GC-MS-MS for the remainder of the 4-h session. In contrast, oral fluid specimens collected from the five cannabis smokers generally screened and confirmed positive for THC throughout the session at concentrations substantially higher than observed for passive subjects. Urine specimens from active cannabis smokers also screened and confirmed positive at conventional cutoff concentrations. A biphasic pattern of decline for THC was observed in oral fluid specimens collected from cannabis smokers, whereas a linear decline was seen for passive subjects suggesting that initial oral fluid contamination is cleared rapidly and is followed by THC sequestration in the oral mucosa. It is concluded that the risk of positive oral fluid tests from passive cannabis smoke inhalation is limited to a period of approximately 30 min following exposure.

Oral fluid cannabinoids in chronic cannabis smokers during oral Δ9-tetrahydrocannabinol therapy and smoked cannabis challenge

PubMed Central

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

2014-01-01

BACKGROUND Oral Δ9-tetrahydrocannabinol (THC) is effective for attenuating cannabis withdrawal and may benefit treatment of cannabis use disorders. Oral fluid (OF) cannabinoid testing, increasing in forensic and workplace settings, could be valuable for monitoring during cannabis treatment. METHODS Eleven cannabis smokers resided on a closed research unit for 51 days, and received daily 0, 30, 60, and 120 mg oral THC in divided doses for 5 days. There was a 5-puff smoked cannabis challenge on the 5th day. Each medication session was separated by 9 days of ad libitum cannabis smoking. OF was collected the evening prior to and throughout oral THC sessions and analyzed by 2-dimensional GC-MS for THC, cannabidiol (CBD), cannabinol (CBN), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). RESULTS During all oral THC administrations, THC OF concentrations decreased to ≤78.2, 33.2, and 1.4 μg/L by 24, 48, and 72h, respectively. CBN also decreased over time with concentrations 10-fold lower than THC, with none detected beyond 69h. CBD and 11-OH-THC were rarely detected, only within 19 and 1.6h post smoking, respectively. THCCOOH OF concentrations were dose-dependent and increased over time during 120 mg THC dosing. After cannabis smoking, THC, CBN, and THCCOOH concentrations showed a significant dose-effect and decreased significantly over time. CONCLUSIONS Oral THC dosing significantly affected OF THCCOOH but minimally contributed to THC OF concentrations; prior ad libitum smoking was the primary source of THC, CBD and CBN. Higher cannabinoid concentrations following active oral THC administrations versus placebo suggest a compensatory effect of THC tolerance on smoking topography. PMID:23938457

Finding cannabinoids in hair does not prove cannabis consumption.

PubMed

Moosmann, Bjoern; Roth, Nadine; Auwärter, Volker

2015-10-07

Hair analysis for cannabinoids is extensively applied in workplace drug testing and in child protection cases, although valid data on incorporation of the main analytical targets, ∆9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-THC (THC-COOH), into human hair is widely missing. Furthermore, ∆9-tetrahydrocannabinolic acid A (THCA-A), the biogenetic precursor of THC, is found in the hair of persons who solely handled cannabis material. In the light of the serious consequences of positive test results the mechanisms of drug incorporation into hair urgently need scientific evaluation. Here we show that neither THC nor THCA-A are incorporated into human hair in relevant amounts after systemic uptake. THC-COOH, which is considered an incontestable proof of THC uptake according to the current scientific doctrine, was found in hair, but was also present in older hair segments, which already grew before the oral THC intake and in sebum/sweat samples. Our studies show that all three cannabinoids can be present in hair of non-consuming individuals because of transfer through cannabis consumers, via their hands, their sebum/sweat, or cannabis smoke. This is of concern for e.g. child-custody cases as cannabinoid findings in a child's hair may be caused by close contact to cannabis consumers rather than by inhalation of side-stream smoke.

In Vitro Stability of Free and Glucuronidated Cannabinoids in Urine Following Controlled Smoked Cannabis

PubMed Central

Desrosiers, Nathalie A.; Lee, Dayong; Scheidweiler, Karl B.; Concheiro-Guisan, Marta; Gorelick, David A.; Huestis, Marilyn A.

2014-01-01

Analyte stability is an important factor in urine test interpretation, yet cannabinoid stability data are limited. A comprehensive study of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide stabilities in authentic urine was completed. Urine samples after ad libitum cannabis smoking were pooled to prepare low and high pools for each study participant; baseline concentrations were measured within 24h at room temperature (RT), 4°C and −20°C. Stability at RT, 4°C and −20°C was evaluated by Friedman tests for up to 1 year. THCCOOH, THC-glucuronide, and THCCOOH-glucuronide were quantified in baseline pools. RT THCCOOH baseline concentrations were significantly higher than −20°C, but not 4°C baseline concentrations. After 1 week at RT, THCCOOH increased, THCCOOH-glucuronide decreased, but THC-glucuronide was unchanged. In RT low pool, total THCCOOH (THCCOOH+THCCOOH-glucuronide) was significantly lower after 1 week. At 4°C, THCCOOH was stable 2 weeks, THCCOOH-glucuronide 1 month and THC-glucuronide for at least 6 months. THCCOOH was stable frozen for 1 year, but 6 months high pool results were significantly higher than baseline; THC-glucuronide and THCCOOH-glucuronide were stable for 6 months. Total THCCOOH was stable 6 months at 4°C, and frozen 6 months (low) and 1 year (high). THC, cannabidiol and cannabinol were never detected in urine; although not detected initially, 11-OH-THC was detected in 2 low and 3 high pools after one week at RT. Substantial THCCOOH-glucuronide deconjugation was observed at RT and 4°C. Analysis should be conducted within 3 months if non-hydrolyzed THCCOOH or THCCOOH-glucuronide quantification is required. PMID:24292435

Validation of an Enzyme Immunoassay for Detection and Semiquantification of Cannabinoids in Oral Fluid

PubMed Central

Schwope, David M.; Milman, Garry; Huestis, Marilyn A.

2011-01-01

BACKGROUND Oral fluid (OF) is gaining prominence as an alternative matrix for monitoring drugs of abuse in the workplace, criminal justice, and driving under the influence of drugs programs. It is important to characterize assay performance and limitations of screening techniques for Δ9-tetrahydrocannabinol (THC) in OF. METHODS We collected OF specimens by use of the Quantisal™ OF collection device from 13 daily cannabis users after controlled oral cannabinoid administration. All specimens were tested with the Immunalysis Sweat/OF THC Direct ELISA and confirmed by 2-dimensional GC-MS. RESULTS The limit of detection was <1 µg/L THC equivalent, and the assay demonstrated linearity from 1 to 50 µg/L, with semiquantification to 200 µg/L. Intraplate imprecision (n = 7) ranged from 2.9% to 7.7% CV, and interplate imprecision (n = 20) was 3.0%–9.1%. Cross-reactivities at 4 µg/L were as follows: 11-hydroxy-THC, 198%; Δ8-tetrahydrocannabinol (Δ8-THC), 128%; 11-nor-9-carboxy-THC (THCCOOH), 121%; THC (target), 98%; cannabinol, 87%; THCCOOH-glucuronide, 11%; THC-glucuronide, 10%; and cannabidiol, 2.4%. Of 499 tested OF specimens, 52 confirmed positive (THC 2.0–290 µg/L), with 100% diagnostic sensitivity at the proposed Substance Abuse and Mental Health Services Administration screening cutoff of 4 µg/L cannabinoids and GC-MS cutoff of 2 µg/L THC. Forty-seven specimens screened positive but were not confirmed by 2D-GC-MS, yielding 89.5% diagnostic specificity and 90.6% diagnostic efficiency. Thirty-one of 47 unconfirmed immunoassay positive specimens were from 1 individual and contained >400 ng/L THCCOOH, potentially contributing to cross-reactivity. CONCLUSIONS The Immunalysis Sweat/OF THC Direct ELISA is an effective screening procedure for detecting cannabinoids in OF. PMID:20360126

A rapid culture system uninfluenced by an inoculum effect increases reliability and convenience for drug susceptibility testing of Mycobacterium tuberculosis.

PubMed

Jung, Yong-Gyun; Kim, Hyejin; Lee, Sangyeop; Kim, Suyeoun; Jo, EunJi; Kim, Eun-Geun; Choi, Jungil; Kim, Hyun Jung; Yoo, Jungheon; Lee, Hye-Jeong; Kim, Haeun; Jung, Hyunju; Ryoo, Sungweon; Kwon, Sunghoon

2018-06-05

The Disc Agarose Channel (DAC) system utilizes microfluidics and imaging technologies and is fully automated and capable of tracking single cell growth to produce Mycobacterium tuberculosis (MTB) drug susceptibility testing (DST) results within 3~7 days. In particular, this system can be easily used to perform DSTs without the fastidious preparation of the inoculum of MTB cells. Inoculum effect is one of the major problems that causes DST errors. The DAC system was not influenced by the inoculum effect and produced reliable DST results. In this system, the minimum inhibitory concentration (MIC) values of the first-line drugs were consistent regardless of inoculum sizes ranging from ~10 3 to ~10 8 CFU/mL. The consistent MIC results enabled us to determine the critical concentrations for 12 anti-tuberculosis drugs. Based on the determined critical concentrations, further DSTs were performed with 254 MTB clinical isolates without measuring an inoculum size. There were high agreement rates (96.3%) between the DAC system and the absolute concentration method using Löwenstein-Jensen medium. According to these results, the DAC system is the first DST system that is not affected by the inoculum effect. It can thus increase reliability and convenience for DST of MTB. We expect that this system will be a potential substitute for conventional DST systems.

Recovery and Stability of Δ9-Tetrahydrocannabinol Using the Oral-Eze® Oral Fluid Collection System and Intercept® Oral Specimen Collection Device.

PubMed

Samano, Kimberly L; Anne, Lakshmi; Johnson, Ted; Tang, Kenneth; Sample, R H Barry

2015-10-01

Oral fluid (OF) is increasingly used for clinical, forensic and workplace drug testing as an alternative to urine. Uncertainties surrounding OF collection device performance, drug stability and testing reproducibility may be partially responsible for delays in the implementation of OF testing in regulated drug testing programs. Stability of Δ(9)-tetrahydrocannabinol (THC) fortified and authentic specimens was examined after routine collection, transport and laboratory testing. Acceptable recovery and stability were observed when THC-fortified OF (1.5 and 4.5 ng/mL) was applied to Oral-Eze devices. Neat OF samples collected with Oral-Eze, processed per the package insert, and fortified with THC (3 and 6 ng/mL) were stable (±20%) at room temperature (21-25°C), refrigerated (2-8°C) and frozen (-25 to -15°C) conditions up to 1 month, while samples collected with Intercept devices showed decreases at refrigerated and room temperatures. After long-term refrigerated or frozen storage, maximum reductions in THC concentrations were 42% for Oral-Eze and 69% for Intercept. After ≥1 year frozen storage, 80.7% of laboratory specimens positive for THC (3 ng/mL cut-off) by GC-MS were reconfirmed positive (within 25%), with an average THC decrease of 4.2%. Specimens (n = 47) processed with Oral-Eze (diluted) and tested via enzyme immunoassay were concordant with LC-MS-MS results and showed 100% sensitivity and 95% specificity. Paired specimens collected with Oral-Eze and Intercept exhibited 98% overall agreement between the immunoassay test systems. Collectively, these data demonstrate consistent and reproducible recovery and stability of THC in OF after collection, transport and laboratory testing using the Oral-Eze OF Collection System. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

40 CFR 1066.15 - Overview of test procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Hydrocarbons, HC, which may be expressed in the following ways: (i) Total hydrocarbons, THC. (ii) Nonmethane hydrocarbons, NMHC, which results from subtracting methane, CH4, from THC. (iii) Total hydrocarbon-equivalent, THCE, which results from adjusting THC mathematically to be equivalent on a carbon-mass basis. (iv...

40 CFR 86.127-12 - Test procedures; overview.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: (1) Gaseous exhaust THC, NMHC, NMOG, CO, NOX, CO2, N2O, CH4, CH3OH, C2H5OH, C2H4O, and HCHO. (2... exhaust emission test is designed to determine gaseous THC, NMHC, NMOG, CO, CO2, CH4, NOX, N2O, and... THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, N2O, and NOX...

40 CFR 86.127-12 - Test procedures; overview.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: (1) Gaseous exhaust THC, NMHC, NMOG, CO, NOX, CO2, N2O, CH4, CH3OH, C2H5OH, C2H4O, and HCHO. (2... exhaust emission test is designed to determine gaseous THC, NMHC, NMOG, CO, CO2, CH4, NOX, N2O, and... THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, N2O, and NOX...

40 CFR 86.127-12 - Test procedures; overview.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: (1) Gaseous exhaust THC, NMHC, NMOG, CO, NOX, CO2, N2O, CH4, CH3OH, C2H5OH, C2H4O, and HCHO. (2... exhaust emission test is designed to determine gaseous THC, NMHC, NMOG, CO, CO2, CH4, NOX, N2O, and... THC using a heated sample line and analyzer; the other gaseous emissions (CH4, CO, CO2, N2O, and NOX...

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.

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.

Acquisition of Turbulence Data Using the DST Group Constant-Temperature Hot-Wire Anemometer System

DTIC Science & Technology

2015-10-01

fluctuations in the low-speed wind tunnel at DST Group. The use of both single- wire and crossed- wire (2 wire ) probes is described. Areas covered include a...fluid-flow studies, including testing of models of aircraft, ships and submarines in wind and water tunnels. Hot- wire anemometers and associated hot...spectra of velocity fluctuations in the low-speed wind tunnel at DST Group. The use of both single- wire and crossed- wire (2 wires ) probes is

Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure of the rabbit.

PubMed

ElSohly, M A; Harland, E C; Benigni, D A; Waller, C W

1984-06-01

Thirty-two different cannabinoids were tested for their ability to reduce intraocular pressure (IOP) in the rabbit. These included many of delta 9- and delta 8-THC derivatives and metabolites along with other natural and synthetic cannabinoids. In addition, some non-cannabinoid constituents of Cannabis were screened using the same model. All compounds were administered intravenously, while only a few were tested topically in mineral oil. Water soluble derivatives of delta 9- and delta 8-THC were prepared and tested topically in aqueous solution. The data revealed that certain derivatives of delta 9-and delta 8-THC were more active in lowering IOP than the parent cannabinoids. In addition, compounds other than delta 9- and delta 8-THC and their derivatives were shown to have activity.

40 CFR 63.9320 - What procedures must I use?

Code of Federal Regulations, 2014 CFR

2014-07-01

... the carbon monoxide (CO) or total hydrocarbon (THC) concentration limitation consists of the first 4-hour rolling average CO or THC concentration recorded after completion of the CEMS performance evaluation. You must correct the CO or THC concentration at the outlet of the engine test cell/stand or the...

40 CFR Table 4 to Subpart Zzzz of... - Requirements for Performance Tests

Code of Federal Regulations, 2013 CFR

2013-07-01

... determine O2 concentration must be made at the same time as the measurements for formaldehyde or THC... formaldehyde or THC concentration. iv. If demonstrating compliance with the formaldehyde percent reduction...-hour or longer runs. v. If demonstrating compliance with the THC percent reduction requirement, measure...

40 CFR 63.9320 - What procedures must I use?

Code of Federal Regulations, 2011 CFR

2011-07-01

... the carbon monoxide (CO) or total hydrocarbon (THC) concentration limitation consists of the first 4-hour rolling average CO or THC concentration recorded after completion of the CEMS performance evaluation. You must correct the CO or THC concentration at the outlet of the engine test cell/stand or the...

40 CFR 63.9320 - What procedures must I use?

Code of Federal Regulations, 2012 CFR

2012-07-01

... the carbon monoxide (CO) or total hydrocarbon (THC) concentration limitation consists of the first 4-hour rolling average CO or THC concentration recorded after completion of the CEMS performance evaluation. You must correct the CO or THC concentration at the outlet of the engine test cell/stand or the...

40 CFR 63.9320 - What procedures must I use?

Code of Federal Regulations, 2013 CFR

2013-07-01

... the carbon monoxide (CO) or total hydrocarbon (THC) concentration limitation consists of the first 4-hour rolling average CO or THC concentration recorded after completion of the CEMS performance evaluation. You must correct the CO or THC concentration at the outlet of the engine test cell/stand or the...

40 CFR 86.237-08 - Dynamometer test run, gaseous emissions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... temperature recorder, the vehicle cooling fan, and the heated THC analysis recorder (diesel-cycle only). (The heat exchanger of the constant volume sampler, if used, petroleum-fueled diesel-cycle THC analyzer continuous sample line and filter, methanol-fueled vehicle THC, methanol and formaldehyde sample lines, if...

40 CFR Table 4 to Subpart Zzzz of... - Requirements for Performance Tests

Code of Federal Regulations, 2014 CFR

2014-07-01

... determine O2 concentration must be made at the same time as the measurements for formaldehyde or THC... formaldehyde or THC concentration. iv. If demonstrating compliance with the formaldehyde percent reduction...-hour or longer runs. v. If demonstrating compliance with the THC percent reduction requirement, measure...

40 CFR 63.9320 - What procedures must I use?

Code of Federal Regulations, 2010 CFR

2010-07-01

... the carbon monoxide (CO) or total hydrocarbon (THC) concentration limitation consists of the first 4-hour rolling average CO or THC concentration recorded after completion of the CEMS performance evaluation. You must correct the CO or THC concentration at the outlet of the engine test cell/stand or the...

40 CFR 86.237-08 - Dynamometer test run, gaseous emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... temperature recorder, the vehicle cooling fan, and the heated THC analysis recorder (diesel-cycle only). (The heat exchanger of the constant volume sampler, if used, petroleum-fueled diesel-cycle THC analyzer continuous sample line and filter, methanol-fueled vehicle THC, methanol and formaldehyde sample lines, if...

Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats

PubMed Central

Wakley, Alexa A; Wiley, Jenny L; Craft, Rebecca M

2015-01-01

The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones. Rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX). GDX females received no hormone replacement (GDX+0), estradiol (GDX+E2), progesterone (GDX+P4), or both (GDX+E2/P4). GDX male rats received no hormone (GDX+0) or testosterone (GDX+T). Two weeks later, antinociceptive potency of THC was determined (pre-chronic test) on the warm water tail withdrawal and paw pressure assays. Vehicle or a sex-specific THC dose (females, 5.7 mg/kg, males, 9.9 mg/kg) was administered twice-daily for 9 days, then the THC dose-effect curves were re-determined (post-chronic test). On the pre-chronic test (both assays), THC was more potent in sham-GDX females than males, and gonadectomy did not alter this sex difference. In GDX females, P4 significantly decreased THC’s antinociceptive potency, whereas E2 had no effect. In GDX males, T did not alter THC’s antinociceptive potency. After chronic THC treatment, THC’s antinociceptive potency was decreased more in sham-GDX females than males, on the tail withdrawal test; this sex difference in tolerance was not altered in GDX or hormone-treated groups. These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones. PMID:25863271

Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment.

PubMed

Murphy, Michelle; Mills, Sierra; Winstone, Joanna; Leishman, Emma; Wager-Miller, Jim; Bradshaw, Heather; Mackie, Ken

2017-01-01

Introduction: The high prevalence of adolescent cannabis use, the association between this use and later psychiatric disease, and increased access to high-potency cannabis highlight the need for a better understanding of the long-term effects of adolescent cannabis use on cognitive and behavioral outcomes. Furthermore, increasing Δ 9 -tetrahydrocannabinol (THC) in high-potency cannabis is accompanied by a decrease in cannabidiol (CBD), thus an understanding of the interactions between CBD and THC in the neurodevelopmental effects of THC is also important. The current study examined the immediate and long-term behavioral consequences of THC, CBD, and their combination in a mouse model of adolescent cannabis use. Materials and Methods: Male CD1 mice received daily injections of THC (3 mg/kg), CBD (3 mg/kg), CBD+THC (3 mg/kg each), vehicle, or remained undisturbed in their home cage (no handling/injections), either during adolescence (postnatal day [PND] 28-48) or during early adulthood (PND 69-89). Animals were then evaluated with a battery of behavioral tests 1 day after drug treatment, and again after 42 drug-free days. The tests included the following: open field (day 1), novel object recognition (NOR; day 2), marble burying (day 3), elevated plus maze (EPM; day 4), and Nestlet shredding (day 5). Results: Chronic administration of THC during adolescence led to immediate and long-term impairments in object recognition/working memory, as measured by the NOR task. In contrast, adult administration of THC caused immediate, but not long term, impairment of object/working memory. Adolescent chronic exposure to THC increased repetitive and compulsive-like behaviors, as measured by the Nestlet shredding task. Chronic administration of THC, either during adolescence or during adulthood, led to a delayed increase in anxiety as measured by the EPM. All THC-induced behavioral abnormalities were prevented by the coadministration of CBD+THC, whereas CBD alone did not influence behavioral outcomes. Conclusion: These data suggest that chronic exposure to THC during adolescence leads to some of the behavioral abnormalities common in schizophrenia. Interestingly, CBD appeared to antagonize all THC-induced behavioral abnormalities. These findings support the hypothesis that adolescent THC use can impart long-term behavioral deficits; however, cotreatment with CBD prevents these deficits.

Chronic Adolescent Δ9-Tetrahydrocannabinol Treatment of Male Mice Leads to Long-Term Cognitive and Behavioral Dysfunction, Which Are Prevented by Concurrent Cannabidiol Treatment

PubMed Central

Murphy, Michelle; Mills, Sierra; Winstone, Joanna; Leishman, Emma; Wager-Miller, Jim; Bradshaw, Heather; Mackie, Ken

2017-01-01

Abstract Introduction: The high prevalence of adolescent cannabis use, the association between this use and later psychiatric disease, and increased access to high-potency cannabis highlight the need for a better understanding of the long-term effects of adolescent cannabis use on cognitive and behavioral outcomes. Furthermore, increasing Δ9-tetrahydrocannabinol (THC) in high-potency cannabis is accompanied by a decrease in cannabidiol (CBD), thus an understanding of the interactions between CBD and THC in the neurodevelopmental effects of THC is also important. The current study examined the immediate and long-term behavioral consequences of THC, CBD, and their combination in a mouse model of adolescent cannabis use. Materials and Methods: Male CD1 mice received daily injections of THC (3 mg/kg), CBD (3 mg/kg), CBD+THC (3 mg/kg each), vehicle, or remained undisturbed in their home cage (no handling/injections), either during adolescence (postnatal day [PND] 28–48) or during early adulthood (PND 69–89). Animals were then evaluated with a battery of behavioral tests 1 day after drug treatment, and again after 42 drug-free days. The tests included the following: open field (day 1), novel object recognition (NOR; day 2), marble burying (day 3), elevated plus maze (EPM; day 4), and Nestlet shredding (day 5). Results: Chronic administration of THC during adolescence led to immediate and long-term impairments in object recognition/working memory, as measured by the NOR task. In contrast, adult administration of THC caused immediate, but not long term, impairment of object/working memory. Adolescent chronic exposure to THC increased repetitive and compulsive-like behaviors, as measured by the Nestlet shredding task. Chronic administration of THC, either during adolescence or during adulthood, led to a delayed increase in anxiety as measured by the EPM. All THC-induced behavioral abnormalities were prevented by the coadministration of CBD+THC, whereas CBD alone did not influence behavioral outcomes. Conclusion: These data suggest that chronic exposure to THC during adolescence leads to some of the behavioral abnormalities common in schizophrenia. Interestingly, CBD appeared to antagonize all THC-induced behavioral abnormalities. These findings support the hypothesis that adolescent THC use can impart long-term behavioral deficits; however, cotreatment with CBD prevents these deficits. PMID:29098186

40 CFR 80.60 - Test fleet requirements for exhaust emission testing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... vehicle with an exhaust total hydrocarbon (THC) emissions rate which is less than or equal to twice the... THC emissions rate which is greater than two times the applicable emissions standard shall be placed...

40 CFR 80.60 - Test fleet requirements for exhaust emission testing.

Code of Federal Regulations, 2011 CFR

2011-07-01

... vehicle with an exhaust total hydrocarbon (THC) emissions rate which is less than or equal to twice the... THC emissions rate which is greater than two times the applicable emissions standard shall be placed...

40 CFR 80.60 - Test fleet requirements for exhaust emission testing.

Code of Federal Regulations, 2014 CFR

2014-07-01

... vehicle with an exhaust total hydrocarbon (THC) emissions rate which is less than or equal to twice the... THC emissions rate which is greater than two times the applicable emissions standard shall be placed...

40 CFR 80.60 - Test fleet requirements for exhaust emission testing.

Code of Federal Regulations, 2012 CFR

2012-07-01

... vehicle with an exhaust total hydrocarbon (THC) emissions rate which is less than or equal to twice the... THC emissions rate which is greater than two times the applicable emissions standard shall be placed...

40 CFR 80.60 - Test fleet requirements for exhaust emission testing.

Code of Federal Regulations, 2013 CFR

2013-07-01

... vehicle with an exhaust total hydrocarbon (THC) emissions rate which is less than or equal to twice the... THC emissions rate which is greater than two times the applicable emissions standard shall be placed...

qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients

PubMed Central

Goulart, Luiz Ricardo; Truman, Richard W.; Goulart, Isabela Maria B.; Vissa, Varalakshmi; Li, Wei; Matsuoka, Masanori; Suffys, Philip; Fontes, Amanda B.; Rosa, Patricia S.; Scollard, David M.; Williams, Diana L.

2017-01-01

Background Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. Methodology/Principal findings The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite’s stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite’s stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing. Conclusion/Significance Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy. PMID:28570560

Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: A pilot study.

PubMed

Swords, Ronan T; Azzam, Diana; Al-Ali, Hassan; Lohse, Ines; Volmar, Claude-Henry; Watts, Justin M; Perez, Aymee; Rodriguez, Ana; Vargas, Fernando; Elias, Roy; Vega, Francisco; Zelent, Arthur; Brothers, Shaun P; Abbasi, Taher; Trent, Jonathan; Rangwala, Shaukat; Deutsch, Yehuda; Conneally, Eibhlin; Drusbosky, Leylah; Cogle, Christopher R; Wahlestedt, Claes

2018-01-01

A precision medicine approach is appealing for use in AML due to ease of access to tumor samples and the significant variability in the patients' response to treatment. Attempts to establish a precision medicine platform for AML, however, have been unsuccessful, at least in part due to the use of small compound panels and having relatively slow turn over rates, which restricts the scope of treatment and delays its onset. For this pilot study, we evaluated a cohort of 12 patients with refractory AML using an ex vivo drug sensitivity testing (DST) platform. Purified AML blasts were screened with a panel of 215 FDA-approved compounds and treatment response was evaluated after 72h of exposure. Drug sensitivity scoring was reported to the treating physician, and patients were then treated with either DST- or non-DST guided therapy. We observed survival benefit of DST-guided therapy as compared to the survival of patients treated according to physician recommendation. Three out of four DST-treated patients displayed treatment response, while all of the non-DST-guided patients progressed during treatment. DST rapidly and effectively provides personalized treatment recommendations for patients with refractory AML. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

40 CFR Table 2 to Subpart Dddd of... - Operating Requirements

Code of Federal Regulations, 2011 CFR

2011-07-01

... minimum temperature established during the performance test Maintain the 3-hour block average THC... representative sample of the catalyst at least every 12 months Maintain the 3-hour block average THC... established according to § 63.2262(m) Maintain the 24-hour block average THC concentration a in the biofilter...

40 CFR Table 2 to Subpart Dddd of... - Operating Requirements

Code of Federal Regulations, 2010 CFR

2010-07-01

... minimum temperature established during the performance test Maintain the 3-hour block average THC... representative sample of the catalyst at least every 12 months Maintain the 3-hour block average THC... established according to § 63.2262(m) Maintain the 24-hour block average THC concentration a in the biofilter...

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.

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

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography-Tandem Mass Spectrometry.

PubMed

Andrenyak, David M; Moody, David E; Slawson, Matthew H; O'Leary, Daniel S; Haney, Margaret

2017-05-01

Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5-500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at -20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography–Tandem Mass Spectrometry

PubMed Central

Andrenyak, David M.; Slawson, Matthew H.; O'Leary, Daniel S.; Haney, Margaret

2017-01-01

Abstract Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography–tandem mass spectrometry (GC–MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5–500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid–liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at −20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range. PMID:28069869

HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

PubMed

Jokinen, Jussi; Nordström, Peter

2008-11-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

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).

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Δ9-tetrahydrocannabinol

PubMed Central

Vann, Robert E.; Gamage, Thomas F.; Warner, Jonathan A.; Marshall, Ericka M.; Taylor, Nathan L.; Martin, Billy R.; Wiley, Jenny L.

2008-01-01

Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Δ9-tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC’s effects by these other cannabinoids [e.g., cannabidiol (CBD)] has been stimulated anew by recent approval by Canada of Sativex (a 1:1 dose ratio combination of CBD:THC) for the treatment of multiple sclerosis. The goal of this study was to determine the degree to which THC’s abuse-related effects were altered by co-administration of CBD. To this end, CBD and THC were assessed alone and in combination in a two-lever THC discrimination procedure in Long-Evans rats and in a conditioned place preference/aversion (CPP/A) model in ICR mice. CBD did not alter the discriminative stimulus effects of THC at any CBD:THC dose ratio tested. In contrast, CBD, at CBD:THC dose ratios of 1:1 and 1:10, reversed CPA produced by acute injection with 10 mg/kg THC. When administered alone, CBD did not produce effects in either procedure. These results suggest that CBD, when administered with THC at therapeutically relevant ratios, may ameliorate aversive effects (e.g., dysphoria) often associated with initial use of THC alone. While this effect may be beneficial for therapeutic usage of a CBD:THC combination medication, our discrimination results showing that CBD did not alter THC’s discriminative stimulus effects suggest that CBD:THC combination medications may also produce THC-like subjective effects at these dose ratios. PMID:18206320

Obstructive sleep apnea syndrome causes a pseudo-Cushing's state in Japanese obese patients with type 2 diabetes mellitus.

PubMed

Tamada, Daisuke; Otsuki, Michio; Kashine, Susumu; Hirata, Ayumu; Onodera, Toshiharu; Kitamura, Tetsuhiro; Shimomura, Iichiro

2013-01-01

Activation of the hypothalamic-pituitary-adrenal axis has been reported in some patients with the obstructive sleep apnea syndrome (OSAS). In current study, we investigated whether OSAS affect the screening test for subclinical Cushing's disease using 0.5 mg overnight dexamethasone suppression test (DST) in Japanese obese diabetic patients with OSAS. Among Japanese obese patients with type 2 diabetes mellitus who had been hospitalized in our department, we selected 20 patients with moderate to severe untreated OSAS (apnea-hypoxia index, AHI, of ≥15 events/hour). All patients underwent 0.5 mg DST. The same test was repeated in patients with positive response of it within a few days after continuous positive airway pressure (CPAP) therapy. We found that five patients showed positive response of DST (25%). Three of these patients continued to use CPAP, and they showed normal response of DST after CPAP therapy. Serum cortisol after 0.5 mg DST measured before CPAP therapy correlated significantly with fasting serum cortisol level (r=0.764, p<0.0001), but not with various clinical parameters, including AHI (p=0.784), body mass index (p=0.984), waist circumference (p=0.957), HbA1c (p=0.261), fasting plasma glucose (p=0.420) and HOMA-IR (p=0.500). Our study show that OSAS causes a pseudo-Cushing's syndrome in obese patients with type 2 diabetes mellitus, which phenomena can be reversed by CPAP therapy.

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 and human cannabinoid studies may be related to pharmacokinetic differences associated with route of administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Screening for subclinical Cushing's syndrome in type 2 diabetes mellitus: low false-positive rates with nocturnal salivary cortisol.

PubMed

Gagliardi, L; Chapman, I M; O'Loughlin, P; Torpy, D J

2010-04-01

The diagnosis of subclinical Cushing's syndrome (SCS) is important, but its relative rarity amongst patients with common metabolic disorders requires a simple test with a low false-positive rate. Using nocturnal salivary cortisol (NSC), which we first validated in patients with suspected and proven Cushing's syndrome, we screened 106 overweight patients with type 2 diabetes mellitus, a group at high risk of SCS and nontumoral hypothalamic-pituitary-adrenal axis perturbations. Our hypothesis was that a lower false-positive rate with NSC was likely, compared with that reported with the dexamethasone suppression test (DST) (10-20%), currently the foundation of diagnosis of SCS. No participant had clinically apparent Cushing's syndrome. Three participants had an elevated NSC but further testing excluded SCS. In this study, NSC had a lower false-positive rate (3%) than previously reported for the DST. Given the reported excellent performance of NSC in detection of hypercortisolism, the low false-positive rate in SCS suggests NSC may be superior to the DST for SCS screening. The NSC and DST should be compared directly in metabolic disorder patients; although our data suggest the patient group will need to be substantially larger to definitively determine the optimal screening test. Georg Thieme Verlag KG Stuttgart New York.

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

PubMed

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

2013-08-01

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

International Space Station Environmental Control and Life Support System Acceptance Testing for Node 1 Temperature and Humidity Control Subsystem

NASA Technical Reports Server (NTRS)

Williams, David E.

2011-01-01

The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Storage (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper will provide a summary of the Node 1 ECLS THC subsystem design and a detailed discussion of the ISS ECLS Acceptance Testing methodology utilized for this subsystem.The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Storage (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper will provide a summary of the Node 1 ECLS THC subsystem design and a detailed discussion of the ISS ECLS Acceptance Testing methodology utilized for this subsystem.

Effects of cognitive-motor dual-task training combined with auditory motor synchronization training on cognitive functioning in individuals with chronic stroke: A pilot randomized controlled trial.

PubMed

Park, Myoung-Ok; Lee, Sang-Heon

2018-06-01

Preservation and enhancement of cognitive function are essential for the restoration of functional abilities and independence following stroke. While cognitive-motor dual-task training (CMDT) has been utilized in rehabilitation settings, many patients with stroke experience impairments in cognitive function that can interfere with dual-task performance. In the present study, we investigated the effects of CMDT combined with auditory motor synchronization training (AMST) utilizing rhythmic cues on cognitive function in patients with stroke. The present randomized controlled trial was conducted at a single rehabilitation hospital. Thirty patients with chronic stroke were randomly divided an experimental group (n = 15) and a control group (n = 15). The experimental group received 3 CMDT + AMST sessions per week for 6 weeks, whereas the control group received CMDT only 3 times per week for 6 weeks. Changes in cognitive function were evaluated using the trail making test (TMT), digit span test (DST), and stroop test (ST). Significant differences in TMT-A and B (P = .001, P = .001), DST-forward (P = .001, P = .001), DST-backward (P = .000, P = .001), ST-word (P = .001, P = .001), and ST-color (P = .002, P = .001) scores were observed in both the control and experimental groups, respectively. Significant differences in TMT-A (P = .001), DST-forward (P = .027), DST-backward (P = .002), and ST-word (P = .025) scores were observed between the 2 groups. Performance speed on the TMT-A was faster in the CMDT + AMST group than in the CMDT group. Moreover, DST-forward and DST-backward scores were higher in the CMDT + AMST group than in the CDMT group. Although ST-color results were similar in the 2 groups, ST-word scores were higher in the CMDT + AMST group than in the CMDT group. This finding indicates that the combined therapy CMDT and AMST can be used to increase attention, memory, and executive function for people with stroke.

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

PubMed

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

2015-12-01

Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

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.

40 CFR 86.159-08 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... gasoline-fueled Otto-cycle vehicles, the composite samples collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2...

40 CFR 86.160-00 - Exhaust emission test procedure for SC03 emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All...

40 CFR 86.160-00 - Exhaust emission test procedure for SC03 emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All...

40 CFR 86.159-08 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... gasoline-fueled Otto-cycle vehicles, the composite samples collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2...

40 CFR 86.159-08 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... gasoline-fueled Otto-cycle vehicles, the composite samples collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2...

40 CFR 86.159-08 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... gasoline-fueled Otto-cycle vehicles, the composite samples collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2...

40 CFR Table 5 to Subpart Zzzz of... - Initial Compliance With Emission Limitations, Operating Limitations, and Other Requirements

Code of Federal Regulations, 2014 CFR

2014-07-01

... average reduction of emissions of THC determined from the initial performance test is equal to or greater... greater than the required formaldehyde percent reduction or the average reduction of emissions of THC... average reduction of emissions of THC is 30 percent or more; ii. You have installed a CPMS to continuously...

40 CFR Table 5 to Subpart Zzzz of... - Initial Compliance With Emission Limitations, Operating Limitations, and Other Requirements

Code of Federal Regulations, 2013 CFR

2013-07-01

... average reduction of emissions of THC determined from the initial performance test is equal to or greater... greater than the required formaldehyde percent reduction or the average reduction of emissions of THC... average reduction of emissions of THC is 30 percent or more; ii. You have installed a CPMS to continuously...

40 CFR 86.160-00 - Exhaust emission test procedure for SC03 emissions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2, CH4, and NOX. (b) Dynamometer activities. (1) All...

40 CFR 86.159-08 - Exhaust emission test procedures for US06 emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... gasoline-fueled Otto-cycle vehicles, the composite samples collected in bags are analyzed for THC, CO, CO2, CH4, and NOX. For petroleum-fueled diesel-cycle vehicles, THC is sampled and analyzed continuously according to the provisions of § 86.110. Parallel bag samples of dilution air are analyzed for THC, CO, CO2...

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

PubMed

Lopez-Cepero, M; Friedman, M; Klein, T; Friedman, H

1986-06-01

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

Enzymatic Degradation of Aromatic and Aliphatic Polyesters by P. pastoris Expressed Cutinase 1 from Thermobifida cellulosilytica

PubMed Central

Gamerith, Caroline; Vastano, Marco; Ghorbanpour, Sahar M.; Zitzenbacher, Sabine; Ribitsch, Doris; Zumstein, Michael T.; Sander, Michael; Herrero Acero, Enrique; Pellis, Alessandro; Guebitz, Georg M.

2017-01-01

To study hydrolysis of aromatic and aliphatic polyesters cutinase 1 from Thermobifida cellulosilytica (Thc_Cut1) was expressed in P. pastoris. No significant differences between the expression of native Thc_Cut1 and of two glycosylation site knock out mutants (Thc_Cut1_koAsn and Thc_Cut1_koST) concerning the total extracellular protein concentration and volumetric activity were observed. Hydrolysis of poly(ethylene terephthalate) (PET) was shown for all three enzymes based on quantification of released products by HPLC and similar concentrations of released terephthalic acid (TPA) and mono(2-hydroxyethyl) terephthalate (MHET) were detected for all enzymes. Both tested aliphatic polyesters poly(butylene succinate) (PBS) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were hydrolyzed by Thc_Cut1 and Thc_Cut1_koST, although PBS was hydrolyzed to significantly higher extent than PHBV. These findings were also confirmed via quartz crystal microbalance (QCM) analysis; for PHBV only a small mass change was observed while the mass of PBS thin films decreased by 93% upon enzymatic hydrolysis with Thc_Cut1. Although both enzymes led to similar concentrations of released products upon hydrolysis of PET and PHBV, Thc_Cut1_koST was found to be significantly more active on PBS than the native Thc_Cut1. Hydrolysis of PBS films by Thc_Cut1 and Thc_Cut1_koST was followed by weight loss and scanning electron microscopy (SEM). Within 96 h of hydrolysis up to 92 and 41% of weight loss were detected with Thc_Cut1_koST and Thc_Cut1, respectively. Furthermore, SEM characterization of PBS films clearly showed that enzyme tretment resulted in morphological changes of the film surface. PMID:28596765

Identification of Recent Cannabis Use: Whole-Blood and Plasma Free and Glucuronidated Cannabinoid Pharmacokinetics following Controlled Smoked Cannabis Administration

PubMed Central

Schwope, David M.; Karschner, Erin L.; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

BACKGROUND Δ9-Tetrahydrocannabinol (THC) is the most frequently observed illicit drug in investigations of accidents and driving under the influence of drugs. THC-glucuronide has been suggested as a marker of recent cannabis use, but there are no blood data following controlled THC administration to test this hypothesis. Furthermore, there are no studies directly examining whole-blood cannabinoid pharmacokinetics, although this matrix is often the only available specimen. METHODS Participants (9 men, 1 woman) resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. We quantified THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide directly in whole blood and plasma by liquid chromatography/ tandem mass spectrometry within 24 h of collection to obviate stability issues. RESULTS Median whole blood (plasma) observed maximum concentrations (Cmax) were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) μg/L 0.25 h after starting smoking for THC, 11-OH-THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THC-glucuronide. At observed Cmax, whole-blood (plasma) detection rates were 60% (80%), 80% (90%), and 50% (80%) for CBD, CBN, and THC-glucuronide, respectively. CBD and CBN were not detectable after 1 h in either matrix (LOQ 1.0 μg/L). CONCLUSIONS Human whole-blood cannabinoid data following cannabis smoking will assist whole blood and plasma cannabinoid interpretation, while furthering identification of recent cannabis intake. PMID:21836075

Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers.

PubMed

Haney, Margaret

2007-06-01

In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of Delta(9)-tetrahydrocannabinol (THC), while in human marijuana smokers, naltrexone (50 mg) enhances the reinforcing and subjective effects of THC. The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0-40 mg) or methadone (0-10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history.

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

Viscoelastic properties of soft gels: comparison of magnetic resonance elastography and dynamic shear testing in the shear wave regime

NASA Astrophysics Data System (ADS)

Okamoto, R. J.; Clayton, E. H.; Bayly, P. V.

2011-10-01

Magnetic resonance elastography (MRE) is used to quantify the viscoelastic shear modulus, G*, of human and animal tissues. Previously, values of G* determined by MRE have been compared to values from mechanical tests performed at lower frequencies. In this study, a novel dynamic shear test (DST) was used to measure G* of a tissue-mimicking material at higher frequencies for direct comparison to MRE. A closed-form solution, including inertial effects, was used to extract G* values from DST data obtained between 20 and 200 Hz. MRE was performed using cylindrical 'phantoms' of the same material in an overlapping frequency range of 100-400 Hz. Axial vibrations of a central rod caused radially propagating shear waves in the phantom. Displacement fields were fit to a viscoelastic form of Navier's equation using a total least-squares approach to obtain local estimates of G*. DST estimates of the storage G' (Re[G*]) and loss modulus G'' (Im[G*]) for the tissue-mimicking material increased with frequency from 0.86 to 0.97 kPa (20-200 Hz, n = 16), while MRE estimates of G' increased from 1.06 to 1.15 kPa (100-400 Hz, n = 6). The loss factor (Im[G*]/Re[G*]) also increased with frequency for both test methods: 0.06-0.14 (20-200 Hz, DST) and 0.11-0.23 (100-400 Hz, MRE). Close agreement between MRE and DST results at overlapping frequencies indicates that G* can be locally estimated with MRE over a wide frequency range. Low signal-to-noise ratio, long shear wavelengths and boundary effects were found to increase residual fitting error, reinforcing the use of an error metric to assess confidence in local parameter estimates obtained by MRE.

Microbial sensor for drug susceptibility testing of Mycobacterium tuberculosis.

PubMed

Zhang, Z-T; Wang, D-B; Li, C-Y; Deng, J-Y; Zhang, J-B; Bi, L-J; Zhang, X-E

2018-01-01

Drug susceptibility testing (DST) of clinical isolates of Mycobacterium tuberculosis is critical in treating tuberculosis. We demonstrate the possibility of using a microbial sensor to perform DST of M. tuberculosis and shorten the time required for DST. The sensor is made of an oxygen electrode with M. tuberculosis cells attached to its surface. This sensor monitors the residual oxygen consumption of M. tuberculosis cells after treatment with anti-TB drugs with glycerine as a carbon source. In principle, after drug pretreatment for 4-5 days, the response differences between the sensors made of drug-sensitive isolates are distinguishable from the sensors made of drug-resistant isolates. The susceptibility of the M. tuberculosis H37Ra strain, its mutants and 35 clinical isolates to six common anti-TB drugs: rifampicin, isoniazid, streptomycin, ethambutol, levofloxacin and para-aminosalicylic acid were tested using the proposed method. The results agreed well with the gold standard method (LJ) and were determined in significantly less time. The whole procedure takes approximately 11 days and therefore has the potential to inform clinical decisions. To our knowledge, this is the first study that demonstrates the possible application of a dissolved oxygen electrode-based microbial sensor in M. tuberculosis drug resistance testing. This study used the microbial sensor to perform DST of M. tuberculosis and shorten the time required for DST. The overall detection result of the microbial sensor agreed well with that of the conventional LJ proportion method and takes less time than the existing phenotypic methods. In future studies, we will build an O 2 electrode array microbial sensor reactor to enable a high-throughput drug resistance analysis. © 2017 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

Viscoelastic properties of soft gels: comparison of magnetic resonance elastography and dynamic shear testing in the shear wave regime.

PubMed

Okamoto, R J; Clayton, E H; Bayly, P V

2011-10-07

Magnetic resonance elastography (MRE) is used to quantify the viscoelastic shear modulus, G*, of human and animal tissues. Previously, values of G* determined by MRE have been compared to values from mechanical tests performed at lower frequencies. In this study, a novel dynamic shear test (DST) was used to measure G* of a tissue-mimicking material at higher frequencies for direct comparison to MRE. A closed-form solution, including inertial effects, was used to extract G* values from DST data obtained between 20 and 200 Hz. MRE was performed using cylindrical 'phantoms' of the same material in an overlapping frequency range of 100-400 Hz. Axial vibrations of a central rod caused radially propagating shear waves in the phantom. Displacement fields were fit to a viscoelastic form of Navier's equation using a total least-squares approach to obtain local estimates of G*. DST estimates of the storage G' (Re[G*]) and loss modulus G″ (Im[G*]) for the tissue-mimicking material increased with frequency from 0.86 to 0.97 kPa (20-200 Hz, n = 16), while MRE estimates of G' increased from 1.06 to 1.15 kPa (100-400 Hz, n = 6). The loss factor (Im[G*]/Re[G*]) also increased with frequency for both test methods: 0.06-0.14 (20-200 Hz, DST) and 0.11-0.23 (100-400 Hz, MRE). Close agreement between MRE and DST results at overlapping frequencies indicates that G* can be locally estimated with MRE over a wide frequency range. Low signal-to-noise ratio, long shear wavelengths and boundary effects were found to increase residual fitting error, reinforcing the use of an error metric to assess confidence in local parameter estimates obtained by MRE.

Simultaneous Quantification of Free and Glucuronidated Cannabinoids in Human Urine by Liquid Chromatography-Tandem Mass Spectrometry

PubMed Central

Scheidweiler, Karl B.; Desrosiers, Nathalie A.; Huestis, Marilyn A.

2012-01-01

Background Cannabis is the most commonly abused drug of abuse and is commonly quantified during urine drug testing. We conducted a controlled drug administration studies investigating efficacy of urinary cannabinoid glucuronide metabolites for documenting recency of cannabis intake and for determining stability of urinary cannabinoids. Methods A liquid chromatography tandem mass spectrometry method was developed and validated quantifying Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide and THCCOOH-glucuronide in 0.5 ml human urine via supported-liquid extraction. Chromatography was performed on an Ultra Biphenyl column with a gradient of 10 mmol/l ammonium acetate, pH 6.15 and 15% methanol in acetonitrile at 0. 4ml/min. Analytes were monitored by positive and negative mode electrospray ionization and multiple reaction monitoring mass spectrometry. Results Linear ranges were 0.5–50 ng/ml for THC-glucuronide, 1–100 ng/ml for THCCOOH, 11-OH-THC and cannabidiol, 2–100 ng/ml for THC and cannabinol, and 5–500 ng/ml for THCCOOH-glucuronide (R2>0.99). Mean extraction efficiencies were 34–73% with analytical recovery (bias) 80.5–118.0% and total imprecision 3.0–10.2% coefficient of variation. Conclusion This method simultaneously quantifies urinary cannabinoids and phase II glucuronide metabolites, and enables evaluation of urinary cannabinoid glucuronides for documenting recency of cannabis intake and cannabinoid stability. The assay is applicable for routine urine cannabinoid testing. PMID:22771478

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

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.

Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses angiogenesis by targeting HIF-1α and autophagy in human osteosarcoma

PubMed Central

Zhang, Yan; Liu, Ying; Zou, Jilong; Yan, Lixin; Du, Wei; Zhang, Yafeng; Sun, Hanliang; Lu, Peng; Geng, Shuo; Gu, Rui; Zhang, Hongyue; Bi, Zhenggang

2017-01-01

Human osteosarcoma is considered a malignant tumor with poor prognosis that readily metastasizes. Tetrahydrocurcumin (THC) has been reported to have anti-tumor activity in numerous tumors. In addition, hypoxia-inducible factor-1α (HIF-1α) has been demonstrated to be associated with tumor metastasis by regulating epithelial-mesenchymal transition (EMT). However, the role of THC in osteosarcoma remains uncertain. Therefore, this study aimed to elucidate the potential mechanisms. We found that THC significantly reduced the growth of osteosarcoma cells and suppressed migration and invasion, as tested in a nude mouse lung metastasis model. Additionally, the mesenchymal-epithelial transition (MET) process was facilitated by THC. Mechanistically, our study showed that HIF-1α had a pivotal role in the anti-metastatic effect of THC. Importantly, HIF-1α expression was downregulated by THC by inhibiting Akt/mTOR and p38 MAPK pathways. Moreover, THC exhibited a remarkable inhibitory effect on HIF-1α expression and angiogenesis under hypoxic conditions. Furthermore, THC activated autophagy and induced MET and suppressed angiogenesis in a HIF-1α-related manner. Taken together, our findings suggest that THC suppresses metastasis and invasion and this may be associated with HIF-1α and autophagy, which would potentially provide therapeutic strategies for human osteosarcoma. PMID:29207631

Suppressive effect of delta 9-tetrahydrocannabinol in vitro on phagocytosis by murine macrophages.

PubMed

Friedman, M; Cepero, M L; Klein, T; Friedman, H

1986-06-01

Incubation of normal mouse peritoneal cells consisting of over 90% phagocytizing macrophages with delta 9-tetrahydrocannabinol (THC) resulted in a inhibition of phagocytic function. The THC in a dose-related manner suppressed the percentage of macrophages per culture which ingested yeast and the average number of yeast particles ingested by the phagocytizing macrophages. The vehicle used to suspend the THC in vitro, i.e., DMSO, had no detectable effect on macrophage function. Suppression of phagocytosis with no effects on viability or cell number occurred with doses of 10 micrograms or less THC per milliliter culture medium. Measurable suppression also occurred after 24- to 48-hr treatment of the macrophages with the THC. This compound had little if any detectable effect on phagocytosis when added directly to the cultures shortly before testing for phagocytosis. Further studies concerning the effects of THC on macrophage function appear warranted.

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

Dobson space telescope: development of an optical payload of the next generation

NASA Astrophysics Data System (ADS)

Segert, Tom; Danziger, Björn; Gork, Daniel; Lieder, Matthias

2017-11-01

The Dobson Space Telescope (DST) is a research project of the Department of Astronautics at the TUBerlin. For Development and commercialisation there is a close cooperation with the network of the Berlin Space Industry (RIBB). Major Partner is the Astro- und Feinwerktechnik Adlershof GmbH a specialist for space structures and head of the industry consortia which built the DLR BIRD micro satellite. The aim of the project is to develop a new type of deployable telescope that can overcome the mass and volume limitations of small satellites. With the DST payload micro satellites of the 100kg class will be able to carry 50cm main mirror diameter optics (→ 1m GSD). Basis of this technology is the fact that a telescope is mainly empty space between the optical elements. To fold down the telescope during launch and to undfold it after the satellite reached its orbit can save 70% of payload volume and 50% of payload mass. Since these advantages continue along the value added chain DST is of highest priority for the next generation of commercial EO micro satellites. Since 2002 the key technologies for DST have been developed in test benches in Labs of TU-Berlin and were tested on board a ESA parabolic flight campaign in 2005. The development team at TU-Berlin currently prepares the foundation of a start-up company for further development and commercialisation of DST.

40 CFR 63.9802 - How do I develop an emissions profile?

Code of Federal Regulations, 2013 CFR

2013-07-01

... subject to the THC concentration limit specified in item 6(a), 7(a), 8, or 9 of Table 1 to this subpart or the THC percentage reduction limit specified in item 6(b) or 7(b) of Table 1 to this subpart, you must measure and record the THC mass emissions rate at the inlet to the control device using the test methods...

40 CFR 63.9802 - How do I develop an emissions profile?

Code of Federal Regulations, 2010 CFR

2010-07-01

... subject to the THC concentration limit specified in item 6(a), 7(a), 8, or 9 of Table 1 to this subpart or the THC percentage reduction limit specified in item 6(b) or 7(b) of Table 1 to this subpart, you must measure and record the THC mass emissions rate at the inlet to the control device using the test methods...

40 CFR 63.9802 - How do I develop an emissions profile?

Code of Federal Regulations, 2014 CFR

2014-07-01

... subject to the THC concentration limit specified in item 6(a), 7(a), 8, or 9 of Table 1 to this subpart or the THC percentage reduction limit specified in item 6(b) or 7(b) of Table 1 to this subpart, you must measure and record the THC mass emissions rate at the inlet to the control device using the test methods...

40 CFR 63.9802 - How do I develop an emissions profile?

Code of Federal Regulations, 2011 CFR

2011-07-01

... subject to the THC concentration limit specified in item 6(a), 7(a), 8, or 9 of Table 1 to this subpart or the THC percentage reduction limit specified in item 6(b) or 7(b) of Table 1 to this subpart, you must measure and record the THC mass emissions rate at the inlet to the control device using the test methods...

40 CFR 63.9802 - How do I develop an emissions profile?

Code of Federal Regulations, 2012 CFR

2012-07-01

... subject to the THC concentration limit specified in item 6(a), 7(a), 8, or 9 of Table 1 to this subpart or the THC percentage reduction limit specified in item 6(b) or 7(b) of Table 1 to this subpart, you must measure and record the THC mass emissions rate at the inlet to the control device using the test methods...

Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

PubMed Central

Bastos, Mayara L.; Hussain, Hamidah; Weyer, Karin; Garcia-Garcia, Lourdes; Leimane, Vaira; Leung, Chi Chiu; Narita, Masahiro; Penã, Jose M.; Ponce-de-Leon, Alfredo; Seung, Kwonjune J.; Shean, Karen; Sifuentes-Osornio, José; Van der Walt, Martie; Van der Werf, Tjip S.; Yew, Wing Wai; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E.D.; Chiang, C.Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W.C.M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K.; Flood, J.; Gandhi, N.; Garcia-Garcia, L.; Granich, R.M.; Hollm-Delgado, M.G.; Holtz, T.H.; Hopewell, P.; Iseman, M.; Jarlsberg, L.G.; Keshavjee, S.; Kim, H.R.; Koh, W.J.; Lancaster, J.; Lange, C.; Leimane, V.; Leung, C.C.; Li, J.; Menzies, D.; Migliori, G.B.; Mitnick, C.M.; Narita, M.; Nathanson, E.; Odendaal, R.; O'Riordan, P.; Pai, M.; Palmero, D.; Park, S.K.; Pasvol, G.; Pena, J.; Pérez-Guzmán, C.; Ponce-de-Leon, A.; Quelapio, M.I.D.; Quy, H.T.; Riekstina, V.; Robert, J.; Royce, S.; Salim, M.; Schaaf, H.S.; Seung, K.J.; Shah, L.; Shean, K.; Shim, T.S.; Shin, S.S.; Shiraishi, Y.; Sifuentes-Osornio, J.; Sotgiu, G.; Strand, M.J.; Sung, S.W.; Tabarsi, P.; Tupasi, T.E.; Vargas, M.H.; van Altena, R.; van der Walt, M.; van der Werf, T.S.; Viiklepp, P.; Westenhouse, J.; Yew, W.W.; Yim, J.J.

2014-01-01

Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis. PMID:25097082

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 molar ratio of main active to inactive cannabinoids, greater than 10 was found to correlate with a strong feeling of intoxication. It also matched with a significant decrease in the willingness to drive, and it matched also with a significant impairment in tracking performances. The mathematic model II proposed by Huestis et al. (1992) provided at best a rough estimate of the time of oral administration with 27% of actual values being out of range of the 95% confidence interval. The sum of THC and 11-OH-THC blood concentrations provided a better estimate of impairment than THC alone. This controlled clinical study points out the negative influence on fitness to drive after medium or high dose oral THC or dronabinol.

The correlation between perceived social support, cortisol and brain derived neurotrophic factor levels in healthy women.

PubMed

Ma, Doy Yung; Chang, Wei Hung; Chi, Mei Hung; Tsai, Hsin Chun; Yang, Yen Kuang; Chen, Po See

2016-05-30

In this study, the role of brain derived neurotrophic factor (BDNF) in stress resilience was investigated. With a focus on healthy subjects, we explored whether plasma BDNF levels are correlated with the dexamethasone suppression test (DST) and subjectively perceived social support status. Moreover, we examined the possible interacting effect of DST status and perceived social support on BDNF levels. Seventy-two healthy volunteers, 44 females and 28 males, were recruited from the community and completed the perceived routine support subscale of Measurement of Support Function (PRS_MSF) questionnaire. Plasma BDNF levels and DST suppression rate with the low dose DST were measured. There was a significant positive correlation between BDNF and DST suppression rate in the female subjects. This was also true for the plasma BDNF levels and PRS_MSF in the female subjects. The positive correlation between BDNF and PRS_MSF was significant only in female subjects with low DST suppression rates. Plasma BDNF levels were associated with stress resilience in a sex-specific manner. Subjects' belief in social support might buffer the biological stress reactions. Differences in social perception and the biological stress response between men and women merits further investigation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Oral Fluid and Plasma Cannabinoid Ratios after Around-the-Clock Controlled Oral Δ9-Tetrahydrocannabinol Administration

PubMed Central

Milman, Garry; Schwope, David M.; Schwilke, Eugene W.; Darwin, William D.; Kelly, Deanna L.; Goodwin, Robert S.; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

BACKGROUND Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies. METHODS Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ9-tetrahydrocannabinol (THC, dronabinol) doses (40–120 mg/day) for 8 days. Plasma and OF samples were simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-μg/L, 0.5-μg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the LOQs were 0.25 μg/L for THC and THCCOOH, and 0.5 μg/L for 11-hydroxy-THC. RESULTS Despite multiple oral THC administrations each day and increasing plasma THC concentrations, OF THC concentrations generally decreased over time, reflecting primarily previously self-administered smoked cannabis. The logarithms of the THC concentrations in oral fluid and plasma were not significantly correlated (r = −0.10; P = 0.065). The OF and plasma THCCOOH concentrations, albeit with 1000-fold higher concentrations in plasma, increased throughout dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly correlated (r = 0.63; P < 0.001), although there was high interindividual variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated recent cannabis smoking. CONCLUSIONS OF monitoring does not reliably detect oral dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma and OF were different after repeated oral THC doses, and high inter-individual variation was observed. For these reasons, OF cannabinoid concentrations cannot predict concurrent plasma concentrations. PMID:21875944

[Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

PubMed

Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

2014-03-01

To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD < 15%). The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies. Pharmacokinetic parameters of THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

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

A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.

PubMed

Long, Leonora E; Chesworth, Rose; Huang, Xu-Feng; McGregor, Iain S; Arnold, Jonathon C; Karl, Tim

2010-08-01

Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats.

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats.

PubMed

Silveira, Mason M; Adams, Wendy K; Morena, Maria; Hill, Matthew N; Winstanley, Catharine A

2017-03-01

Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ 9 -Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. Male Long-Evans rats ( n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats. Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction.

Evaluation of Prevalent Phytocannabinoids in the Acetic Acid Model of Visceral Nociception

PubMed Central

Booker, Lamont; Naidu, Pattipati S.; Razdan, Raj K.; Mahadevan, Anu; Lichtman, Aron H.

2009-01-01

Considerable preclinical research has demonstrated the efficacy of Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent of Cannabis sativa, in a wide variety of animal models of pain, but few studies have examined other phytocannabinoids. Indeed, other plant-derived cannabinoids, including cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC) elicit antinociceptive effects in some assays. In contrast, tetrahydrocannabivarin (THCV), another component of cannabis, antagonizes the pharmacological effects of Δ9-THC. These results suggest that various constituents of this plant may interact in a complex manner to modulate pain. The primary purpose of the present study was to assess the antinociceptive effects of these other prevalent phytocannabinoids in the acetic acid stretching test, a rodent visceral pain model. Of the cannabinoid compounds tested, Δ9-THC and CBN bound to the CB1 receptor and produced antinociceptive effects. The CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the antinociceptive effects of both compounds. Although THCV bound to the CB1 receptor with similar affinity as Δ9-THC, it had no effects when administered alone, but antagonized the antinociceptive effects of Δ9-THC when both drugs were given in combination. Importantly, the antinociceptive effects of Δ9-THC and CBN occurred at lower doses than those necessary to produce locomotor suppression, suggesting motor dysfunction did not account for the decreases in acetic acid-induced abdominal stretching. These data raise the intriguing possibility that other constituents of cannabis can be used to modify the pharmacological effects of Δ9-THC by either eliciting antinociceptive effects (i.e., CBN) or antagonizing (i.e., THCV) the actions of Δ9-THC. PMID:19679411

Analysis of cannabis in oral fluid specimens by GC-MS with automatic SPE.

PubMed

Choi, Hyeyoung; Baeck, Seungkyung; Kim, Eunmi; Lee, Sooyeun; Jang, Moonhee; Lee, Juseon; Choi, Hwakyung; Chung, Heesun

2009-12-01

Methamphetamine (MA) is the most commonly abused drug in Korea, followed by cannabis. Traditionally, MA analysis is carried out on both urine and hair samples and cannabis analysis in urine samples only. Despite the fact that oral fluid has become increasingly popular as an alternative specimen in the field of driving under the influence of drugs (DUID) and work place drug testing, its application has not been expanded to drug analysis in Korea. Oral fluid is easy to collect and handle and can provide an indication of recent drug abuse. In this study, we present an analytical method using GC-MS to determine tetrahydrocannabinol (THC) and its main metabolite 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in oral fluid. The validated method was applied to oral fluid samples collected from drug abuse suspects and the results were compared with those in urine. The stability of THC and THC-COOH in oral fluid stored in different containers was also investigated. Oral fluid specimens from 12 drug abuse suspects, submitted by the police, were collected by direct expectoration. The samples were screened with microplate ELISA. For confirmation they were extracted using automated SPE with mixed-mode cation exchange cartridge, derivatized and analyzed by GC-MS using selective ion monitoring (SIM). The concentrations ofTHC and THC-COOH in oral fluid showed a large variation and the results from oral fluid and urine samples from cannabis abusers did not show any correlation. Thus, detailed information about time interval between drug use and sample collection is needed to interpret the oral fluid results properly. In addition, further investigation about the detection time window ofTHC and THC-COOH in oral fluid is required to substitute oral fluid for urine in drug testing.

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.

Comparative effects of pulmonary and parenteral Δ⁹-tetrahydrocannabinol exposure on extinction of opiate-induced conditioned aversion in rats.

PubMed

Manwell, Laurie A; Mallet, Paul E

2015-05-01

Evidence suggesting that the endogenous cannabinoid (eCB) system can be manipulated to facilitate or impair extinction of learned behaviours has important consequences for opiate withdrawal and abstinence. We demonstrated that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB levels, facilitates extinction of a naloxone-precipitated morphine withdrawal-induced conditioned place aversion (CPA). The potential of the exogenous CB1 ligand, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), to facilitate extinction of this CPA was tested. Effects of both pulmonary and parenteral Δ(9)-THC exposure were evaluated using comparable doses previously determined. Rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered Δ(9)-THC-pulmonary (1, 5, 10 mg vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)-prior to each of 20 to 28 extinction/testing trials. Vapourized Δ(9)-THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and 10 mg facilitated extinction compared to vehicle and 1 mg Δ(9)-THC. Injected Δ(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses. These data suggest that both dose and route of Δ(9)-THC administration have important consequences for its pharmacokinetic and behavioural effects; specifically, pulmonary exposure at higher doses facilitates, whereas pulmonary and parenteral exposure at lower doses impairs, rates of extinction learning for CPA. Pulmonary-administered Δ(9)-THC may prove beneficial for potentiation of extinction learning for aversive memories, such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and other causes of conditioned aversions, such as illness and stress.

THE PREVALENCE OF CANNABIS-INVOLVED DRIVING IN CALIFORNIA

PubMed Central

Johnson, Mark B.; Kelley-Baker, Tara; Voas, Robert B.; Lacey, John H.

2013-01-01

Background Various national surveys suggest that cannabis use is rising nationally, and many States have passed legislation that has potential to increase usage even further. This presents a problem for public roadways, as research suggests that cannabis impairs driving ability. Methods Anonymous oral fluid samples and breath tests were obtained from more than 900 weekend nighttime drivers randomly sampled from six jurisdictions in California. Oral fluid samples were assayed for the presence of Schedule I drugs. Drivers also completed information on self-reported drug use and possession of a medical cannabis permit. Data from the 2007 National Roadside Survey (collected using comparable methods) were used as a comparison. Results Using the 2010 data, a total of 14.4% of weekend nighttime drivers tested positive for illegal drugs, with 8.5% testing positive for delta-9-tetrahydrocannabinol (THC). THC-positive rates varied considerably among jurisdictions, from a low of 4.3% in Fresno to a high of 18.3% in Eureka. A comparison with the 2007 NRS data found an increase in THC-positive drivers in 2010, but no increase in illegal drugs other than cannabis. Drivers who reported having a medical cannabis permit were significantly more likely to test positive for THC. Conclusions Cannabis-involved driving has increased in California since 2007. Nearly 1-in-10 weekend, nighttime drivers tested positive for THC, and in some jurisdictions, the rate was nearly 1-in-5. The possible contribution of cannabis legislation, such as decriminalization and medical cannabis usage, is discussed. PMID:22101027

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

PubMed

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

2015-04-01

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

Daylight saving time can decrease the frequency of wildlife–vehicle collisions

PubMed Central

Ellis, William A.; FitzGibbon, Sean I.; Barth, Benjamin J.; Niehaus, Amanda C.; David, Gwendolyn K.; Taylor, Brendan D.; Matsushige, Helena; Melzer, Alistair; Bercovitch, Fred B.; Carrick, Frank; Jones, Darryl N.; Dexter, Cathryn; Gillett, Amber; Predavec, Martin; Lunney, Dan

2016-01-01

Daylight saving time (DST) could reduce collisions with wildlife by changing the timing of commuter traffic relative to the behaviour of nocturnal animals. To test this idea, we tracked wild koalas (Phascolarctos cinereus) in southeast Queensland, where koalas have declined by 80% in the last 20 years, and compared their movements with traffic patterns along roads where they are often killed. Using a simple model, we found that DST could decrease collisions with koalas by 8% on weekdays and 11% at weekends, simply by shifting the timing of traffic relative to darkness. Wildlife conservation and road safety should become part of the debate on DST. PMID:27881767

Detection of in utero cannabis exposure by umbilical cord analysis.

PubMed

Kim, Jiyoung; de Castro, Ana; Lendoiro, Elena; Cruz-Landeira, Angelines; López-Rivadulla, Manuel; Concheiro, Marta

2018-04-01

According to the 2014 National Survey on Drug Use and Health, 5.3% of pregnant women smoked marijuana in the past month. This prevalence is expected to increase as a growing number of states and countries are now considering legalization. Although the umbilical cord is becoming a useful objective tool to detect in utero drug exposure, currently data about analytical methods and its utility to detect cannabis exposure are scarce. The objective of this work was to develop a method for the determination of Δ 9 -tetrahydrocannabinol (THC), 11-hydroxyTHC (THC-OH), 11-nor-9-carboxy-THC (THCCOOH), 8-β-11-dihydroxyTHC (THC-diOH), THC and THCCOOH glucuronides, and cannabidiol (CBD) in the umbilical cord by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dual ionization source. Umbilical cord samples (0.5 g) were homogenized in methanol and extracted by solid-phase extraction. Reversed-phase chromatographic separation was performed in 14 minutes, and 2 transitions per analyte were monitored in multiple reaction monitoring mode. Method validation included linearity (1-10 to 20-200 ng/g), precision (4.1%-23.4%), accuracy (87.5%-111.4%), matrix effect (-54.8% to -5.8%), extraction efficiency (25%-45.6%), limits of detection and quantification (1-10 ng/g), and endogenous (n = 5) or exogenous interferences (not detected). The method was applied to 13 authentic samples from cannabis-exposed newborns, which meconium samples had tested positive for cannabis. Twelve cord specimens tested positive for THCCOOH-glucuronide (1.6-19.1 ng/g). We developed and validated a specific and sensitive method for the simultaneous determination of THC, its metabolites, including THC and THCCOOH glucuronides, and CBD in umbilical cord samples by LC-MS/MS. The analysis of authentic samples showed the usefulness of umbilical cord to detect cannabis in utero exposure. Copyright © 2017 John Wiley & Sons, Ltd.

Single and combined effects of Δ9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.

PubMed

King, Kirsten M; Myers, Alyssa M; Soroka-Monzo, Ariele J; Tuma, Ronald F; Tallarida, Ronald J; Walker, Ellen A; Ward, Sara Jane

2017-09-01

The non-psychoactive phytocannabinoid cannabidiol (CBD) can affect the pharmacological effects of Δ 9 -tetrahydrocannabinol (THC). We tested the possible synergy between CBD and THC in decreasing mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain. We also tested the effects of CBD on oxaliplatin- and vincristine-induced mechanical sensitivity. Paclitaxel-treated mice (8.0 mg·kg -1 i.p., days 1, 3, 5 and 7) were pretreated with CBD (0.625-20.0 mg·kg -1 i.p.), THC (0.625-20.0 mg·kg -1 i.p.) or CBD + THC (0.04 + 0.04-20.0 + 20.0 mg·kg -1 i.p.), and mechanical sensitivity was assessed on days 9, 14 and 21. Oxaliplatin-treated (6.0 mg·kg -1 i.p., day 1) or vincristine-treated mice (0.1 mg·kg -1 i.p. days 1-7) were pretreated with CBD (1.25-10.0 mg·kg -1 i.p.), THC (10.0 mg·kg -1 i.p.) or THC + CBD (0.16 mg·kg -1 THC + 0.16 mg·kg -1 CBD i.p.). Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity. CBD may be potent and effective at preventing the development of chemotherapy-induced peripheral neuropathy, and its clinical use may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of cannabis-based pharmacotherapies. © 2017 The British Pharmacological Society.

Increase in cannabis use may indirectly affect the health status of a freshwater species.

PubMed

Parolini, Marco; Castiglioni, Sara; Magni, Stefano; Della Torre, Camilla; Binelli, Andrea

2017-02-01

Cannabis is the most used illicit drug worldwide and in some countries a new regulatory policy makes it legal under some restrictions. This situation could lead to a substantial increase in environmental levels of the cannabis active principle (Δ-9-tetrahydrocannabinol [Δ-9-THC]) and its main metabolite, 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THC-COOH). Although previous studies have highlighted the toxicity of Δ-9-THC, the adverse effects of THC-COOH on aquatic organisms is completely unknown, even though such effects could be more significant because the environmental concentrations of THC-COOH are higher than those of the parent compound. The present study aimed to assess oxidative and genetic damage to the zebra mussel (Dreissena polymorpha) because of 14-d exposures to 3 THC-COOH concentrations, mimicking a current environmental situation (100 ng/L), as well as exposure to 2 possible worst-case scenarios (500 ng/L and 1000 ng/L), because of the potential increase in THC-COOH in surface waters. Variations in the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured, as well as levels of lipid peroxidation and protein carbonyl content. Genetic injuries were investigated by single-cell gel electrophoresis assay, DNA diffusion assay, and the micronucleus test. A significant imbalance in antioxidant defense enzymes was noted in response to the 3 tested concentrations, whereas oxidative damage was noted only at the higher one. Moreover, an increase in DNA fragmentation in zebra mussel hemocytes, but no fixed genetic damage, was found. Although the results showed that THC-COOH toxicity was lower than that of Δ-9-THC, the increase in cannabis use might increase its levels in freshwaters, enhancing its hazard to bivalves and likely to the whole aquatic community. Environ Toxicol Chem 2017;36:472-479. © 2016 SETAC. © 2016 SETAC.

Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users.

PubMed

Taylor, Michelle; Lees, Rosie; Henderson, Graeme; Lingford-Hughes, Anne; Macleod, John; Sullivan, John; Hickman, Matthew

2017-03-01

Biological tests of drug use can be used to inform clinical and legal decisions and hold potential to provide evidence for epidemiological studies where self-reported behaviour may be unavailable or unreliable. We test whether hair can be considered as a reliable marker of cannabis exposure. Hair samples were collected from 136 subjects who were self-reported heavy, light or non-users of cannabis and tested using GC-MS/MS. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for five cannabinoids (tetrahydrocannabinol [THC], THC-OH, THC-COOH, cannabinol and cannabidiol). Samples also were segmented in 1 cm sections representing 1 month exposure and the correlation between amount of cannabinoid detected and self-reported cannabis consumption tested. All five cannabinoids were detected. Seventy-seven percent of heavy users, 39% of light users and 0% of non-users tested positive for THC. The sensitivity of detection of THC was 0.77 (0.56-0.91) comparing heavy cannabis smokers with light and non-users, whereas the sensitivity of other cannabinoids generally was considerably lower. The positive and negative predictive value of detection of THC were 0.57 (0.39-0.74) and 0.91 (0.82-0.97), respectively. A correlation of 0.52 (P < 0.001) was observed between self-reported monthly cannabis use and THC. Hair analysis can be used as a qualitative indicator of heavy (daily or near daily) cannabis consumption within the past 3 months. However, this approach is unable to reliably detect light cannabis consumption or determine the quantity of cannabis used by the individual. [Taylor M, Lees R, Henderson G, Lingford-Hughes A, Macleod J, Sullivan J, Hickman M. Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users. Drug Alcohol Rev 2017;36:220-226]. © 2016 The Authors Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats.

PubMed

Rock, Erin M; Limebeer, Cheryl L; Petrie, Gavin N; Williams, Lauren A; Mechoulam, Raphael; Parker, Linda A

2017-07-01

Cannabis is commonly used by humans to relieve stress. Here, we evaluate the potential of intraperitoneally (i.p.) administered Δ 9 -tetrahydrocannabiol (THC) and cannabidiolic acid (CBDA, the precursor of cannabidiol [CBD]) to produce dose-dependent effects on anxiety-like responding in the light-dark (LD) emergence test of anxiety-like responding in rats, when administered acutely or chronically (21 days). As well, we evaluate the potential of THC, CBDA, and CBD to reduce anxiogenic responding produced by foot shock (FS) stress 24 h prior to the LD test. In the absence of the explicit FS stressor, THC (1 and 10 mg/kg) produced anxiogenic-like responding when administered acutely or chronically, but CBDA produced neither anxiogenic- nor anxiolytic-like responding. Administration of FS stress 24 h prior to the LD test enhanced anxiogenic-like responding (reduced time spent and increased latency to enter the light compartment) in rats pretreated with either vehicle (VEH) or THC (1 mg/kg); however, administration of CBDA (0.1-100 μg/kg) or CBD (5 mg/kg) prevented the FS-induced anxiogenic-like responding (an anxiolytic-like effect). The 5-hydroxytryptamine 1A (5-HT 1A ) receptor antagonist, WAY100635, reversed CBDA's anxiolytic effect (1 μg/kg). Combining an anxiolytic dose of CBDA (1 μg/kg) or CBD (5 mg/kg) with an anxiogenic dose of THC (1 mg/kg) did not modify THC's anxiogenic effect. These results suggest the anxiolytic effects of CBDA and CBD may require the presence of a specific stressor.

Adulteration of urine by "Urine Luck".

PubMed

Wu, A H; Bristol, B; Sexton, K; Cassella-McLane, G; Holtman, V; Hill, D W

1999-07-01

In vitro adulterants are used to invalidate assays for urine drugs of abuse. The present study examined the effect of pyridinium chlorochromate (PCC) found in the product "Urine Luck". PCC was prepared and added to positive urine controls at concentrations of 0, 10, 50, and 100 g/L. The controls were assayed for methamphetamine, benzoylecgonine (BE), codeine and morphine, tetrahydrocannabinol (THC), and phencyclidine (PCP) with the Emit II (Syva) and Abuscreen Online (Roche) immunoassays, and by gas chromatography/mass spectrometry (GC/MS). Two tests were also developed to detect PCC in urine: a spot test to detect chromate ions using 10 g/L 1,5-diphenylcarbazide as the indicator, and a GC/MS assay for pyridine. We tested 150 samples submitted for routine urinalysis, compliance, and workplace drug testing for PCC, using these assays. Response rates decreased at 100 g/L PCC for all Emit II drug assays and for the Abuscreen morphine and THC assays. In contrast, the Abuscreen amphetamine assay produced apparently higher results, and no effect was seen on the results for BE or PCP. The PCC did not affect the GC/MS recovery of methamphetamine, BE, PCP, or their deuterated internal standards, but decreased GC/MS recovery of the opiates at both intermediate (50 g/L) and high (100 g/L) PCC concentrations and apparent concentrations of THC and THC-d3 at all PCC concentrations. Two of 50 samples submitted for workplace drug testing under chain-of-custody conditions were positive for PCC, whereas none of the remaining 100 specimens submitted for routine urinalysis or compliance drug testing were positive. PCC is an effective adulterant for urine drug testing of THC and opiates. Identification of PCC use can be accomplished with use of a spot test for the oxidant.

Provider reported barriers and solutions to improve testing among tuberculosis patients ‘eligible for drug susceptibility test’: A qualitative study from programmatic setting in India

PubMed Central

Parmar, Malik; Verma, Manoj; Desikan, Prabha; Khan, Sheeba Naz; Kumar, Ajay M. V.

2018-01-01

Background In a study conducted in Bhopal district (a setting with facility for molecular drug susceptibility testing (DST)) located in central India in 2014–15, we found high levels of pre-diagnosis attrition among patients with presumptive multi drug-resistant tuberculosis (MDR-TB)–meaning TB patients who were eligible for DST, were not being tested. Objectives In this study, we explored the health care provider perspectives into barriers and suggested solutions for improving DST. Methods This was a descriptive qualitative study. One to one interviews (n = 10) and focus group discussions (n = 2) with experienced key informants involved in programmatic management of DR-TB were conducted in April 2017. Manual descriptive thematic analysis was performed. Results The key barriers reported were a) lack of or delay in identification of patients eligible for DST because of using treatment register as the source for identifying patients b) lack of assured specimen transport after patient identification and c) lack of tracking. Extra pulmonary TB patients were not getting identified as eligible for DST. Solutions suggested by the health care providers were i) generation of unique identifier at identification in designated microscopy center (DMC), immediate intimation of unique identifier to district and regular monitoring by senior TB laboratory and senior treatment supervisors of patients eligible for DST that were missed; ii) documentation of unique identifier at each step of cascade; iii) use of human carriers/couriers to transport specimen from DMCs especially in rural areas; and iv) routine entry of all presumptive extra-pulmonary TB specimen, as far as possible, in DMC laboratory register. Conclusion Lack of assured specimen transport and lack of accountability for tracking patient after identification and referral were the key barriers. The identification of patients eligible for DST among microbiologically confirmed TB at the time of diagnosis and among clinically confirmed TB at the time of treatment initiation is the key. Use of unique identifier at identification and its use to ensure cohort wise tracking has to be complemented with specimen transport support and prompt feedback to the DMC. The study has implications to improve detection of MDR-TB among diagnosed/notified TB patients. PMID:29677210

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats

PubMed Central

Silveira, Mason M.; Adams, Wendy K.; Morena, Maria; Hill, Matthew N.; Winstanley, Catharine A.

2017-01-01

Background Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. Methods Male Long–Evans rats (n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. Results We found that THC decreased choice of hard trials without impairing the animals’ ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex — an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in “slacker” rats. Limitations Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. Conclusion These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction. PMID:28245177

Implementation of the national tuberculosis guidelines on culture and drug sensitivity testing in Guatemala, 2013.

PubMed

Samayoa-Peláez, Maritza; Ayala, Nancy; Yadon, Zaida E; Heldal, Einar

2016-01-01

Objective To assess whether the National Tuberculosis Program (NTP) guidelines for culture and drug sensitivity testing (DST) in Guatemala were successfully implemented, particularly in cases of smear-negative pulmonary tuberculosis (TB) or previously treated TB, by documenting notification rates by department (geographic area), disease type and category, and culture and DST results. Methods This was a cross-sectional, operational research study that merged and linked all patients registered by the NTP and the National Reference Laboratory in 2013, eliminating duplicates. The proportions with culture (for new smear negative pulmonary cases) and culture combined with DST (for previously treated patients) were estimated and analyzed by department. Data were analyzed using EpiData Analysis version 2.2. Results There were 3 074 patients registered with TB (all forms), for a case notification rate of 20/100 000 population. Of these, 2 842 had new TB, of which 2 167 (76%) were smear-positive pulmonary TB (PTB), 385 (14%) were smear-negative PTB, and 290 (10%) were extrapulmonary TB. There were 232 (8%) previously treated cases. Case notification rates (all forms) varied by department from 2-68 per 100 000 population, with the highest rates seen in the southwest and northeast part of Guatemala. Of new TB patients, 136 had a culture performed and 55 had DST of which the results were 33 fully sensitive, 9 monoresistant, 3 polyresistant, and 10 multidrug resistant TB (MDR-TB). Only 21 (5%) of new smear-negative PTB patients had cultures. Of 232 previously treated patients, 54 (23%) had a culture and 47 (20%) had DST, of which 29 were fully sensitive, 7 monoresistant, 2 polyresistant, and 9 MDR-TB. Of 22 departments (including the capital), culture and DST was performed in new smear-negative PTB in 7 departments (32%) and in previously treated TB in 13 departments (59%). Conclusions Despite national guidelines, only 5% of smear-negative PTB cases had a culture and only 20% of previously treated TB had a culture and DST. Several departments did not perform culture or DST. These short comings must be improved if Guatemala is to curtail the spread of drug resistant forms of TB, while striving to eliminate all TB.

φ(2)GFP10, a high-intensity fluorophage, enables detection and rapid drug susceptibility testing of Mycobacterium tuberculosis directly from sputum samples.

PubMed

Jain, Paras; Hartman, Travis E; Eisenberg, Nell; O'Donnell, Max R; Kriakov, Jordan; Govender, Karnishree; Makume, Mantha; Thaler, David S; Hatfull, Graham F; Sturm, A Willem; Larsen, Michelle H; Moodley, Preshnie; Jacobs, William R

2012-04-01

The difficulty of diagnosing active tuberculosis (TB) and lack of rapid drug susceptibility testing (DST) at the point of care remain critical obstacles to TB control. This report describes a high-intensity mycobacterium-specific-fluorophage (φ(2)GFP10) that for the first time allows direct visualization of Mycobacterium tuberculosis in clinical sputum samples. Engineered features distinguishing φ(2)GFP10 from previous reporter phages include an improved vector backbone with increased cloning capacity and superior expression of fluorescent reporter genes through use of an efficient phage promoter. φ(2)GFP10 produces a 100-fold increase in fluorescence per cell compared to existing reporter phages. DST for isoniazid and oxofloxacin, carried out in cultured samples, was complete within 36 h. Use of φ(2)GFP10 detected M. tuberculosis in clinical sputum samples collected from TB patients. DST for rifampin and kanamycin from sputum samples yielded results after 12 h of incubation with φ(2)GFP10. Fluorophage φ(2)GFP10 has potential for clinical development as a rapid, sensitive, and inexpensive point-of-care diagnostic tool for M. tuberculosis infection and for rapid DST.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.

PubMed

Domínguez, J; Boettger, E C; Cirillo, D; Cobelens, F; Eisenach, K D; Gagneux, S; Hillemann, D; Horsburgh, R; Molina-Moya, B; Niemann, S; Tortoli, E; Whitelaw, A; Lange, C

2016-01-01

The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

Dexamethasone suppression test

MedlinePlus

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

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.

Amphetamines and cannabinoids testing in hair: Evaluation of results from a two-year period.

PubMed

Burgueño, María José; Alonso, Amaya; Sánchez, Sergio

2016-08-01

This paper presents an overview of a set of amphetamines and cannabinoids tests performed on head hair samples from the Medico-Legal sector at the Madrid Department of the Spanish National Institute of Toxicology and Forensic Sciences during the years 2013 and 2014. The hair samples were tested for five stimulant phenylalkylamine derivatives -amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)- and/or two cannabinoids-Δ(9)-tetrahydrocannabinol (THC) and cannabinol (CBN)- by gas chromatography equipped with mass spectrometry detection in selected-ion monitoring mode, applying a method accredited to ISO/IEC 17025 standards. The test results were interpreted according to the confirmation cut-offs proposed by the Society of Hair Testing (SoHT) to identify chronic drug use. The ratios of positive results were studied in relation to gender, age, hair colour, dyeing and length of the tested samples to assess the independence from these variables or the association with them. Low, medium and high ranges of concentration were also estimated for each drug. 21.94% of the 2954 hair samples tested for phenylalkylamine derivatives were positive for one or more substances. 16.38% of the samples were positive for AP, 12.09% for MDMA and only 0.44% for MA. 6.60% of the tested samples were positive for AP/MDMA combination. A total of 3178 samples were tested for cannabinoids, resulting in 53.40% positive for THC and CBN. Simultaneous tests for phenylalkylamine derivatives and cannabinoids were performed in 2931 of the samples; 14.94% of them were positive for THC, CBN, and one or more amphetamines. According to the results from the statistical analysis, the use of THC and MDMA vary with age and gender among the Medico-Legal sector in an extended area of Spain, while the use of AP appears to be independent of these variables. On the other hand, the results of THC in hair could be influenced by the length of the tested segment; therefore, a consensus regarding the hair length between 3.0 and 5.5cm for THC testing should be reached. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans

PubMed Central

Braley, Gabriel; Blaise, Rebecca; Vendetti, Michael; Oliver, Stephen; Pittman, Brian; Ranganathan, Mohini; Bhakta, Savita; Zimolo, Zoran; Cooper, Thomas; Perry, Edward

2010-01-01

Introduction Cannabinoids produce a spectrum of effects in humans including euphoria, cognitive impairments, psychotomimetic effects, and perceptual alterations. The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol (Δ-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans. Materials and methods In a 2-test-day double-blind study, 28 subjects including healthy subjects (n=17) and frequent users of cannabis (n=11) were administered active (0.057 mg/kg) or placebo oral haloperidol in random order followed 90 and 215 min later by fixed order intravenous administration of placebo (vehicle) and active (0.0286 mg/kg) Δ-9-THC, respectively. Results Consistent with previous reports, intravenous Δ-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including “high.” Δ-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC. Haloperidol and Δ-9-THC worsened distractibility and vigilance. Neither drug impaired performance on a motor screening task, the Stockings of Cambridge task, or the delayed match to sample task. Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments. Conclusions The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Δ-9-THC and to better understand the crosstalk between DAergic and CBergic systems. PMID:18228005

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.

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.

Daylight saving time can decrease the frequency of wildlife-vehicle collisions.

PubMed

Ellis, William A; FitzGibbon, Sean I; Barth, Benjamin J; Niehaus, Amanda C; David, Gwendolyn K; Taylor, Brendan D; Matsushige, Helena; Melzer, Alistair; Bercovitch, Fred B; Carrick, Frank; Jones, Darryl N; Dexter, Cathryn; Gillett, Amber; Predavec, Martin; Lunney, Dan; Wilson, Robbie S

2016-11-01

Daylight saving time (DST) could reduce collisions with wildlife by changing the timing of commuter traffic relative to the behaviour of nocturnal animals. To test this idea, we tracked wild koalas (Phascolarctos cinereus) in southeast Queensland, where koalas have declined by 80% in the last 20 years, and compared their movements with traffic patterns along roads where they are often killed. Using a simple model, we found that DST could decrease collisions with koalas by 8% on weekdays and 11% at weekends, simply by shifting the timing of traffic relative to darkness. Wildlife conservation and road safety should become part of the debate on DST. © 2016 The Author(s).

A Field Evaluation of the Hardy TB MODS Kit™ for the Rapid Phenotypic Diagnosis of Tuberculosis and Multi-Drug Resistant Tuberculosis

PubMed Central

Martin, Laura; Coronel, Jorge; Faulx, Dunia; Valdez, Melissa; Metzler, Mutsumi; Crudder, Chris; Castillo, Edith; Caviedes, Luz; Grandjean, Louis; Rodriguez, Mitzi; Friedland, Jon S.; Gilman, Robert H.; Moore, David A. J.

2014-01-01

Background Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. Methods & Findings 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3–99.8%), 98.3% (97.5–98.8%), 95.8% (94.0–97.1%), and 99.7% (99.3–99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9–13) days for conventional MODS and 8.5 (7–11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). Conclusions MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of access to TB diagnosis and first and second-line DST in settings where the need is greatest. PMID:25225802

A field evaluation of the Hardy TB MODS Kit™ for the rapid phenotypic diagnosis of tuberculosis and multi-drug resistant tuberculosis.

PubMed

Martin, Laura; Coronel, Jorge; Faulx, Dunia; Valdez, Melissa; Metzler, Mutsumi; Crudder, Chris; Castillo, Edith; Caviedes, Luz; Grandjean, Louis; Rodriguez, Mitzi; Friedland, Jon S; Gilman, Robert H; Moore, David A J

2014-01-01

Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of access to TB diagnosis and first and second-line DST in settings where the need is greatest.

Comparison of Dst Forecast Models for Intense Geomagnetic Storms

NASA Technical Reports Server (NTRS)

Ji, Eun-Young; Moon, Y.-J.; Gopalswamy, N.; Lee, D.-H.

2012-01-01

We have compared six disturbance storm time (Dst) forecast models using 63 intense geomagnetic storms (Dst <=100 nT) that occurred from 1998 to 2006. For comparison, we estimated linear correlation coefficients and RMS errors between the observed Dst data and the predicted Dst during the geomagnetic storm period as well as the difference of the value of minimum Dst (Delta Dst(sub min)) and the difference in the absolute value of Dst minimum time (Delta t(sub Dst)) between the observed and the predicted. As a result, we found that the model by Temerin and Li gives the best prediction for all parameters when all 63 events are considered. The model gives the average values: the linear correlation coefficient of 0.94, the RMS error of 14.8 nT, the Delta Dst(sub min) of 7.7 nT, and the absolute value of Delta t(sub Dst) of 1.5 hour. For further comparison, we classified the storm events into two groups according to the magnitude of Dst. We found that the model of Temerin and Lee is better than the other models for the events having 100 <= Dst < 200 nT, and three recent models (the model of Wang et al., the model of Temerin and Li, and the model of Boynton et al.) are better than the other three models for the events having Dst <= 200 nT.

Correlation between Genotypic and Phenotypic Testing for Resistance to Rifampin in Mycobacterium tuberculosis Clinical Isolates in Haiti: Investigation of Cases with Discrepant Susceptibility Results

PubMed Central

Ocheretina, Oksana; Escuyer, Vincent E.; Mabou, Marie-Marcelle; Royal-Mardi, Gertrude; Collins, Sean; Vilbrun, Stalz C.; Pape, Jean W.; Fitzgerald, Daniel W.

2014-01-01

The World Health Organization has recommended use of molecular-based tests MTBDRplus and GeneXpert MTB/RIF to diagnose multidrug-resistant tuberculosis in developing and high-burden countries. Both tests are based on detection of mutations in the Rifampin (RIF) Resistance-Determining Region of DNA-dependent RNA Polymerase gene (rpoB). Such mutations are found in 95–98% of Mycobacterium tuberculosis strains determined to be RIF-resistant by the “gold standard” culture-based drug susceptibility testing (DST). We report the phenotypic and genotypic characterization of 153 consecutive clinical Mycobacterium tuberculosis strains diagnosed as RIF-resistant by molecular tests in our laboratory in Port-au-Prince, Haiti. 133 isolates (86.9%) were resistant to both RIF and Isoniazid and 4 isolates (2.6%) were RIF mono-resistant in MGIT SIRE liquid culture-based DST. However the remaining 16 isolates (10.5%) tested RIF-sensitive by the assay. Five strains with discordant genotypic and phenotypic susceptibility results had RIF minimal inhibitory concentration (MIC) close to the cut-off value of 1 µg/ml used in phenotypic susceptibility assays and were confirmed as resistant by DST on solid media. Nine strains had sub-critical RIF MICs ranging from 0.063 to 0.5 µg/ml. Finally two strains were pan-susceptible and harbored a silent rpoB mutation. Our data indicate that not only detection of the presence but also identification of the nature of rpoB mutation is needed to accurately diagnose resistance to RIF in Mycobacterium tuberculosis. Observed clinical significance of low-level resistance to RIF supports the re-evaluation of the present critical concentration of the drug used in culture-based DST assays. PMID:24599230

Marijuana poisoning.

PubMed

Fitzgerald, Kevin T; Bronstein, Alvin C; Newquist, Kristin L

2013-02-01

The plant Cannabis sativa has been used for centuries for the effects of its psychoactive resins. The term "marijuana" typically refers to tobacco-like preparations of the leaves and flowers. The plant contains more than 400 chemicals but the cannabinoid δ-9-tetrahydrocannabinol (THC) is the major psychoactive constituent. "Hashish" is the resin extracted from the tops of flowering plants and generally has a much higher THC concentration. Marijuana is the most commonly used illicit drug in the United States. Currently, several states have passed legislation to decriminalize possession of small amounts of marijuana for both medical and personal use and several other states have similar legislation under consideration. The most common form of marijuana use in humans is inhalation of the smoke of marijuana cigarettes, followed by ingestion. In animals, although secondhand smoke inhalation is possible, the most common source of exposure is through ingestion of the owner's marijuana supply. The minimum lethal oral dose for dogs for THC is more than 3 g/kg. Although the drug has a high margin of safety, deaths have been seen after ingestion of food products containing the more concentrated medical-grade THC butter. There are two specific cannabinoid receptors in humans and dogs, CB1 (primarily in central nervous system) and CB2 (peripheral tissues). In animals, following oral ingestion, clinical effects begin within 60 minutes. All of the neuropharmacologic mechanisms by which cannabinoids produce psychoactive effects have not been identified. However, CB1 activity is believed to be responsible for the majority of cannabinoid clinical effects. Highly lipid soluble, THC is distributed in fat, liver, brain, and renal tissue. Fifteen percent of THC is excreted into the urine and the rest is eliminated in the feces through biliary excretion. Clinical signs of canine intoxication include depression, hypersalivation, mydriasis, hypermetria, vomiting, urinary incontinence, tremors, hypothermia, and bradycardia. Higher dosages may additionally cause nystagmus, agitation, tachypnea, tachycardia, ataxia, hyperexcitability, and seizures. Treatment of marijuana ingestion in animals is largely supportive. Vital signs including temperature and heart rate and rhythm must be continually monitored. Stomach content and urine can be tested for cannabinoids. Gas chromatography and mass spectrometry can be utilized for THC detection but usually may take several days and are not practical for initiation of therapy. Human urine drug-screening tests can be unreliable for confirmation of marijuana toxicosis in dogs owing to the interference of a large number of the metabolites in canine urine. False negatives may also arise if testing occurs too recently following THC ingestion. Thus, the use of human urine drug-screening tests in dogs remains controversial. No specific antidote presently exists for THC poisoning. Sedation with benzodiazepines may be necessary if dogs are severely agitated. Intravenous fluids may be employed to counter prolonged vomiting and to help control body temperature. Recently, the use of intralipid therapy to bind the highly lipophilic THC has been utilized to help reduce clinical signs. The majority of dogs experiencing intoxication after marijuana ingestion recover completely without sequellae. Differential diagnoses of canine THC toxicosis include human pharmaceuticals with central nervous system stimulatory effects, drugs with central nervous system depressant effects, macrolide parasiticides, xylitol, and hallucinogenic mushrooms. Copyright © 2013 Elsevier Inc. All rights reserved.

CSF 5-HIAA and DST non-suppression--orthogonal biologic risk factors for suicide in male mood disorder inpatients.

PubMed

Jokinen, Jussi; Nordström, Anna-Lena; Nordström, Peter

2009-01-30

Two biomarkers of suicide risk; non-suppression in the dexamethasone suppression test (DST) and low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been reported to be predictors of suicide in mood disorders. The interrelation of the two systems seems to be different in suicide attempters compared with depressed inpatients who have not made a suicide attempt, indicating that the two biomarkers may be seen as independent. This investigation examined the interrelation of low CSF 5-HIAA and DST non-suppression in suicide victims with mood disorder. Fifty-eight mood disorder inpatients not receiving any treatment with antidepressants underwent lumbar puncture and the DST. Plasma cortisol levels at 8:00 a.m., 4:00 p.m. and 11:00 p.m. were analysed in relation to CSF 5-HIAA. All patients were followed up for causes of death and suicides were verified with death certificates. During follow-up (mean 21 years), 11 (19%) patients had committed suicide. In male suicide victims (n=6), the serum cortisol level at 4:00 p.m. showed a significant positive correlation with CSF 5-HIAA. Low CSF 5-HIAA predicted all early suicides (within 1 year), whereas all males who committed suicide after 1 year were DST non-suppressors. In female suicide victims (n=5), the post-DST serum cortisol did not correlate with CSF 5-HIAA. Low CSF 5-HIAA and DST non-suppression are orthogonal biologic risk factors for suicide in male mood disorder inpatients. CSF 5-HIAA is associated with short-term suicide risk; dysregulation of the hypothalamic-pituitary-adrenal axis seems to be a long-term suicide predictor.

New diagnostic criteria of adrenal subclinical Cushing's syndrome: opinion from the Japan Endocrine Society.

PubMed

Yanase, Toshihiko; Oki, Yutaka; Katabami, Takuyuki; Otsuki, Michio; Kageyama, Kazunori; Tanaka, Tomoaki; Kawate, Hisaya; Tanabe, Makito; Doi, Masaru; Akehi, Yuko; Ichijo, Takamasa

2018-04-26

New diagnostic criteria and the treatment policy for adrenal subclinical Cushing's syndrome (SCS) are proposed on behalf of the Japan Endocrine Society. The Japanese version has been published, and the essential contents are presented in this English-language version. The current diagnostic criteria for SCS have elicited two main problems: (i) the relatively low reliability of a low range of serum cortisol essential for the diagnosis by an overnight 1-mg dexamethasone suppression test (DST); (ii) different cutoff values for serum cortisol after a 1-mg DST compared with those of other countries. Thus, new criteria are needed. In the new criteria, three hierarchical cortisol cutoff values, 5.0, 3.0 and 1.8 μg/dL, after a 1-mg DST are presented. Serum cortisol ≥5 μg/dL after a 1-mg DST alone is considered sufficient to judge autonomous cortisol secretion for the diagnosis of SCS, and the current criterion based on serum cortisol ≥3 μg/dL after a 1-mg DST can continue to be used. Clinical evidence suggests that serum cortisol ≥1.8-2.9 μg/dL after a 1-mg DST is not always normal, so cases who meet the cutoff value as well as a basal adrenocorticotropic hormone (ACTH) level <10 pg/mL (or poor ACTH response to corticotropin-releasing hormone (CRH)) and nocturnal serum cortisol ≥5 μg/dL are proposed to have SCS. We suggest surgery if cases show serum cortisol ≥5 μg/dL after a 1-mg DST (or are disheartened by treatment-resistant problems) or suspicious cases of adrenal cancer according to tumor imaging.

Is 2-Hydroxypropyl-β-cyclodextrin a Suitable Carrier for Central Administration of Δ9 -Tetrahydrocannabinol? Preclinical Evidence.

PubMed

Agabio, R; Sanna, F; Lobina, C; Monduzzi, M; Nairi, V; Cugia, F; Mameli, S; Pisanu, G M; Gessa, G L; Melis, M R

2017-12-01

Preclinical Research Δ 9 -Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPβCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPβCD (30 and 135 μg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 μg of THC/HPβCD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 μg THC/HPβCD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HPβCD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411-419, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

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

PubMed

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

2008-12-01

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

Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

PubMed

Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

2015-01-01

To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

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.

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.

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.

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

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.

Post-dexamethasone Cortisol, Self-inflicted Injury, and Suicidal Ideation among Depressed Adolescent Girls

PubMed Central

Beauchaine, Theodore P.; Crowell, Sheila E.; Hsiao, Ray C.

2014-01-01

Although the dexamethasone suppression test (DST) has limited use as a marker of depression given inadequate sensitivity and specificity, it marks prospective risk for suicide among adults. However, few studies have examined associations between the DST, suicidal ideation, and self-inflicted injury (SII) among adolescents, even though SII is the single best predictor of eventual suicide. We evaluated the DST as a correlate of suicidal ideation and retrospective reports of self-inflicted injury (SII) among adolescent girls, ages 13–17, with histories of depression (n=28) or depression/self-harm (n=29). Lower post-DST cortisol was associated with suicidal ideation and SII, over-and-above parent-reports and combined parent-/self-reports of internalizing and externalizing behavior. These findings are consistent with recent acquired capacity models of stress-related psychopathology in which hypothalamic-pituitary adrenal (HPA) axis function is altered through epigenetic/allostatic mechanisms among vulnerable individuals who incur adversity early in life. PMID:25208812

Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two.

PubMed

McPartland, John M; MacDonald, Christa; Young, Michelle; Grant, Phillip S; Furkert, Daniel P; Glass, Michelle

2017-01-01

Introduction: Cannabis biosynthesizes Δ 9 -tetrahydrocannabinolic acid (THCA-A), which decarboxylates into Δ 9 -tetrahydrocannabinol (THC). There is growing interest in the therapeutic use of THCA-A, but its clinical application may be hampered by instability. THCA-A lacks cannabimimetic effects; we hypothesize that it has little binding affinity at cannabinoid receptor 1 (CB 1 ). Materials and Methods: Purity of certified reference standards were tested with high performance liquid chromatography (HPLC). Binding affinity of THCA-A and THC at human (h) CB 1 and hCB 2 was measured in competition binding assays, using transfected HEK cells and [ 3 H]CP55,940. Efficacy at hCB 1 and hCB 2 was measured in a cyclic adenosine monophosphase (cAMP) assay, using a Bioluminescence Resonance Energy Transfer (BRET) biosensor. Results: The THCA-A reagent contained 2% THC. THCA-A displayed small but measurable binding at both hCB 1 and hCB 2 , equating to approximate K i values of 3.1μM and 12.5μM, respectively. THC showed 62-fold greater affinity at hCB 1 and 125-fold greater affinity at hCB 2 . In efficacy tests, THCA-A (10μM) slightly inhibited forskolin-stimulated cAMP at hCB 1 , suggestive of weak agonist activity, and no measurable efficacy at hCB 2 . Discussion: The presence of THC in our THCA-A certified standard agrees with decarboxylation kinetics (literature reviewed herein), which indicate contamination with THC is nearly unavoidable. THCA-A binding at 10μM approximated THC binding at 200nM. We therefore suspect some of our THCA-A binding curve was artifact-from its inevitable decarboxylation into THC-and the binding affinity of THCA-A is even weaker than our estimated values. We conclude that THCA-A has little affinity or efficacy at CB 1 or CB 2 .

Determination of cannabinoids in hemp nut products in Taiwan by HPLC-MS/MS coupled with chemometric analysis: quality evaluation and a pilot human study.

PubMed

Chang, Chih-Wei; Tung, Chun-Wei; Tsai, Chin-Chuan; Wu, Yu-Tse; Hsu, Mei-Chich

2017-06-01

Hemp nuts are mature cannabis seeds obtained after shelling and that are commonly used in traditional Chinese medicine for treating functional constipation. In this work, we screened hemp nut products, classified them, and verified the legality of consuming them. A total of 18 products were purchased from Taiwan, China, and Canada. Validated high-performance liquid chromatography with tandem mass spectrometry methods were developed for analyzing the cannabinoid (i.e., Δ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol) content of the products and the concentration of urinary 11-nor-9-carboxy-THC. Chemometric techniques, namely hierarchical clustering analysis (HCA) and principal component analysis (PCA), were applied for rapidly classifying 11 concentrated powder products in Taiwan. A pilot human study comprising single and multiple administrations of a product with 1.5 µg/g of THC was conducted to examine the urinary 11-nor-9-carboxy-THC concentration. Through optimization of 3 2 full factorial design, using 60% isopropanol as the extraction solvent exhibited the highest yield of cannabinoids and was applied as the optimal condition in further analysis. The results of HCA and PCA on quality evaluation were in good agreement; however, the tested products possessed distinct CBD-to-THC ratios which ranged widely from 0.1:1 to 46.8:1. Particularly, the products with CBD-to-THC ratios higher than 1:1 were the majority in Taiwan. Our data suggested that all the tested hemp nut products met the Taiwan restriction criterion of 10 µg/g of THC. We propose a usual consumption amount of hemp nut products in Taiwan would unlikely to violate the cut-off point of 15 ng/mL of urinary 11-nor-9-carboxy-THC. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Micro-pulverized extraction pretreatment for highly sensitive analysis of 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol in hair by liquid chromatography/tandem mass spectrometry.

PubMed

Kuwayama, Kenji; Miyaguchi, Hajime; Yamamuro, Tadashi; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

2015-11-30

A primary metabolite of Δ(9) -tetrahydrocannabinol, 11-nor-9-carboxytetrahydrocannabinol (THC-COOH), serves as an effective indicator for cannabis intake. According to the recommendations of the Society of Hair Testing, at least 0.2 pg/mg of THC-COOH (cut-off level) must be present in a hair sample to constitute a positive result in a drug test. Typically, hair is digested with an alkaline solution and is subjected to gas chromatography/tandem mass spectrometry (GC/MS/MS) with negative ion chemical ionization (NICI). It is difficult to quantify THC-COOH at the cut-off level using liquid chromatography/tandem mass spectrometry (LC/MS/MS) without acquisition of second-generation product ions in triple quadrupole-ion trap mass spectrometers, because large amounts of matrix components in the low-mass range produced by digestion interfere with the THC-COOH peak. Using the typical pretreatment method (alkaline dissolution) and micro-pulverized extraction (MPE) with a stainless bullet, we compared the quantification of THC-COOH using GC/MS/MS and LC/MS/MS. MPE reduced the amount of matrix components in the low-mass range and enabled the quantification of THC-COOH at 0.2 pg/mg using a conventional triple quadrupole liquid chromatograph coupled to a mass spectrometer. On the other hand, the MPE pretreatment was unsuitable for GC/MS/MS, probably due to matrix components in the high-mass range. The proper combination of pretreatments and instrumental analyses was shown to be important for detecting trace amounts of THC-COOH in hair. In MPE, samples can be prepared rapidly, and LC/MS/MS is readily available, unlike GC/MS/MS with NICI. The combination of MPE and LC/MS/MS might therefore be used in the initial screening for THC-COOH in hair prior to confirmatory analysis using GC/MS/MS with NICI. Copyright © 2015 John Wiley & Sons, Ltd.

Optimization of recombinant β-glucuronidase hydrolysis and quantification of eight urinary cannabinoids and metabolites by liquid chromatography tandem mass spectrometry.

PubMed

Sempio, Cristina; Scheidweiler, Karl B; Barnes, Allan J; Huestis, Marilyn A

2018-03-01

Prolonged urinary cannabinoid excretion in chronic frequent cannabis users confounds identification of recent cannabis intake that may be important in treatment, workplace, clinical, and forensic testing programs. In addition, differentiation of synthetic Δ9-tetrahydrocannabinol (THC) intake from cannabis plant products might be an important interpretive issue. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) urine concentrations were evaluated during previous controlled cannabis administration studies following tandem alkaline/E. coli β-glucuronidase hydrolysis. We optimized recombinant β-glucuronidase enzymatic urinary hydrolysis before simultaneous liquid chromatography tandem mass spectrometry (LC-MS/MS) quantification of THC, 11-OH-THC, THCCOOH, cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), tetrahydrocannabivarin (THCV) and 11-nor-9-carboxy-THCV (THCVCOOH) in urine. Enzyme amount, incubation time and temperature, buffer molarity and pH were optimized using pooled urine samples collected during a National Institute on Drug Abuse, Institutional Review Board-approved clinical study. Optimized cannabinoid hydrolysis with recombinant β-glucuronidase was achieved with 2000 IU enzyme, 2 M pH 6.8 sodium phosphate buffer, and 0.2 mL urine at 37°C for 16 h. The LC-MS/MS quantification method for hydrolyzed urinary cannabinoids was validated per the Scientific Working Group on Toxicology guidelines. Linear ranges were 1-250 μg/L for THC and CBG, 2-250 μg/L for 11-OH-THC, CBD, CBN, THCV and THCVCOOH, and 1-500 μg/L for THCCOOH. Inter-batch analytical bias was 92.4-112.4%, imprecision 4.4-9.3% CV (n = 25), extraction efficiency 44.3-97.1% and matrix effect -29.6 to 1.8% (n = 10). The method was utilized to analyze urine specimens collected during our controlled smoked, vaporized, and edible cannabis administration study to improve interpretation of urine cannabinoid test results. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

The Colour Test for drug susceptibility testing of Mycobacterium tuberculosis strains.

PubMed

Toit, K; Mitchell, S; Balabanova, Y; Evans, C A; Kummik, T; Nikolayevskyy, V; Drobniewski, F

2012-08-01

Tartu, Estonia. To assess the performance and feasibility of the introduction of the thin-layer agar MDR/XDR-TB Colour Test (Colour Test) as a non-commercial method of drug susceptibility testing (DST). The Colour Test combines the thin-layer agar technique with a simple colour-coded quadrant format, selective medium to reduce contamination and colorimetric indication of bacterial growth to simplify interpretation. DST patterns for isoniazid (INH), rifampicin (RMP) and ciprofloxacin (CFX) were determined using the Colour Test for 201 archived Mycobacterium tuberculosis isolates. Susceptibilities were compared to blinded DST results obtained routinely using the BACTEC™ Mycobacteria Growth Indicator Tube™ (MGIT) 960 to assess performance characteristics. In all, 98% of the isolates produced interpretable results. The average time to positivity was 13 days, and all results were interpretable. The Colour Test detected drug resistance with 98% sensitivity for INH, RMP and CFX and 99% for multidrug-resistant tuberculosis. Specificities were respectively 100% (95%CI 82-100), 88% (95%CI 69-97) and 91% (95%CI 83-96) and 90% (95%CI 74-98). Agreement between the Colour Test and BACTEC MGIT 960 were respectively 98%, 96%, 94% and 97%. The Colour Test could be an economical, accurate and simple technique for testing tuberculosis strains for drug resistance. As it requires little specialist equipment, it may be particularly useful in resource-constrained settings with growing drug resistance rates.

Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms.

PubMed

Morrison, Paul D; Nottage, Judith; Stone, James M; Bhattacharyya, Sagnik; Tunstall, Nigel; Brenneisen, Rudolf; Holt, David; Wilson, Daniel; Sumich, Alex; McGuire, Philip; Murray, Robin M; Kapur, Shitij; Ffytche, Dominic H

2011-03-01

The main ingredient in cannabis, Δ(9)-tetrahydrocannabinol (THC), can elicit acute psychotic reactions in healthy individuals and precipitate relapse in schizophrenic patients. However, the neural mechanism of this is unknown. We tested the hypothesis that THC psychopathology is related to changes in electroencephalography (EEG) power or inter-regional coherence. In a within-subjects design, participants (n=16) were given intravenous THC (1.25 mg) or placebo under double-blind conditions, during EEG recordings. Using fast-Fourier transform, EEG data were analyzed for power and coherence in the delta (1-3.5 Hz), theta (3.5-7 Hz), alpha (8-13 Hz), beta (14-25 Hz), low-gamma (30-40 Hz), and high-gamma (60-70 Hz) bands during engagement in the n-back test of working memory (WM). Compared with placebo, THC evoked positive and negative psychotic symptoms, as measured by the positive and negative syndrome scale (p<0.001) and slowed WM performance (p<0.05). Under THC, theta power was specifically reduced, (p<0.001) regardless of WM load; however, the reduction showed no relationship with psychotic symptoms or WM impairment. Coherence between bi-frontal electrodes in the theta band was also reduced by THC (p<0.05) and these reductions correlated with the change-in positive psychotic symptoms (rho=0.79, p<0.001). Bi-frontal specificity was suggested by the absence of a relationship between psychotic symptoms and fronto-parietal coherence. The results reveal that the pro-psychotic effects of THC might be related to impaired network dynamics with impaired communication between the right and left frontal lobes.

Recovery of spiked Δ9-tetrahydrocannabinol in oral fluid from polypropylene containers.

PubMed

Molnar, Anna; Lewis, John; Fu, Shanlin

2013-04-10

Oral fluid is currently used by Australian and international law enforcement agencies and employers to detect recent use of cannabis and other drugs of abuse. The main psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol (THC), is highly lipophilic and losses occur when in contact with plastic, possibly due to its adsorption onto the plastic surface. This study aims to investigate factors governing the interaction of THC with plastic and search for ways of overcoming such interaction so to improve THC recovery. As polypropylene is one of the most common types of plastic used in collection devices, it was the focus of this study. All experiments were done by preparing neat oral fluid samples spiked with THC in 2-mL polypropylene centrifuge tubes. Samples were transferred with or without prior addition of Triton(®) X-100 (0.25%) to glass tubes containing d3-THC as internal standard and 0.1M phosphate buffer was then added. Samples were extracted by liquid-liquid extraction using hexane/ethyl acetate (9:1, v/v), dried and analysed by gas chromatography-mass spectrometry (GC-MS) after derivatisation. No significant difference was found in terms of THC loss to plastic when the concentration ranged from 25 to 1000 ng/mL in the same volume of oral fluid. Varying the oral fluid volume (0.5-1.5 mL) while keeping THC at a constant concentration showed an upward trend with more loss associated with lower volumes. The use of Triton(®) X-100 significantly decreased the adherence of THC to the plastic tubes and increased the THC transfer (>96%) at all volumes tested. Degradation of THC during storage was also studied over a 4-week period and it was found that azide did not seem to play a significant role in preserving THC in oral fluid. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

40 CFR 63.2262 - How do I conduct performance tests and establish operating requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... or documentation of inlet methanol or formaldehyde concentration is required) and outlet of the... HAP, formaldehyde, methanol, or total hydrocarbon (THC) emission rates. (2) When showing compliance... acetaldehyde, acrolein, formaldehyde, methanol, phenol, and propionaldehyde), THC, formaldehyde, or methanol in...

40 CFR 63.2262 - How do I conduct performance tests and establish operating requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

... or documentation of inlet methanol or formaldehyde concentration is required) and outlet of the... HAP, formaldehyde, methanol, or total hydrocarbon (THC) emission rates. (2) When showing compliance... acetaldehyde, acrolein, formaldehyde, methanol, phenol, and propionaldehyde), THC, formaldehyde, or methanol in...

Visual search and urban driving under the influence of marijuana and alcohol.

PubMed

Lamers, C. T. J.; Ramaekers, J. G.

2001-07-01

The purpose of the present study was to assess the effects of low doses of marijuana and alcohol, and their combination, on visual search at intersections and on general driving proficiency in the City Driving Test. Sixteen recreational users of alcohol and marijuana (eight males and eight females) were treated with these substances or placebo according to a balanced, 4-way, cross-over, observer- and subject-blind design. On separate evenings, subjects received weight-calibrated doses of THC, alcohol or placebo in each of the following treatment conditions: alcohol placebo + THC placebo, alcohol + THC placebo, THC 100 &mgr;g/kg + alcohol placebo, THC 100 &mgr;g/kg + alcohol. Alcohol doses administered were sufficient for achieving a blood alcohol concentration (BAC) of about 0.05 g/dl. Initial drinking preceded smoking by one hour. The City Driving Test commenced 15 minutes after smoking and lasted 45 minutes. The test was conducted over a fixed route within the city limits of Maastricht. An eye movement recording system was mounted on each subject's head for providing relative frequency measures of appropriate visual search at intersections. General driving quality was rated by a licensed driving instructor on a shortened version of the Royal Dutch Tourist Association's Driving Proficiency Test. After placebo treatment subjects searched for traffic approaching from side streets on the right in 84% of all cases. Visual search frequency in these subjects did not change when they were treated with alcohol or marijuana alone. However, when treated with the combination of alcohol and marijuana, the frequency of visual search dropped by 3%. Performance as rated on the Driving Proficiency Scale did not differ between treatments. It was concluded that the effects of low doses of THC (100 &mgr;g/kg) and alcohol (BAC < 0.05 g/dl) on higher-level driving skills as measured in the present study are minimal. Copyright 2001 John Wiley & Sons, Ltd.

Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

PubMed

Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

2014-07-15

Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival

PubMed Central

Marcu, Jahan P.; Christian, Rigel T.; Lau, Darryl; Zielinski, Anne J.; Horowitz, Maxx P.; Lee, Jasmine; Pakdel, Arash; Allison, Juanita; Limbad, Chandani; Moore, Dan H.; Yount, Garret L.; Desprez, Pierre-Yves; McAllister, Sean D.

2009-01-01

The cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor agonist, Δ9-tetrahydrocannabinol (THC), has been shown to be a broad range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB1 and CB2 receptors, can modulate the actions of Δ9-THC. However, there are conflicting reports as to what extent other cannabinoids can modulate Δ9-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Δ9-THC. We therefore tested cannabidiol (CBD), the second most abundant plant derived cannabiniod, in combination with Δ9-THC. In U251 and SF126 glioblastoma cell lines, Δ9-THC and CBD acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species (ROS) and apoptosis as well as specific modulations of extracellular signal-regulated kinase (ERK) and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of CBD to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients. PMID:20053780

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.

Disruption in the autophagic process underlies the sensory neuropathy in dystonia musculorum mice.

PubMed

Ferrier, Andrew; De Repentigny, Yves; Lynch-Godrei, Anisha; Gibeault, Sabrina; Eid, Walaa; Kuo, Daniel; Zha, Xiaohui; Kothary, Rashmi

2015-01-01

A homozygous mutation in the DST (dystonin) gene causes a newly identified lethal form of hereditary sensory and autonomic neuropathy in humans (HSAN-VI). DST loss of function similarly leads to sensory neuron degeneration and severe ataxia in dystonia musculorum (Dst(dt)) mice. DST is involved in maintaining cytoskeletal integrity and intracellular transport. As autophagy is highly reliant upon stable microtubules and motor proteins, we assessed the influence of DST loss of function on autophagy using the Dst(dt-Tg4) mouse model. Electron microscopy (EM) revealed an accumulation of autophagosomes in sensory neurons from these mice. Furthermore, we demonstrated that the autophagic flux was impaired. Levels of LC3-II, a marker of autophagosomes, were elevated. Consequently, Dst(dt-Tg4) sensory neurons displayed impaired protein turnover of autophagosome substrate SQTSM1/p62 and of polyubiquitinated proteins. Interestingly, in a previously described Dst(dt-Tg4) mouse model that is partially rescued by neuronal specific expression of the DST-A2 isoform, autophagosomes, autolysosomes, and damaged organelles were reduced when compared to Dst(dt-Tg4) mutant mice. LC3-II, SQTSM1, polyubiquitinated proteins and autophagic flux were also restored to wild-type levels in the rescued mice. Finally, a significant decrease in DNAIC1 (dynein, axonemal, intermediate chain 1; the mouse ortholog of human DNAI1), a member of the DMC (dynein/dynactin motor complex), was noted in Dst(dt-Tg4) dorsal root ganglia and sensory neurons. Thus, DST-A2 loss of function perturbs late stages of autophagy, and dysfunctional autophagy at least partially underlies Dst(dt) pathogenesis. We therefore conclude that the DST-A2 isoform normally facilitates autophagy within sensory neurons to maintain cellular homeostasis.

Interpretation of Cannabis Findings in the Hair of Very Young Children: Mission Impossible.

PubMed

Kintz, Pascal; Ameline, Alice; Eibel, Aude; Gheddar, Laurie; Feisthauer, Emilie; Geraut, Annie; Berthelon, Laurent; Farrugia, Audrey; Raul, Jean-Sebastien

2017-01-01

Hair has been suggested since the middle of the 90's to be a suitable matrix to document repetitive exposure to cannabis. Because it is possible to detect Δ9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) in cannabis smoke, the identification of the metabolite, 11-nor-Δ9-tetrahydrocannabinol carboxylic acid (THC-COOH) has been considered to allow the discrimination of active use. Although the identification of an active compound in a child's hair shows contamination of the local environment, it is a challenge to discriminate between hair incorporation after ingestion or inhalation and environmental external deposition from dust, smoke, or even contaminated surfaces by hand contact. However, it is particularly important in case of children to correctly interpret the data, particularly for a realistic assessment of the health risk. We present here a series of hair tests for cannabis where the interpretation was almost impossible to establish. Hair specimens were collected during the autopsy of the 12 children, aged 2 to 24 months, either deceased from shaken baby syndrome (SBS, n=4), mechanic asphyxia (MA, n=1) or sudden infant death (SID, n=7) during January 2015 to April 2017. After decontamination, the hair specimens were tested for THC, CBN and CBD and THC-COOH. The whole length of hair was submitted to analysis. The amount of hair from children can be as low as 8 mg. This may affect the limit of quantitation of all drugs, but particularly THC-COOH. Eight from twelve hair tests were positive for cannabis markers, i.e. THC (39 to 1890 pg/mg, n=8), CBN (< 5 to 1300 pg/mg n=8), CBD (10 to 2300 pg/mg, n=8) and THC-COOH (not detected to < 0.5 pg/mg, n=5). In 4 cases from 8 positive findings, it was not possible to test for THC-COOH (not enough material). Establishing a window of detection when testing for drugs in young children is a very complicated task. Hair from children is finer and more porous in comparison with adult (the risk of contamination from sweat and environmental smoke is higher than in adults). The final interpretation of cannabinoid findings in the children's hair is very complicated as this can result from in utero exposure (although none of the mother admitted cannabis use during pregnancy), oral cannabis administration by the parents to achieve sedation, close contact to cannabis consumers (hands, bedding, dishes) and inhalation of side-stream smoke. Over-interpreting cannabis findings in hair can have very serious legal implication in child protection cases. Practicing scientists have the responsibility to inform the child protection authorities, courts, etc. about these limitations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Cannabinoid facilitation of fear extinction memory recall in humans

PubMed Central

Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Abelson, James L.; Liberzon, Israel; Milad, Mohammed R.; Phan, K. Luan

2012-01-01

A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 hours prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 hours after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 hours after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. PMID:22796109

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

PubMed

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol.

Development and validation of an automated liquid-liquid extraction GC/MS method for the determination of THC, 11-OH-THC, and free THC-carboxylic acid (THC-COOH) from blood serum.

PubMed

Purschke, Kirsten; Heinl, Sonja; Lerch, Oliver; Erdmann, Freidoon; Veit, Florian

2016-06-01

The analysis of Δ(9)-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-Δ(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH) from blood serum is a routine task in forensic toxicology laboratories. For examination of consumption habits, the concentration of the phase I metabolite THC-COOH is used. Recommendations for interpretation of analysis values in medical-psychological assessments (regranting of driver's licenses, Germany) include threshold values for the free, unconjugated THC-COOH. Using a fully automated two-step liquid-liquid extraction, THC, 11-OH-THC, and free, unconjugated THC-COOH were extracted from blood serum, silylated with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA), and analyzed by GC/MS. The automation was carried out by an x-y-z sample robot equipped with modules for shaking, centrifugation, and solvent evaporation. This method was based on a previously developed manual sample preparation method. Validation guidelines of the Society of Toxicological and Forensic Chemistry (GTFCh) were fulfilled for both methods, at which the focus of this article is the automated one. Limits of detection and quantification for THC were 0.3 and 0.6 μg/L, for 11-OH-THC were 0.1 and 0.8 μg/L, and for THC-COOH were 0.3 and 1.1 μg/L, when extracting only 0.5 mL of blood serum. Therefore, the required limit of quantification for THC of 1 μg/L in driving under the influence of cannabis cases in Germany (and other countries) can be reached and the method can be employed in that context. Real and external control samples were analyzed, and a round robin test was passed successfully. To date, the method is employed in the Institute of Legal Medicine in Giessen, Germany, in daily routine. Automation helps in avoiding errors during sample preparation and reduces the workload of the laboratory personnel. Due to its flexibility, the analysis system can be employed for other liquid-liquid extractions as well. To the best of our knowledge, this is the first publication on a comprehensively automated classical liquid-liquid extraction workflow in the field of forensic toxicological analysis. Graphical abstract GC/MS with MPS Dual Head at the Institute of Legal Medicine, Giessen, Germany. Modules from left to right: (quick) Mix (for LLE), wash station, tray 1 (vials for extracts), solvent reservoir, (m) VAP (for extract evaporation), Solvent Filling Station (solvent supply), cooled tray 2 (vials for serum samples), and centrifuge (for phase separation).

40 CFR Table 5 to Subpart Dddd of... - Performance Testing and Initial Compliance Demonstrations for the Compliance Options and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Table 1B to this subpart Reduce emissions of total HAP, measured as THC, by 90 percent Total HAP... 1B to this subpart Limit emissions of total HAP, measured as THC, to 20 ppmvd The average total HAP...

40 CFR Table 5 to Subpart Dddd of... - Performance Testing and Initial Compliance Demonstrations for the Compliance Options and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Table 1B to this subpart Reduce emissions of total HAP, measured as THC, by 90 percent Total HAP... 1B to this subpart Limit emissions of total HAP, measured as THC, to 20 ppmvd The average total HAP...

Phenotypic and genotypic analysis of anti-tuberculosis drug resistance in Mycobacterium tuberculosis isolates in Myanmar.

PubMed

Aung, Wah Wah; Ei, Phyu Win; Nyunt, Wint Wint; Swe, Thyn Lei; Lwin, Thandar; Htwe, Mi Mi; Kim, Kyung Jun; Lee, Jong Seok; Kim, Chang Ki; Cho, Sang Nae; Song, Sun Dae; Chang, Chulhun L

2015-09-01

Tuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar. We determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid). Of 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01). The results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

PubMed Central

Tran, Huong Thi Giang; Bui, Quyen Thi Tu

2016-01-01

Introduction Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Methods Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. Results A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. Conclusion This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance. PMID:27508089

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011.

PubMed

Nguyen, Hoa Binh; Nguyen, Nhung Viet; Tran, Huong Thi Giang; Nguyen, Hai Viet; Bui, Quyen Thi Tu

2016-01-01

Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

Potential market for novel tuberculosis diagnostics: worth the investment?

PubMed

Kik, Sandra V; Denkinger, Claudia M; Jefferson, Carole; Ginnard, Janet; Pai, Madhukar

2015-04-01

The potential available market (PAM) for new diagnostics for tuberculosis that meet the specifications of the high-priority target product profiles (TPPs) is currently unknown. We estimated the PAM in 2020 in 4 high-burden countries (South Africa, Brazil, China, and India) for tests that meet the specifications outlined in the TPPs. The yearly PAM was estimated for the most likely application of each TPP. In 2020 the PAM for all 4 countries together was estimated to be (1) 12M tests/year with a value of 48M-71M USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M-97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M tests/year for a DST that follows a positive tuberculosis detection test with a corresponding value of 75M-121M for both tuberculosis detection and DST. Although there is a considerable potential market for novel tuberculosis diagnostics that fit the specification of the TPPs in the 4 high-burden countries, the actual market for an individual product remains uncertain. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

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

Rifampicin Resistance and Multidrug-Resistant Tuberculosis Detection Using Xpert MTB/RIF in Wuhan, China: A Retrospective Study.

PubMed

Huang, Hai; Zhang, Yanlin; Li, Sheng; Wang, Jun; Chen, Jun; Pan, Zhiyun; Gan, Hui

2018-06-01

The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA) can simultaneously detect the Mycobacterium tuberculosis (MTB) complex DNA and rifampicin (RFP) resistance and can rapidly determine RFP resistance and predict multidrug-resistant tuberculosis (MDR-TB). In this study, we analyzed clinical examination results of a hospital specializing in TB treatment in Wuhan, Hubei, China, and examined the use of traditional culture and drug-sensitive test (DST) results as a gold standard to assess the diagnosis value of the Xpert MTB/RIF test in RFP resistance and MDR-TB. A total of 2,910 specimens were received in the Mycobacteriology Laboratory, Wuhan Pulmonary Hospital, for Xpert MTB/RIF testing between December 2013 and December 2014. After the results were reviewed by exclusion criteria, 1,066 Xpert test results were eligible for our study. We then compared the Xpert test results with sputum acid-fast bacilli staining, cultures, and DST results. In total, Xpert correctly identified 96.71% (147/152) RFP-resistant TB and 98.25% (898/914) RFP-sensitive TB specimens. Of the 147 RFP-resistant TB specimens detected by Xpert, 122 MDR-TB (82.99%) were identified by traditional culture and DST techniques. Xpert can simultaneously detect MTB and RFP resistance with high sensitivity and specificity. Thus, Xpert testing aids in saving a considerable amount of time in the diagnosis and treatment of MDR-TB.

Effects of 20 mg oral Δ9-tetrahydrocannabinol on the olfactory function of healthy volunteers*

PubMed Central

Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

2014-01-01

Aims Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ9-tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. Methods The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Results Δ9-Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, −7.8 to −2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Conclusions Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. PMID:24802974

Effects of 20 mg oral Δ(9) -tetrahydrocannabinol on the olfactory function of healthy volunteers.

PubMed

Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

2014-11-01

Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ(9) -tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Δ(9) -Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, -7.8 to -2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. © 2014 The British Pharmacological Society.

Hippocampal Protein Kinase C Signaling Mediates the Short-Term Memory Impairment Induced by Delta9-Tetrahydrocannabinol.

PubMed

Busquets-Garcia, Arnau; Gomis-González, Maria; Salgado-Mendialdúa, Victòria; Galera-López, Lorena; Puighermanal, Emma; Martín-García, Elena; Maldonado, Rafael; Ozaita, Andrés

2018-04-01

Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit. Immunoblot analysis revealed a transient increase in PKC signaling activity in the hippocampus after THC treatment. Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. This significant immunoreactive band that paralleled cognitive performance did not match in size with the major PKC isoforms expressed in the hippocampus except for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. These data demonstrate that THC alters short-term object-recognition memory through hippocampal PKC/neurogranin signaling.

Mysql Data-Base Applications for Dst-Like Physics Analysis

NASA Astrophysics Data System (ADS)

Tsenov, Roumen

2004-07-01

The data and analysis model developed and being used in the HARP experiment for studying hadron production at CERN Proton Synchrotron is discussed. Emphasis is put on usage of data-base (DB) back-ends for persistent storing and retrieving "alive" C++ objects encapsulating raw and reconstructed data. Concepts of "Data Summary Tape" (DST) as a logical collection of DB-persistent data of different types, and of "intermediate DST" (iDST) as a physical "tag" of DST, are introduced. iDST level of persistency allows a powerful, DST-level of analysis to be performed by applications running on an isolated machine (even laptop) with no connection to the experiment's main data storage. Implementation of these concepts is considered.

USGS 1-min Dst index

USGS Publications Warehouse

Gannon, J.L.; Love, J.J.

2011-01-01

We produce a 1-min time resolution storm-time disturbance index, the USGS Dst, called Dst8507-4SM. This index is based on minute resolution horizontal magnetic field intensity from low-latitude observatories in Honolulu, Kakioka, San Juan and Hermanus, for the years 1985-2007. The method used to produce the index uses a combination of time- and frequency-domain techniques, which more clearly identifies and excises solar-quiet variation from the horizontal intensity time series of an individual station than the strictly time-domain method used in the Kyoto Dst index. The USGS 1-min Dst is compared against the Kyoto Dst, Kyoto Sym-H, and the USGS 1-h Dst (Dst5807-4SH). In a time series comparison, Sym-H is found to produce more extreme values during both sudden impulses and main phase maximum deviation, possibly due to the latitude of its contributing observatories. Both Kyoto indices are shown to have a peak in their distributions below zero, while the USGS indices have a peak near zero. The USGS 1-min Dst is shown to have the higher time resolution benefits of Sym-H, while using the more typical low-latitude observatories of Kyoto Dst. ?? 2010.

Oral fluid cannabinoid concentrations following controlled smoked cannabis in chronic frequent and occasional smokers

PubMed Central

Anizan, Sebastien; Milman, Garry; Desrosiers, Nathalie; Barnes, Allan J.; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

Background Oral fluid (OF) is an alternative biological matrix for monitoring cannabis intake in drug testing, and drugged driving (DUID) programs, but OF cannabinoid test interpretation is challenging. Controlled cannabinoid administration studies provide a scientific database for interpreting cannabinoid OF tests. Methods We compared differences in OF cannabinoid concentrations from 19h before to 30h after smoking a 6.8% THC cigarette in chronic frequent and occasional cannabis smokers. OF was collected with the Statsure Saliva Sampler™ OF device. 2D-GC-MS was used to quantify cannabinoids in 357 OF specimens; 65 had inadequate OF volume within 3h after smoking. Results All OF specimens were THC-positive for up to 13.5h after smoking, without significant differences between frequent and occasional smokers over 30h. CBD and CBN had short median last detection times (2.5–4h for CBD and 6–8h for CBN) in both groups. THCCOOH was detected in 25 and 212 occasional and frequent smokers’ OF samples, respectively. THCCOOH provided longer detection windows than THC in all frequent smokers. As THCCOOH is not present in cannabis smoke, it’s presence in OF minimizes the potential for false positive results from passive environmental smoke exposure, and can identify oral THC ingestion, while OF THC cannot. THC≥1μg/L, in addition to CBD≥1μg/L or CBN≥1μg/L suggested recent cannabis intake (≤13.5h), important for DUID cases, whereas THC≥1μg/L or THC≥2μg/L cutoffs had longer detection windows (≥30h), important for workplace testing. THCCOOH windows of detection for chronic, frequent cannabis smokers extended beyond 30 h, while they were shorter (0–24h) for occasional cannabis smokers. PMID:23954944

The thin-layer agar method for direct phenotypic detection of multi- and extensively drug-resistant tuberculosis.

PubMed

Ardizzoni, E; Mulders, W; Kotrikadze, T; Aspindzelashvili, R; Goginashvili, L; Pangtey, H; Varaine, F; Bastard, M; Rigouts, L; de Jong, B C

2015-12-01

Molecular techniques rapidly detect resistance to rifampicin (RMP) and isoniazid (INH), but do not eliminate the need for culture-based drug susceptibility testing (DST) against other drugs. The thin-layer agar (TLA) test, a non-commercial direct DST method, has demonstrated good performance for INH and RMP; however, evidence is still limited, and its applicability for DST of ofloxacin (OFX) and kanamycin (KM) is unknown. We compared 279 TLA DST results with those of MGIT for INH and RMP, and 280 results for OFX and KM with those of the 7H11 agar proportion method, obtained from 320 smear-positive samples from 165 Georgian TB patients. Discrepancies were solved by comparison with a composite reference standard. The prevalence of multidrug-resistant tuberculosis (TB) was 30 of 164 patients (18.3%), 2 (6.7%) of whom had extensively drug-resistant TB. TLA showed 94.7%, 98.2%, 100% and 78.9% sensitivity, respectively, for INH, RMP, OFX and KM, with 100% specificity. Average time to results was 7 days in TLA, 23 in MGIT and 49 for 7H11 agar. In low-resource settings, TLA can be applied for the rapid detection of resistance to INH, RMP and fluoroquinolones. Further studies are necessary to improve sensitivity to KM and further assess its performance for OFX and other drugs and its applicability in field conditions.

Decreasing Medication Turnaround Time with Digital Scanning Technology in a Canadian Health Region

PubMed Central

Neville, Heather; Nodwell, Lisa; Alsharif, Sahar

2014-01-01

Background: Reducing medication turnaround time can improve efficiency, patient safety, and quality of care in the hospital setting. Digital scanning technology (DST) can be used to electronically transmit scanned prescriber orders to a pharmacy computer queue for verification and processing, which may help to improve medication turnaround time. Objectives: To evaluate medication turnaround time before and after implementation of DST for all medications and for antibiotics only. Methods: Medication turnaround times were evaluated retrospectively for periods before (June 6–10, 2011) and after (September 26–30, 2011) implementation of DST at 2 hospital sites in 1 health region. Medication turnaround time was defined as the time from composition of a medication order by the prescriber to its verification by the pharmacy (phase 1) and the time from prescriber composition to administration to the patient by a nurse (total). Median turnaround times were analyzed with SPSS software using the Mann–Whitney U test. Results: In total, 304 and 244 medication orders were audited before and after DST implementation, respectively. Median phase 1 turnaround time for all medications declined significantly, from 2 h 23 min before DST implementation to 1 h 33 min after DST implementation (p < 0.001). Antibiotics were also processed significantly faster (1 h 51 min versus 1 h 9 min, p = 0.015). However, total turnaround time for all medications did not differ significantly (5 h 15 min versus 5 h 0 min, p = 0.42). Conclusions: Implementation of DST was associated with a 50-min decrease in medication turnaround time for the period from when an order was prescribed to the time it was processed by the pharmacy. Regular evaluation of medication turnaround times is recommended to compare with benchmarks, to ensure that hospital standards are being met, and to measure the effects of policy changes and implementation of new technology on medication-use processes. PMID:25548397

Decreasing medication turnaround time with digital scanning technology in a canadian health region.

PubMed

Neville, Heather; Nodwell, Lisa; Alsharif, Sahar

2014-11-01

Reducing medication turnaround time can improve efficiency, patient safety, and quality of care in the hospital setting. Digital scanning technology (DST) can be used to electronically transmit scanned prescriber orders to a pharmacy computer queue for verification and processing, which may help to improve medication turnaround time. To evaluate medication turnaround time before and after implementation of DST for all medications and for antibiotics only. Medication turnaround times were evaluated retrospectively for periods before (June 6-10, 2011) and after (September 26-30, 2011) implementation of DST at 2 hospital sites in 1 health region. Medication turnaround time was defined as the time from composition of a medication order by the prescriber to its verification by the pharmacy (phase 1) and the time from prescriber composition to administration to the patient by a nurse (total). Median turnaround times were analyzed with SPSS software using the Mann-Whitney U test. In total, 304 and 244 medication orders were audited before and after DST implementation, respectively. Median phase 1 turnaround time for all medications declined significantly, from 2 h 23 min before DST implementation to 1 h 33 min after DST implementation (p < 0.001). Antibiotics were also processed significantly faster (1 h 51 min versus 1 h 9 min, p = 0.015). However, total turnaround time for all medications did not differ significantly (5 h 15 min versus 5 h 0 min, p = 0.42). Implementation of DST was associated with a 50-min decrease in medication turnaround time for the period from when an order was prescribed to the time it was processed by the pharmacy. Regular evaluation of medication turnaround times is recommended to compare with benchmarks, to ensure that hospital standards are being met, and to measure the effects of policy changes and implementation of new technology on medication-use processes.

In vitro maturation of immature thymocytes into immunocompetent T cells in the absence of direct thymic influence.

PubMed

Irlé, C; Piguet, P F; Vassalli, P

1978-07-01

Peanut lectin (PNL) binds to a majority of mouse thymocytes (Thc) in suspension. By using cell affinity chromatography on a column of anti-PNL antibody, Thc populations at least 96 percent pure in PNL + or - cells, as judged by immunofluorescence, were obtained. PNL(+) cells are rich in Thy 1 and poor in H(2) antigens, cortisone sensitive, unresponsive to phytohemagglutinin (PHA), and immunologically incompetent, as judged by mixed lymphocyte reaction, popliteal lymph node graft-versus-host assay, and by testing helper activity in a primary in vitro antibody response to sheep erythrocytes; the converse is true of PNL(-) cells. Thus, PNL(+) and (-) cells appear to correspond to cortical and medullary Thc, respectively, as previously suggested. In culture, PNL(+) Thc show poor viability and a weak proliferative response to concanavalin A (Con A), except when supernate (SUP) of 24 h Con A stimulated lymph node lymphocyte cultures, or irradiated lymph node cells, are added, in which cases a strong proliferative response to the mitogen is observed. A variety of control experiments showed that the proliferating cells did not result from preferential stimulation of a few contaminating PNL(-) Thc present in the PNL(+) Thc cultures. The blasts resulting from PNL(+) Thc proliferation display mitogen-induced cytotoxicity, and give rise to a population of medium-sized lymphocytes, mostly PNL(-), poor in Thy 1 and rich in H(2) antigens, PHA responsive, and immunologically competent in the above-mentioned assays. Fresh PNL(+) Thc responded in mixed lymphocyte reaction in the presence of SUP (lectin depleted) and since incubation in SUP alone did not confer reactivity on PNL(+) Thc, it appears therefore that (a) immature Thc possess alloantigen and mitogen-specific surface receptors but lack the capacity to respond by proliferation to receptor triggering without the help of extracellular factor(s) released by mature lymphoid cells stimulated by mitogens (b) cell division is associated with the acquisition of immunological responsiveness, characteristic of mature T lymphocytes. The implications of these findings for the ontogenesis of thymus-derived lymphocytes, and for the possible traffic of Thc within and from the thymus, are discussed.

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. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing. PMID:22334121

Passive cannabis smoke exposure and oral fluid testing. II. Two studies of extreme cannabis smoke exposure in a motor vehicle.

PubMed

Niedbala, R Sam; Kardos, Keith W; Fritch, Dean F; Kunsman, Kenneth P; Blum, Kristen A; Newland, Gregory A; Waga, Joe; Kurtz, Lisa; Bronsgeest, Matth; Cone, Edward J

2005-10-01

Two studies were conducted to determine if extreme passive exposure to cannabis smoke in a motor vehicle would produce positive results for delta-tetrahydrocannabinol (THC) in oral fluid. Passive exposure to cannabis smoke in an unventilated room has been shown to produce a transient appearance of THC in oral fluid for up to 30 min. However, it is well known that such factors as room size and extent of smoke exposure can affect results. Questions have also been raised concerning the effects of tobacco when mixed with marijuana and THC content. We conducted two passive cannabis studies under severe passive smoke exposure conditions in an unventilated eight-passenger van. Four passive subjects sat alongside four active cannabis smokers who each smoked a single cannabis cigarette containing either 5.4%, 39.5 mg THC (Study 1) or 10.4%, 83.2 mg THC (Study 2). The cigarettes in Study 1 contained tobacco mixed with cannabis; cigarettes in Study 2 contained only cannabis. Oral fluid specimens were collected from passive and active subjects with the Intercept Oral Specimen Collection Device for 1 h after smoking cessation while inside the van (Study 1) and up to 72 h (passive) or 8 h (active) outside the van. Additionally in Study 1, Intercept collectors were exposed to smoke in the van to assess environmental contamination during collection procedures. For Study 2, all oral fluid collections were outside the van following smoking cessation to minimize environmental contamination. Oral samples were analyzed with the Cannabinoids Intercept MICRO-PLATE EIA and quantitatively by gas chromatography-tandem mass spectrometry (GC-MS-MS). THC concentrations were adjusted for dilution (x 3). The screening and confirmation cutoff concentrations for THC in neat oral fluid were 3 ng/mL and 1.5 ng/mL, respectively. The limits of detection (LOD) and quantitation (LOQ) for THC in the GC-MS-MS assay were 0.3 and 0.75 ng/mL, respectively. Urine specimens were collected, screened (EMIT, 50 ng/mL cutoff), and analyzed by GC-MS-MS for THCCOOH (LOD/LOQ = 1.0 ng/mL). Peak oral fluid THC concentrations in passive subjects recorded at the end of cannabis smoke exposure were up to 7.5 ng/mL (Study 1) and 1.2 ng/mL (Study 2). Thereafter, THC concentrations quickly declined to negative levels within 30-45 min in Study 1. It was found that environmentally exposed Collectors contained 3-14 ng/mL in Study 1. When potential contamination during collection was eliminated in Study 2, all passive subjects were negative at screening/confirmation cutoff concentrations throughout the study. Oral fluid specimens from active smokers had peak concentrations of THC approximately 100-fold greater than passive subjects in both studies. Positive oral fluid results were observed for active smokers 0-8 h. Urine analysis confirmed oral fluid results. These studies clarify earlier findings on the effects of passive cannabis smoke on oral fluid results. Oral fluid specimens collected in the presence of cannabis smoke appear to have been contaminated, thereby falsely elevating THC concentrations in oral fluid. The risk of a positive test for THC was virtually eliminated when specimens were collected in the absence of THC smoke.

40 CFR Table 5 to Subpart Dddd of... - Performance Testing and Initial Compliance Demonstrations for the Compliance Options and...

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Process unit listed in Table 1B to this subpart Reduce emissions of total HAP, measured as THC, by 90... listed in Table 1B to this subpart Limit emissions of total HAP, measured as THC, to 20 ppmvd The average...

40 CFR Table 5 to Subpart Dddd of... - Performance Testing and Initial Compliance Demonstrations for the Compliance Options and...

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Process unit listed in Table 1B to this subpart Reduce emissions of total HAP, measured as THC, by 90... listed in Table 1B to this subpart Limit emissions of total HAP, measured as THC, to 20 ppmvd The average...

40 CFR Table 5 to Subpart Dddd of... - Performance Testing and Initial Compliance Demonstrations for the Compliance Options and...

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Process unit listed in Table 1B to this subpart Reduce emissions of total HAP, measured as THC, by 90... listed in Table 1B to this subpart Limit emissions of total HAP, measured as THC, to 20 ppmvd The average...

HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients.

PubMed

Jokinen, Jussi; Nordström, Peter

2009-07-01

Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Combined Species Identification and Drug Sensitivity Testing in Mycobacteria.

PubMed

Ceyssens, Pieter-Jan; Soetaert, Karine; Timke, Markus; Van den Bossche, An; Sparbier, Katrin; De Cremer, Koen; Kostrzewa, Markus; Hendrickx, Marijke; Mathys, Vanessa

2017-02-01

Species identification and drug susceptibility testing (DST) of mycobacteria are important yet complex processes traditionally reserved for reference laboratories. Recent technical improvements in matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has started to facilitate routine mycobacterial identifications in clinical laboratories. In this paper, we investigate the possibility of performing phenotypic MALDI-based DST in mycobacteriology using the recently described MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA). We randomly selected 72 clinical Mycobacterium tuberculosis and nontuberculous mycobacterial (NTM) strains, subjected them to MBT-ASTRA methodology, and compared its results to current gold-standard methods. Drug susceptibility was tested for rifampin, isoniazid, linezolid, and ethambutol (M. tuberculosis, n = 39), and clarithromycin and rifabutin (NTM, n = 33). Combined species identification was performed using the Biotyper Mycobacteria Library 4.0. Mycobacterium-specific MBT-ASTRA parameters were derived (calculation window, m/z 5,000 to 13,000, area under the curve [AUC] of >0.015, relative growth [RG] of <0.5; see the text for details). Using these settings, MBT-ASTRA analyses returned 175/177 M. tuberculosis and 65/66 NTM drug resistance profiles which corresponded to standard testing results. Turnaround times were not significantly different in M. tuberculosis testing, but the MBT-ASTRA method delivered on average a week faster than routine DST in NTM. Databases searches returned 90.4% correct species-level identifications, which increased to 98.6% when score thresholds were lowered to 1.65. In conclusion, the MBT-ASTRA technology holds promise to facilitate and fasten mycobacterial DST and to combine it directly with high-confidence species-level identifications. Given the ease of interpretation, its application in NTM typing might be the first in finding its way to current diagnostic workflows. However, further validations and automation are required before routine implementation can be envisioned. Copyright © 2017 American Society for Microbiology.

Idle emissions from heavy-duty diesel and natural gas vehicles at high altitude.

PubMed

McCormick, R L; Graboski, M S; Alleman, T L; Yanowitz, J

2000-11-01

Idle emissions of total hydrocarbon (THC), CO, NOx, and particulate matter (PM) were measured from 24 heavy-duty diesel-fueled (12 trucks and 12 buses) and 4 heavy-duty compressed natural gas (CNG)-fueled vehicles. The volatile organic fraction (VOF) of PM and aldehyde emissions were also measured for many of the diesel vehicles. Experiments were conducted at 1609 m above sea level using a full exhaust flow dilution tunnel method identical to that used for heavy-duty engine Federal Test Procedure (FTP) testing. Diesel trucks averaged 0.170 g/min THC, 1.183 g/min CO, 1.416 g/min NOx, and 0.030 g/min PM. Diesel buses averaged 0.137 g/min THC, 1.326 g/min CO, 2.015 g/min NOx, and 0.048 g/min PM. Results are compared to idle emission factors from the MOBILE5 and PART5 inventory models. The models significantly (45-75%) overestimate emissions of THC and CO in comparison with results measured from the fleet of vehicles examined in this study. Measured NOx emissions were significantly higher (30-100%) than model predictions. For the pre-1999 (pre-consent decree) truck engines examined in this study, idle NOx emissions increased with model year with a linear fit (r2 = 0.6). PART5 nationwide fleet average emissions are within 1 order of magnitude of emissions for the group of vehicles tested in this study. Aldehyde emissions for bus idling averaged 6 mg/min. The VOF averaged 19% of total PM for buses and 49% for trucks. CNG vehicle idle emissions averaged 1.435 g/min for THC, 1.119 g/min for CO, 0.267 g/min for NOx, and 0.003 g/min for PM. The g/min PM emissions are only a small fraction of g/min PM emissions during vehicle driving. However, idle emissions of NOx, CO, and THC are significant in comparison with driving emissions.

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

PubMed

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

2015-12-01

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

Distribution of ∆(9)-Tetrahydrocannabinol and 11-Nor-9-Carboxy-∆(9)-Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents.

PubMed

Kemp, Philip M; Cardona, Patrick S; Chaturvedi, Arvind K; Soper, John W

2015-07-01

Little is known of the postmortem distribution of ∆(9)-tetrahydrocannabinol (THC) and its major metabolite, 11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THCCOOH). Data from 55 pilots involved in fatal aviation accidents are presented in this study. Gas chromatography/mass spectrometry analysis obtained mean THC concentrations in blood from multiple sites, liver, lung, and kidney of 15.6 ng/mL, 92.4 ng/g, 766.0 ng/g, 44.1 ng/g and mean THCCOOH concentrations of 35.9 ng/mL, 322.4 ng/g, 42.6 ng/g, 138.5 ng/g, respectively. Heart THC concentrations (two cases) were 184.4 and 759.3 ng/g, and corresponding THCCOOH measured 11.0 and 95.9 ng/g, respectively. Muscle concentrations for THC (two cases) were 16.6 and 2.5 ng/g; corresponding THCCOOH, "confirmed positive" and 1.4 ng/g. The only brain tested in this study showed no THC detected and 2.9 ng/g THCCOOH, low concentrations that correlated with low values in other specimens from this case. This research emphasizes the need for postmortem cannabinoid testing and demonstrates the usefulness of a number of tissues, most notably lung, for these analyses. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Collagen gel droplet-embedded culture drug sensitivity testing in squamous cell carcinoma cell lines derived from human oral cancers: Optimal contact concentrations of cisplatin and fluorouracil.

PubMed

Sakuma, Kaname; Tanaka, Akira; Mataga, Izumi

2016-12-01

The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that uses a method of three-dimensional culture of extremely small samples, and it is suited to primary cultures of human cancer cells. It is a useful method for oral squamous cell carcinoma (OSCC), in which the cancer tissues available for testing are limited. However, since the optimal contact concentrations of anticancer drugs have yet to be established in OSCC, CD-DST for detecting drug sensitivities of OSCC is currently performed by applying the optimal contact concentrations for stomach cancer. In the present study, squamous carcinoma cell lines from human oral cancer were used to investigate the optimal contact concentrations of cisplatin (CDDP) and fluorouracil (5-FU) during CD-DST for OSCC. CD-DST was performed in 7 squamous cell carcinoma cell lines derived from human oral cancers (Ca9-22, HSC-3, HSC-4, HO-1-N-1, KON, OSC-19 and SAS) using CDDP (0.15, 0.3, 1.25, 2.5, 5.0 and 10.0 µg/ml) and 5-FU (0.4, 0.9, 1.8, 3.8, 7.5, 15.0 and 30.0 µg/ml), and the optimal contact concentrations were calculated from the clinical response rate of OSCC to single-drug treatment and the in vitro efficacy rate curve. The optimal concentrations were 0.5 µg/ml for CDDP and 0.7 µg/ml for 5-FU. The antitumor efficacy of CDDP at this optimal contact concentration in CD-DST was compared to the antitumor efficacy in the nude mouse method. The T/C values, which were calculated as the ratio of the colony volume of the treatment group and the colony volume of the control group, at the optimal contact concentration of CDDP and of the nude mouse method were almost in agreement (P<0.05) and predicted clinical efficacy, indicating that the calculated optimal contact concentration is valid. Therefore, chemotherapy for OSCC based on anticancer drug sensitivity tests offers patients a greater freedom of choice and is likely to assume a greater importance in the selection of treatment from the perspectives of function preservation and quality of life, as well as representing a treatment option for unresectable, intractable or recurrent cases.

Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters.

PubMed

Ambrus, Livia; Lindqvist, Daniel; Träskman-Bendz, Lil; Westrin, Åsa

2016-11-01

Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items 'Concentration difficulties' and 'Failing memory' were extracted. Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = -0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = -0.372, p = 0.020). The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.

Assessment of the Microbial Control Measures for the Temperature and Humidity Control Subsystem Condensing Heat Exchanger of the International Space Station

NASA Technical Reports Server (NTRS)

Roman, Monsi C.; Steele, John W.; Marsh, Robert W.; Callahan, David M.; VonJouanne, Roger G.

1999-01-01

In August 1997 NASA/ Marshall Space Flight Center (MSFC) began a test with the objective of monitoring the growth of microorganisms on material simulating the surface of the International Space Station (ISS) Temperature and Humidity Control (THC) Condensing Heat Exchanger (CHX). The test addressed the concerns of potential uncontrolled microbial growth on the surface of the THC CHX subsystem. For this study, humidity condensate from a closed manned environment was used as a direct challenge to the surfaces of six cascades in a test set-up. The condensate was collected using a Shuttle-type CHX within the MSFC End-Use Equipment Testing Facility. Panels in four of the six cascades tested were coated with the ISS CHX silver impregnated hydrophilic coating. The remainder two cascade panels were coated with the hydrophilic coating without the antimicrobial component, silver. Results of the fourteen-month study are discussed in this paper. The effects on the microbial population when drying vs. not-drying the simulated THC CHX surface are also discussed.

Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.

PubMed

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

2014-04-01

Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge. Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH. During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking. The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.

Plasma Cannabinoid Concentrations during Dronabinol Pharmacotherapy for Cannabis Dependence

PubMed Central

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

2013-01-01

Background Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic daily cannabis smokers who received high-dose oral THC pharmacotherapy and later, a smoked cannabis challenge. Methods 11 daily cannabis smokers received 0, 30, 60, or 120 mg/day THC for four 5-day medication sessions, each separated by 9-days of ad-libitum cannabis smoking. On the 5th day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the 1st and 5th days was quantified by GC-GC-MS for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5–100 for THC, 1–50 11-OH-THC, and 0.5–200 THCCOOH. Results During placebo dosing, THC, 11-OH-THC and THCCOOH concentrations consistently decreased, while all cannabinoids increased dose-dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during 60 and 120 mg/day doses, and THCCOOH increased significantly only during the 120 mg/day dose. THC and 11-OH-THC, and THCCOOH concentrations peaked within 0.25 h after cannabis smoking, except after 120 mg/day THC when THCCOOH peaked 0.5 h before smoking. Conclusions The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 h, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 h after overnight oral dronabinol abstinence, but cannot distinguish oral THC dosing from smoked cannabis intake. PMID:24067260

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects

PubMed Central

Cone, Edward J.; Bigelow, George E.; Herrmann, Evan S.; Mitchell, John M.; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

2015-01-01

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ9-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC–MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC–MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. PMID:26139312

Cannabinoid Disposition in Oral Fluid after Controlled Smoked Cannabis

PubMed Central

Lee, Dayong; Schwope, David M.; Milman, Garry; Barnes, Allan J.; Gorelick, David A.; Huestis, Marilyn A.

2013-01-01

BACKGROUND We measured Δ9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) disposition in oral fluid (OF) following controlled cannabis smoking to evaluate whether monitoring multiple cannabinoids in OF improved OF test interpretation. METHODS Cannabis smokers provided written informed consent for this institutional review board–approved study. OF was collected with the Quantisal™ device following ad libitum smoking of one 6.8% THC cigarette. Cannabinoids were quantified by 2-dimensional GC-MS. We evaluated 8 alternative cutoffs based on different drug testing program needs. RESULTS 10 participants provided 86 OF samples −0.5 h before and 0.25, 0.5, 1, 2, 3, 4, 6, and 22 h after initiation of smoking. Before smoking, OF samples of 4 and 9 participants were positive for THC and THCCOOH, respectively, but none were positive for CBD and CBN. Maximum THC, CBD, and CBN concentrations occurred within 0.5 h, with medians of 644, 30.4, and 49.0 μg/L, respectively. All samples were THC positive at 6 h (2.1–44.4 μg/L), and 4 of 6 were positive at 22 h. CBD and CBN were positive only up to 6 h in 3 (0.6–2.1 μg/L) and 4 (1.0–4.4 μg/L) participants, respectively. The median maximum THCCOOH OF concentration was 115 ng/L, with all samples positive to 6 h (14.8–263 ng/L) and 5 of 6 positive at 22 h. CONCLUSIONS By quantifying multiple cannabinoids and evaluating different analytical cutoffs after controlled cannabis smoking, we determined windows of drug detection, found suggested markers of recent smoking, and minimized the potential for passive contamination. PMID:22273566

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.

Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ(9) tetrahydrocannabinol.

PubMed

Wright, M Jerry; Vandewater, Sophia A; Taffe, Michael A

2013-12-01

Recent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ(9) tetrahydrocannabinol (THC) content. Self-selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship. In this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self-Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg(-1) , i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg(-1) CBD. CBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self-Ordered Spatial Search task of working memory. CBD did not significantly reverse THC-induced impairment of a progressive ratio or a rotating turntable task. This study provides direct evidence that CBD can oppose the cognitive-impairing effects of THC and that it does so in a task-selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing therapeutic products may therefore help to ameliorate unwanted cognitive side-effects. This article is commented on by Mechoulam and Parker, pp 1363-1364 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12400. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

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.

Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response.

PubMed

McKallip, Robert J; Nagarkatti, Mitzi; Nagarkatti, Prakash S

2005-03-15

In the current study, we tested the central hypothesis that exposure to Delta-9-tetrahydrocannabinol (Delta9-THC), the major psychoactive component in marijuana, can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. We demonstrated that the human breast cancer cell lines MCF-7 and MDA-MB-231 and the mouse mammary carcinoma 4T1 express low to undetectable levels of cannabinoid receptors, CB1 and CB2, and that these cells are resistant to Delta9-THC-induced cytotoxicity. Furthermore, exposure of mice to Delta9-THC led to significantly elevated 4T1 tumor growth and metastasis due to inhibition of the specific antitumor immune response in vivo. The suppression of the antitumor immune response was mediated primarily through CB2 as opposed to CB1. Furthermore, exposure to Delta9-THC led to increased production of IL-4 and IL-10, suggesting that Delta9-THC exposure may specifically suppress the cell-mediated Th1 response by enhancing Th2-associated cytokines. This possibility was further supported by microarray data demonstrating the up-regulation of a number of Th2-related genes and the down-regulation of a number of Th1-related genes following exposure to Delta9-THC. Finally, injection of anti-IL-4 and anti-IL-10 mAbs led to a partial reversal of the Delta9-THC-induced suppression of the immune response to 4T1. Such findings suggest that marijuana exposure either recreationally or medicinally may increase the susceptibility to and/or incidence of breast cancer as well as other cancers that do not express cannabinoid receptors and are resistant to Delta9-THC-induced apoptosis.

Cannabidiol attenuates deficits of visuospatial associative memory induced by Δ9tetrahydrocannabinol

PubMed Central

Wright, M Jerry; Vandewater, Sophia A; Taffe, Michael A

2013-01-01

BACKGROUND AND PURPOSE Recent human studies suggest that recreational cannabis strains that are relatively high in cannabidiol (CBD) content produce less cognitive impairment than do strains with negligible CBD and similar Δ9tetrahydrocannabinol (THC) content. Self-selection in such studies means it is impossible to rule out additional variables which may determine both cannabis strain selection and basal cognitive performance level. Controlled laboratory studies can better determine a direct relationship. EXPERIMENTAL APPROACH In this study, adult male rhesus monkeys were assessed on visuospatial Paired Associates Learning and Self-Ordered Spatial Search memory tasks, as well as additional tests of motivation and manual dexterity. Subjects were challenged with THC (0.2, 0.5 mg·kg−1, i.m.) in randomized order and evaluated in the presence or absence of 0.5 mg·kg−1 CBD. KEY RESULTS CBD attenuated the effects of THC on paired associates learning and a bimanual motor task without affecting the detrimental effects of THC on a Self-Ordered Spatial Search task of working memory. CBD did not significantly reverse THC-induced impairment of a progressive ratio or a rotating turntable task. CONCLUSIONS AND IMPLICATIONS This study provides direct evidence that CBD can oppose the cognitive-impairing effects of THC and that it does so in a task-selective manner when administered simultaneously in a 1:1 ratio with THC. The addition of CBD to THC-containing therapeutic products may therefore help to ameliorate unwanted cognitive side-effects. LINKED ARTICLE This article is commented on by Mechoulam and Parker, pp 1363–1364 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12400 PMID:23550724

Real-time validation of the Dst Predictor model

USGS Publications Warehouse

McCollough, James P.; Young, Shawn L.; Rigler, E. Joshua; Simpson, Hal A.

2015-01-01

The Dst Predictor model, which has been running real-time in the Space Weather Analysis and Forecast System (SWAFS), provides 1-hour and 4-hour forecasts of the Dst index. This is useful for awareness of impending geomagnetic activity, as well as driving other real-time models that use Dst as an input. In this report, we examine the performance of this forecast model in detail. When validating indices it should be noted that performance is only with respect to a reference index as they are derived quantities assumed to reflect a state of the magnetosphere that cannot be directly measured. In this case U.S. Geological Survey (USGS) Definitive Dst is the reference index (Section 3). Whether or not the model better reflects the actual activity level is nearly impossible to discern and is outside the scope of this report. We evaluate the performance of the model by computing continuous predictant skill scores against USGS Definitive Dst values as “observations” (Section 4.2). The two sets of data are not well-correlated for both 1-hour and 4-hour forecasts. The Dst Predictor Prediction Efficiency for both the 1- and 4-hour forecasts suggests poor performance versus the climatological mean. However, the skill score against a nowcast persistence model is positive, suggesting value added by the Dst Predictor model. We further examine statistics for storm times (Section 4.3) with similar results: nowcast persistence performs worse than Dst Predictor.  Dst Predictor is superior to the nowcast persistence model for the metric used in this study. We recommend continued use of the DstPredictor model for 1-and4-hour Dst predictions along with active study of other Dst forecast models that do not rely on nowcast inputs (Section 6). The lack of certified requirements makes further recommendations difficult. A study of how the error in Dst translates to error in models and a better understanding of operational needs for magnetic storm warning are needed to determine such requirements. Nowcast persistence is often hard to beat for short term forecasts and specification and Dst Predictor clearly performs well against that standard (with 1-hour and 4-hour skill-scores of 0.233 and 0.485 respectively), although poor in absolute terms (with1-hourand4-hour prediction efficiencies of-64.6and-43.1, respectively).

Previous Exposure to Δ9-Tetrahydrocannibinol Enhances Locomotor Responding to but Not Self-Administration of AmphetamineS⃞

PubMed Central

Cortright, James J.; Lorrain, Daniel S.; Beeler, Jeff A.; Tang, Wei-Jen

2011-01-01

Previous exposure to amphetamine leads to enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced amphetamine self-administration. Here, we investigated the effects of exposure to Δ9-tetrahydrocannibinol (Δ9-THC) on behavioral and biochemical responding to amphetamine. Rats in different groups received five exposure injections of vehicle or one of five doses of Δ9-THC (0.4, 0.75, 1.5, 3.0, and 6.0 mg/kg i.p.) and were tested 2 days and 2 weeks later. Exposure to all but the lowest and highest doses of Δ9-THC enhanced the locomotor response to amphetamine (0.75 mg/kg i.p.), but all failed to enhance NAcc DA overflow in response to the drug. Moreover, exposure to 3.0 mg/kg i.p. Δ9-THC increased forskolin-evoked adenylyl cyclase activity in the NAcc and rats' locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg s.c.), suggesting that Δ9-THC sensitized locomotor responding to amphetamine by up-regulating postsynaptic DA receptor signaling in the NAcc. Finally, amphetamine self-administration (200 μg/kg/infusion i.v.) was enhanced in amphetamine (5 × 1.5 mg/kg i.p.)-exposed rats, but not in rats exposed to Δ9-THC (5 × 3.0 mg/kg i.p.). Previous exposure to this dose of Δ9-THC modestly increased apomorphine SA (0.5 mg/kg/infusion i.v.). Thus, unlike amphetamine exposure, exposure to Δ9-THC does not enhance the subsequent NAcc DA response to amphetamine or promote amphetamine self-administration. Although Δ9-THC leads to alterations in postsynaptic DA receptor signaling in the NAcc and these can affect the generation of locomotion, these neuroadaptations do not seem to be linked to the expression of enhanced amphetamine self-administration. PMID:21389094

Postmortem Fluid and Tissue Concentrations of THC, 11-OH-THC and THC-COOH.

PubMed

Saenz, Sunday R; Lewis, Russell J; Angier, Mike K; Wagner, Jarrad R

2017-07-01

Marijuana is the most commonly abused illicit drug worldwide. Marijuana is used for its euphoric and relaxing properties. However, marijuana use has been shown to result in impaired memory, cognitive skills and psychomotor function. The Federal Aviation Administration's Civil Aerospace Medical Institute conducts toxicological analysis on aviation fatalities. Due to severe trauma associated with aviation accidents, blood is not always available; therefore, the laboratory must rely on specimens other than blood for toxicological analysis in ~30-40% of cases. However, the postmortem distribution of cannabinoids has not been well characterized. The purpose of this research is to evaluate the distribution of Δ9-tetrahydrocannabinol (THC), and its metabolites, 11-hydroxy-tetrahydrocannabinol (11-OH-THC) and THC-COOH, in postmortem fluid and tissue specimens from 11 fatal aviation accident cases (2014-2015) previously found positive for cannabinoids. Specimens evaluated, when available, included: blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, brain, heart and bile. We developed and validated (following SWGTOX guidelines) a sensitive and robust method using solid-phase extraction and liquid chromatography-tandem mass spectrometry to identify and quantify THC, 11-OH-THC and THC-COOH in postmortem fluids and tissues. The method readily identified and quantified these cannabinoids in postmortem fluids and tissues below 1 ng/mL. Qualitative cannabinoid results within each case were comparable between blood and non-blood specimens. However, there was no consistent distribution of the cannabinoids between blood and any other fluids or tissues. Therefore, while quantitative interpretation of non-blood postmortem fluid and tissues samples is not prudent, a majority of the non-blood specimens tested could be suitable alternative/supplemental choices for qualitative cannabinoid detection. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

MOTOR VEHICLE CRASH FATALATIES AND UNDERCOMPENSATED CARE ASSOCIATED WITH LEGALIZATION OF MARIJUANA.

PubMed

Steinemann, Susan; Galanis, Daniel; Nguyen, Tiffany; Biffl, Walter

2018-05-21

Half of U.S. states have legalized medical cannabis (marijuana), some allow recreational use. The economic and public health effects of these policies are still being evaluated. We hypothesized that cannabis legalization was associated with an increase in the proportion of motor vehicle crash fatalities involving cannabis-positive drivers, and that cannabis use is associated with high-risk behavior and poor insurance status. Hawaii legalized cannabis in 2000. Fatality Analysis Reporting System (FARS) data were analyzed before (1993-2000) and after (2001-2015) legalization. Presence of cannabis (THC), methamphetamine, and alcohol in fatally injured drivers were compared. Data from the state's highest level trauma center were reviewed for THC status from 1997-2013. State Trauma Registry data from 2011-2015 were reviewed to evaluate association between cannabis, helmet/seatbelt use, and payor mix. THC-positivity among driver fatalities increased since legalization, with a three-fold increase from 1993-2000 to 2001-2015. Methamphetamine, which has remained illegal, and alcohol positivity were not significantly different before versus after 2000. THC-positive fatalities were younger, and more likely single-vehicle accidents, nighttime crashes, and speeding. They were less likely to have used a seatbelt or helmet. THC-positivity among all injured patients tested at our highest level trauma center increased from 11% before to 20% after legalization. From 2011-2015, THC-positive patients were significantly less likely to wear a seatbelt or helmet (33% vs 56%). They were twice as likely to have Medicaid insurance (28% vs 14%). Since legalization of cannabis, THC-positivity among MVC fatalities has tripled statewide, and THC-positivity among patients presenting to the highest level trauma center has doubled. THC-positive patients are less likely to use protective devices and more likely to rely on publically funded medical insurance. These findings have implications nationally and underscore the need for further research and policy development to address the public health effects and the costs of cannabis-related trauma. 3, original research, prognostic.

A Study on the Optimal Duration of Daylight Saving Time (DST) in Korea

NASA Astrophysics Data System (ADS)

Mihn, Byeong-Hee; Ahn, Young Sook; Kim, Dong-Bin; Yang, Hong-Jin

2009-09-01

Daylight saving time aims at spending effective daylight in summer season. Korea had enforced daylight saving time twelve times from 1948 to 1988. Since 1988, it is not executed, but it is recently discussed the resumption of DST. In this paper, we investigate the trend of DST in other countries, review the history of DST in Korea, and suggest the optimal DST duration in terms of astronomical aspects (times of sunrise and sunset). We find that the starting day of DST in Korea is apt for the second Sunday in May or the second Sunday in April according to the time of sunrise or to the difference between Korean standard meridian and observer's, respectively. We also discuss time friction that might be caused by time difference between DST and Korea Standard Time (KST).

Metacognitive evaluation in the avoidance of demand.

PubMed

Dunn, Timothy L; Lutes, David J C; Risko, Evan F

2016-09-01

In the current set of experiments our goal was to test the hypothesis that individuals avoid courses of action based on a kind of metacognitive evaluation of demand in a Demand Selection Task (DST). Individuals in Experiment 1 completed a DST utilizing visual stimuli known to yield a dissociation between performance and perceived demand. Patterns of demand avoidance followed that of perceived demand. Experiment 2 provided a replication of the aforementioned results, in addition to demonstrating a second dissociation between a peripheral physiological measure of demand (i.e., blink rates) and demand avoidance. Experiment 3 directly tested the assumption that individuals make use of a general metacognitive evaluation of task demand during selections. A DST was utilized in a forced-choice paradigm that required individuals to either select the most effortful, time demanding, or least accurate of 2 choices. Patterns of selections were similar across all rating dimensions, lending credit to this notion. Findings are discussed within a metacognitive framework of demand avoidance and contrasted to current theories. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients.

PubMed

Hong, M-S; Kim, Y; Cho, E-J; Lee, J-S; Kwak, H-K; Kim, J-H; Kim, C-T; Cho, J-S; Park, S-K; Jeon, D; Choi, Y-I; Lee, H; Eum, S-Y

2017-11-01

Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB. The isolates isolated from the sputum and different lung lesions of each patient were tested for phenotypic DST and genotyped using restriction fragment length polymorphism (RFLP) typing method. Genetic analysis to resistance to first and second line drugs was also performed. Five of nine patients were MDR-TB and three XDR-TB. DST results for ten anti-TB drugs were in accordance among different lung lesions in eight patients. However, only three of these eight patients showed the concordance of DST with sputum. Even though the isolates were heteroresistant, genotyping them by RFLP showed the clonal population in each individual patient. Six of eight followed-up patients achieved successful cure. In conclusion, the heteroresistance between sputum and lung lesions and a clonal population without mixed infection might provide useful information in establishing treatment regimen and surgery decision for MDR- and XDR-TB.

Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia.

PubMed

Ryan, Duncan; Drysdale, Alison J; Pertwee, Roger G; Platt, Bettina

2006-11-20

We have shown previously that the plant cannabinoid cannabidiol (CBD) elevates intracellular calcium levels in both cultured hippocampal neurones and glia. Here, we investigated whether the main psychotropic constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC) alone or in combination with other cannabis constituents can cause similar responses, and whether THC affects the responses induced by CBD. Our experiments were performed with 1 microM pure THC (pTHC), with 1 microM pure CBD (pCBD), with a high-THC, low CBD cannabis extract (eTHC), with a high-CBD, low THC cannabis extract (eCBD), with a mixture of eTHC and eCBD (THC:CBD=1:1) or with corresponding 'mock extracts' that contained only pTHC and pCBD mixed in the same proportion as in eTHC, eCBD or the 1:1 mixture of eTHC and eCBD. We detected significant differences in neurones both between the effects of pTHC and eTHC and between the effects of pCBD and eCBD. There were also differences between the Ca(2+) responses evoked in both neurones and glia by eTHC and mock eTHC, but not between eCBD and mock eCBD. A particularly striking observation was the much increased response size and maximal responder rates induced by the mixture of eTHC and eCBD than by the corresponding 1:1 mixture of pTHC and pCBD. Our data suggest that THC shares the ability of CBD to elevate Ca(2+) levels in neurones and glia, that THC and CBD interact synergistically and that the cannabis extracts have other constituents yet to be identified that can significantly modulate the ability of THC and CBD to raise Ca(2+) levels.

Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats.

PubMed

Klein, Charlotte; Karanges, Emily; Spiro, Adena; Wong, Alexander; Spencer, Jarrah; Huynh, Thanh; Gunasekaran, Nathan; Karl, Tim; Long, Leonora E; Huang, Xu-Feng; Liu, Kelly; Arnold, Jonathon C; McGregor, Iain S

2011-11-01

The interactions between Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) during chronic treatment, and at equivalent doses, are not well characterised in animal models. The aim of this study is to examine whether the behavioural effects of THC, and blood and brain THC levels are affected by pre-treatment with equivalent CBD doses. Adolescent rats were treated with ascending daily THC doses over 21 days (1 then 3 then 10 mg/kg). Some rats were given equivalent CBD doses 20 min prior to each THC injection to allow examination of possible antagonistic effects of CBD. During dosing, rats were assessed for THC and CBD/THC effects on anxiety-like behaviour, social interaction and place conditioning. At the end of dosing, blood and brain levels of THC, and CB(1) and 5-HT(1A) receptor binding were assessed. CBD potentiated an inhibition of body weight gain caused by chronic THC, and mildly augmented the anxiogenic effects, locomotor suppressant effects and decreased social interaction seen with THC. A trend towards place preference was observed in adolescent rats given CBD/THC but not those given THC alone. With both acute and chronic administration, CBD pre-treatment potentiated blood and brain THC levels, and lowered levels of THC metabolites (THC-COOH and 11-OH-THC). CBD co-administration did not alter the THC-induced decreases in CB(1) receptor binding and no drug effects on 5-HT(1A) receptor binding were observed. CBD can potentiate the psychoactive and physiological effects of THC in rats, most likely by delaying the metabolism and elimination of THC through an action on the CYP450 enzymes that metabolise both drugs.

A Dempster-Shafer Method for Multi-Sensor Fusion

DTIC Science & Technology

2012-03-01

position results for DST Mean Mod (or DST Mean for Case 1) to follow the same general path as the true aircraft . Also, if the points diverged from the true...of the aircraft . Its results were similar to those for DST True and Kalman. Also DST Mean had the same clustering of points as the others specifically...DST Mean values increasingly diverged as time t increased. Then Run 27 was very similar to Case 2 Run 5. Instead of following the true aircraft path

Provisional hourly values of equatorial Dst for 1971

NASA Technical Reports Server (NTRS)

Sugiura, M.; Poros, D. J.

1972-01-01

Tables and plots of provisional hourly values of the equatorial Dst index for 1971 are given, a table of daily mean Dst values for 1971 is also provided. The base line values for the four observatories, Hermanus, Kakioka, Honolulu, and San Juan, were obtained from extrapolations using the coefficients for the secular variations determined for the previous years. Examining the Dst values for quiet days, the base lines so determined appear to be slightly low, so that the Dst index for quiet periods tends to be high.

Sex differences in antinociceptive response to Δ-9-tetrahydrocannabinol and CP 55,940 in the mouse formalin test.

PubMed

LaFleur, Rebecca A; Wilson, Ronald P; Morgan, Daniel J; Henderson-Redmond, Angela N

2018-04-11

Cannabinoids have shown promise for the treatment of intractable pain states and may represent an alternative pharmacotherapy for pain management. A growing body of clinical evidence suggests a role for sex in pain perception and in cannabinoid response. We examined cannabinoid sensitivity and tolerance in male and female mice expressing a desensitization-resistant form (S426A/S430A) of the cannabinoid type 1 receptor (CB1R). Mice were assessed for acute and inflammatory nociceptive behaviors in the formalin test following pretreatment with either vehicle or mixed CB1R/CB2R agonists, Δ-9-tetrahydrocannabinol ([INCREMENT]-THC) (1-6 mg/kg) or CP 55,940 (0.06-0.2 mg/kg). Tolerance to the effects of 6 mg/kg [INCREMENT]-THC or 0.1 mg/kg CP 55,940 was examined by the formalin test following chronic daily dosing. Female mice showed decreased sensitivity to the effects of [INCREMENT]-THC and CP 55,940 compared with male mice. The S426A/S430A mutation increased the attenuation of nociceptive behaviors for both agonists in both sexes. Female mice displayed delayed tolerance to [INCREMENT]-THC compared with male mice, whereas the S426A/S430A mutation conferred a delay in tolerance to [INCREMENT]-THC in both sexes. Male S426A/S430A mutant mice also display resistance to tolerance to CP 55,940 compared with wild-type controls. This study demonstrates sex and genotype differences in response for two different cannabinoid agonists. The results underscore the importance of including both male and female mice in preclinical studies of pain and cannabinoid pharmacology.

Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans

PubMed Central

Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R.; Liberzon, Israel; Phan, K. Luan

2013-01-01

Pre-extinction administration of ∆9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 hours after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. PMID:24055595

Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats.

PubMed

Morley, Kirsten C; Li, Kong M; Hunt, Glenn E; Mallet, Paul E; McGregor, Iain S

2004-06-01

Cannabinoid-MDMA interactions were examined in male Wistar rats. MDMA (4 x 5 mg/kg or 2 x 10 mg/kg over 4 h on each of 2 days) was administered with or without Delta 9-tetrahydrocannabinol (THC) (4 x 2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2 x 0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2 x 5 mg/kg). Co-administered Delta 9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered Delta 9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered Delta 9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered Delta 9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors.

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.

Possible existence of convective currents in surfactant bulk solution in experimental pendant-bubble dynamic surface tension measurements.

PubMed

Moorkanikkara, Srinivas Nageswaran; Blankschtein, Daniel

2009-02-03

Traditionally, surfactant bulk solutions in which dynamic surface tension (DST) measurements are conducted using the pendant-bubble apparatus are assumed to be quiescent. Consequently, the transport of surfactant molecules in the bulk solution is often modeled as being purely diffusive when analyzing the experimental pendant-bubble DST data. In this Article, we analyze the experimental pendant-bubble DST data of the alkyl poly (ethylene oxide) nonionic surfactants, C12E4 and C12E6, and demonstrate that both surfactants exhibit "superdiffusive" adsorption kinetics behavior with characteristics that challenge the traditional assumption of a quiescent surfactant bulk solution. In other words, the observed superdiffusive adsorption behavior points to the possible existence of convection currents in the surfactant bulk solution. The analysis presented here involves the following steps: (1) constructing an adsorption kinetics model that corresponds to the fastest rate at which surfactant molecules adsorb onto the actual pendant-bubble surface from a quiescent solution, (2) predicting the DST behaviors of C12E4 and C12E6 at several surfactant bulk solution concentrations using the model constructed in step 1, and (3) comparing the predicted DST profiles with the experimental DST profiles. This comparison reveals systematic deviations for both C12E4 and C12E6 with the following characteristics: (a) the experimental DST profiles exhibit adsorption kinetics behavior, which is faster than the predicted fastest rate of surfactant adsorption from a quiescent surfactant bulk solution at time scales greater than 100 s, and (b) the experimental DST profiles and the predicted DST behaviors approach the same equilibrium surface tension values. Characteristic (b) indicates that the cause of the observed systematic deviations may be associated with the adsorption kinetics mechanism adopted in the model used rather than with the equilibrium behavior. Characteristic (a) indicates that the actual surfactant bulk solution in which the DST measurement was conducted, most likely, cannot be considered to be quiescent at time scales greater than 100 s. Accordingly, the observed superdiffusive adsorption behavior is interpreted as resulting from convection currents present in a nonquiescent surfactant bulk solution. Convection currents accelerate the surfactant adsorption process by increasing the rate of surfactant transport in the bulk solution. The systematic nature of the deviations observed between the predicted DST profiles and the experimental DST behavior for C12E4 and C12E6 suggests that the nonquiescent nature of the surfactant bulk solution may be intrinsic to the experimental pendant-bubble DST measurement approach. To validate this possibility, we identified generic features in the experimental DST data when DST measurements are conducted in a nonquiescent surfactant bulk solution, and the DST measurements are analyzed assuming that the surfactant bulk solution is quiescent. An examination of the DST literature reveals that these identified generic features are quite general and are observed in the experimental DST data of several other surfactants (decanol, nonanol, C10E8, C14E8, C12E8, and C10E4) measured using the pendant-bubble apparatus.

Development of a Δ9-Tetrahydrocannabinol Amino Acid-Dicarboxylate Prodrug With Improved Ocular Bioavailability

PubMed Central

Adelli, Goutham R.; Bhagav, Prakash; Taskar, Pranjal; Hingorani, Tushar; Pettaway, Sara; Gul, Waseem; ElSohly, Mahmoud A.; Repka, Michael A.; Majumdar, Soumyajit

2017-01-01

Purpose The aim of the present study was to evaluate the utility of the relatively hydrophilic Δ9-tetrahydrocannabinol (THC) prodrugs, mono and di-valine esters (THC-Val and THC-Val-Val) and the amino acid (valine)-dicarboxylic acid (hemisuccinate) ester (THC-Val-HS), with respect to ocular penetration and intraocular pressure (IOP) lowering activity. THC, timolol, and pilocarpine eye drops were used as controls. Methods THC-Val, THC-Val-Val, and THC-Val-HS were synthesized and chemically characterized. Aqueous solubility and in vitro transcorneal permeability of THC and the prodrugs, in the presence of various surfactants and cyclodextrins, were determined. Two formulations were evaluated for therapeutic activity in the α-chymotrypsin induced rabbit glaucoma model, and the results were compared against controls comprising of THC emulsion and marketed timolol maleate and pilocarpine eye drops. Results THC-Val-HS demonstrated markedly improved solubility (96-fold) and in vitro permeability compared to THC. Selected formulations containing THC-Val-HS effectively delivered THC to the anterior segment ocular tissues in the anesthetized rabbits: 62.1 ng/100 μL of aqueous humor (AH) and 51.4 ng/50 mg of iris ciliary bodies (IC) (total THC). The duration and extent of IOP lowering induced by THC-Val-HS was 1 hour longer and 10% greater, respectively, than that obtained with THC and was comparable with the pilocarpine eye drops. Timolol ophthalmic drops, however, exhibited a longer duration of activity. Both THC and THC-Val-HS were detected in the ocular tissues following multiple dosing of THC-Val-HS in conscious animals. The concentration of THC in the iris-ciliary bodies at the 60- and 120-minute time points (53 and 57.4 ng/50 mg) were significantly greater than that of THC-Val-HS (24.2 and 11.3 ng/50 mg). Moreover, at the two time points studied, the concentration of THC was observed to increase or stay relatively constant, whereas THC-Val-HS concentration decreased by at least 50%. A similar trend was observed in the retina-choroid tissues. Conclusions A combination of prodrug derivatization and formulation development approaches significantly improved the penetration of THC into the anterior segment of the eye following topical application. Enhanced ocular penetration resulted in significantly improved IOP-lowering activity. PMID:28399267

Smoke on the water-Oral fluid analysis at sea.

PubMed

Griffiths, Andrew; Leonars, Richard; Hadley, Lenore; Stephenson, Mark; Teale, Richard

2017-09-01

This study outlines the operational challenges and findings of an illicit drug oral fluid testing program carried out on the skippers (those in charge) of water vessels in Queensland, Australia. Between 2010 and 2016, 953 tests of skippers were conducted on water (waterside) for three proscribed illicit drugs; delta-9-tetrahydrocannabinol (THC), methylamphetamine (MA) and 3,4-methylendioxymethylamphetamine (MDMA). 126 (13%) of the skippers tested returned an on-site positive during waterside testing, 125 were confirmed positive for one or more illicit drug by subsequent laboratory analysis, whilst one skipper did not provide an oral fluid sample for confirmatory analysis. The skippers were entirely male (100%) with an average age of 39 years (range 17-59). THC was by far the most common drug detected (91%); MA was detected in 22% of skippers and a combination or THC and MA in 14% of specimens. MDMA was identified only once during the study, this being in combination with THC. As a single waterside operation can take more than a week, operational pre-planning becomes essential. Aspects of the operation such as, weather, shift times, food, testing consumables, sleeping quarters, hygiene, liaison between different agencies and multiple other factors need to be taken into account prior to commencement. A waterside operation must be mobile and, in Queensland at least, able to cover a large area of water. There is also a much lower volume of vessels likely to be encountered at sea compared to a roadside operation targeting motor vehicles. Copyright © 2017 Elsevier B.V. All rights reserved.

Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

PubMed

Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

2015-09-01

The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Circulation and oxygen cycling in the Mediterranean Sea: Sensitivity to future climate change

NASA Astrophysics Data System (ADS)

Powley, Helen R.; Krom, Michael D.; Van Cappellen, Philippe

2016-11-01

Climate change is expected to increase temperatures and decrease precipitation in the Mediterranean Sea (MS) basin, causing substantial changes in the thermohaline circulation (THC) of both the Western Mediterranean Sea (WMS) and Eastern Mediterranean Sea (EMS). The exact nature of future circulation changes remains highly uncertain, however, with forecasts varying from a weakening to a strengthening of the THC. Here we assess the sensitivity of dissolved oxygen (O2) distributions in the WMS and EMS to THC changes using a mass balance model, which represents the exchanges of O2 between surface, intermediate, and deep water reservoirs, and through the Straits of Sicily and Gibraltar. Perturbations spanning the ranges in O2 solubility, aerobic respiration kinetics, and THC changes projected for the year 2100 are imposed to the O2 model. In all scenarios tested, the entire MS remains fully oxygenated after 100 years; depending on the THC regime, average deep water O2 concentrations fall in the ranges 151-205 and 160-219 µM in the WMS and EMS, respectively. On longer timescales (>1000 years), the scenario with the largest (>74%) decline in deep water formation rate leads to deep water hypoxia in the EMS but, even then, the WMS deep water remains oxygenated. In addition, a weakening of THC may result in a negative feedback on O2 consumption as supply of labile dissolved organic carbon to deep water decreases. Thus, it appears unlikely that climate-driven changes in THC will cause severe O2 depletion of the deep water masses of the MS in the foreseeable future.

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil.

PubMed

Ramalho, D M P; Miranda, P F C; Andrade, M K; Brígido, T; Dalcolmo, M P; Mesquita, E; Dias, C F; Gambirasio, A N; Ueleres Braga, J; Detjen, A; Phillips, P P J; Langley, I; Fujiwara, P I; Squire, S B; Oliveira, M M; Kritski, A L

2017-08-15

The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

High pre-diagnosis attrition among patients with presumptive MDR-TB: an operational research from Bhopal district, India.

PubMed

Shewade, Hemant Deepak; Kokane, Arun M; Singh, Akash Ranjan; Verma, Manoj; Parmar, Malik; Chauhan, Ashish; Chahar, Sanjay Singh; Tiwari, Manoj; Khan, Sheeba Naz; Gupta, Vivek; Tripathy, Jaya Prasad; Nagar, Mukesh; Singh, Sanjai Kumar; Mehra, Pradeep Kumar; Kumar, Ajay Mv

2017-04-04

Pre-diagnosis attrition needs to be addressed urgently if we are to make progress in improving MDR-TB case detection and achieve universal access to MDR-TB care. We report the pre-diagnosis attrition, along with factors associated, and turnaround times related to the diagnostic pathway among patient with presumptive MDR-TB in Bhopal district, central India (2014). Study was conducted under the Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all registered TB cases in Bhopal district that met the presumptive MDR-TB criteria (eligible for DST) in 2014. In quarter 1, Line Probe Assay (LPA) was used if sample was smear/culture positive. Quarter 2 onwards, LPA and Cartridge-based Nucleic Acid Amplification Test (CbNAAT) was used for smear positive and smear negative samples respectively. Pre-diagnosis attrition was defined as failure to undergo DST among patients with presumptive MDR-TB (as defined by the programme). Of 770 patients eligible for DST, 311 underwent DST and 20 patients were diagnosed as having MDR-TB. Pre-diagnosis attrition was 60% (459/770). Among those with pre-diagnosis attrition, 91% (417/459) were not identified as 'presumptive MDR-TB' by the programme. TAT [median (IQR)] to undergo DST after eligibility was 4 (0, 10) days. Attrition was more than 40% across all subgroups. Age more than 64 years; those from a medical college; those eligible in quarter 1; patients with presumptive criteria 'previously treated - recurrent TB', 'treatment after loss-to-follow-up' and 'previously treated-others'; and patients with extra-pulmonary TB were independent risk factors for not undergoing DST. High pre-diagnosis attrition was contributed by failure to identify and refer patients. Attrition reduced modestly with time and one factor that might have contributed to this was introduction of CbNAAT in quarter 2 of 2014. General health system strengthening which includes improvement in identification/referral and patient tracking with focus on those with higher risk for not undergoing DST is urgently required.

76 FR 32227 - DST Systems, Inc., Including On-Site Leased Workers From Comsys Information Technology Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

... Technologies, a wholly owned subsidiary of DSI Systems, Inc., Boston, Massachusetts operated in conjunction... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,649; TA-W-74,649a] DST Systems... Kelly Services Kansas City, MO; DST Technologies, a Wholly Owned Subsidiary of DST Systems, Inc., Boston...

HANFORD DOUBLE SHELL TANK (DST) THERMAL & SEISMIC PROJECT SEISMIC ANALYSIS IN SUPPORT OF INCREASED LIQUID LEVEL IN 241-AP TANK FARMS

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

MACKEY TC; ABBOTT FG; CARPENTER BG

2007-02-16

The overall scope of the project is to complete an up-to-date comprehensive analysis of record of the DST System at Hanford. The "Double-Shell Tank (DST) Integrity Project - DST Thermal and Seismic Project" is in support of Tri-Party Agreement Milestone M-48-14.

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.

delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

PubMed

Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

2011-10-01

Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC.

PubMed

Hložek, Tomáš; Uttl, Libor; Kadeřábek, Lukáš; Balíková, Marie; Lhotková, Eva; Horsley, Rachel R; Nováková, Pavlína; Šíchová, Klára; Štefková, Kristýna; Tylš, Filip; Kuchař, Martin; Páleníček, Tomáš

2017-12-01

Metabolic and behavioural effects of, and interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are influenced by dose and administration route. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous (sc.) THC, CBD and THC+CBD. Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD in serum and brain were determined over 24h, locomotor activity (open field) and sensorimotor gating (prepulse inhibition, PPI) were also evaluated. In line with recent knowledge we expected metabolic and behavioural interactions between THC and CBD. While cannabinoid serum and brain levels rapidly peaked and diminished after pulmonary administration, sc. and oral administration produced long-lasting levels of cannabinoids with oral reaching the highest brain levels. Except pulmonary administration, CBD inhibited THC metabolism resulting in higher serum/brain levels of THC. Importantly, following sc. and oral CBD alone treatments, THC was also detected in serum and brain. S.c. cannabinoids caused hypolocomotion, oral treatments containing THC almost complete immobility. In contrast, oral CBD produced mild hyperlocomotion. CBD disrupted, and THC tended to disrupt PPI, however their combination did not. In conclusion, oral administration yielded the most pronounced behavioural effects which corresponded to the highest brain levels of cannabinoids. Even though CBD potently inhibited THC metabolism after oral and sc. administration, unexpectedly it had minimal impact on THC-induced behaviour. Of central importance was the novel finding that THC can be detected in serum and brain after administration of CBD alone which, if confirmed in humans and given the increasing medical use of CBD-only products, might have important legal and forensic ramifications. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

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 the doses chosen in this study. Significantly higher AUC and Cmax and shorter tmax were found for females as compared with males.

Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing's syndrome.

PubMed

Giordano, Roberta; Berardelli, Rita; Karamouzis, Ioannis; D'Angelo, Valentina; Picu, Andreea; Zichi, Clizia; Fussotto, Beatrice; Manzo, Maria; Mengozzi, Giulio; Ghigo, Ezio; Arvat, Emanuela

2013-09-01

The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing's syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing's syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels < 3 and < 1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.

Executive Function Skills of 6 to 8 Year Olds: Brain and Behavioral Evidence and Implications for School Achievement

PubMed Central

Molfese, Victoria J.; Molfese, Peter J.; Molfese, Dennis L.; Rudasill, Kathleen M.; Armstrong, Natalie; Starkey, Gillian

2010-01-01

Academic and social success in school has been linked to children’s self-regulation. This study investigated the assessment of the executive function (EF) component of self-regulation using a low-cost, easily administered measure to determine whether scores obtained from the behavioral task would agree with those obtained using a laboratory-based neuropsychological measure of EF skills. The sample included 74 children (37 females; M = 86.2 months) who participated in two assessments of working memory and inhibitory control: Knock-Tap (NEPSY: Korkman, Kirk, and Kemp, 1998), and participation in event-related potential (ERP) testing that included the Directional Stroop Test (Davidson, Cruess, Diamond, O’Craven, & Savoy, 1999). Three main findings emerged. First, children grouped as high versus low performing on the NEPSY Knock-Tap Task were found to performed differently on the more difficult conditions of the DST (the Incongruent and Mixed Conditions), suggesting that the Knock-Tap Task as a low-cost and easy to administer assessment of EF skills may be one way for teachers to identify students with poor inhibitory control skills. Second, children’s performance on the DST was strongly related to their ERP responses, adding to evidence that differences in behavioral performance on the DST as a measure of EF skills reflect corresponding differences in brain processing. Finally, differences in brain processing on the DST task also were found when the children were grouped based on Knock-Tap performance. Simple screening procedures can enable teachers to identify children whose distractibility, inattentiveness, or poor attention spans may interfere with classroom learning. PMID:20798857

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.

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.

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.

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.

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.

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.

Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption.

PubMed

Stern, Cristina A J; Gazarini, Lucas; Vanvossen, Ana C; Zuardi, Antonio W; Galve-Roperh, Ismael; Guimaraes, Francisco S; Takahashi, Reinaldo N; Bertoglio, Leandro J

2015-06-01

Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level. We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation. Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples. Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation. Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Architectural constructs of Ampex DST

NASA Technical Reports Server (NTRS)

Johnson, Clay

1993-01-01

The DST 800 automated library is a high performance, automated tape storage system, developed by AMPEX, providing mass storage to host systems. Physical Volume Manager (PVM) is a volume server which supports either a DST 800, DST 600 stand alone tape drive, or a combination of DST 800 and DST 600 subsystems. The objective of the PVM is to provide the foundation support to allow automated and operator assisted access to the DST cartridges with continuous operation. A second objective is to create a data base about the media, its location, and its usage so that the quality and utilization of the media on which specific data is recorded and the performance of the storage system may be managed. The DST tape drive architecture and media provides several unique functions that enhance the ability to achieve high media space utilization and fast access. Access times are enhanced through the implementation of multiple areas (called system zones) on the media where the media may be unloaded. This reduces positioning time in loading and unloading the cartridge. Access times are also reduced through high speed positioning in excess of 800 megabytes per second. A DST cartridge can be partitioned into fixed size units which can be reclaimed for rewriting without invalidating other recorded data on the tape cartridge. Most tape management systems achieve space reclamation by deleting an entire tape volume, then allowing users to request a 'scratch tape' or 'nonspecific' volume when they wish to record data to tape. Physical cartridge sizes of 25, 75, or 165 gigabytes will make this existing process inefficient or unusable. The DST cartridge partitioning capability provides an efficient mechanism for addressing the tape space utilization problem.

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.

U.S. Geological Survey Near Real-Time Dst Index

USGS Publications Warehouse

Gannon, J.L.; Love, J.J.; Friberg, P.A.; Stewart, D.C.; Lisowski, S.W.

2011-01-01

The operational version of the United States Geological Survey one-minute Dst index (a global geomagnetic disturbance-intensity index for scientific studies and definition of space-weather effects) uses either four- or three-station input (including Honolulu, Hawaii; San Juan, Puerto Rico; Hermanus, South Africa; and Kakioka, Japan; or Honolulu, San Juan and Guam) and a method based on the U.S. Geological Survey definitive Dst index, in which Dst is more rigorously calculated. The method uses a combination of time-domain techniques and frequency-space filtering to produce the disturbance time series at an individual observatory. The operational output is compared to the U.S. Geological Survey one-minute Dst index (definitive version) and to the Kyoto (Japan) Final Dst to show that the U.S. Geological Survey operational output matches both definitive indices well.

Does the transition into daylight saving time really cause partial sleep deprivation?

PubMed

Toth Quintilham, Manoel Carlos; Adamowicz, Taísa; Pereira, Erico Felden; Pedrazzoli, Mario; Louzada, Fernando Mazzilli

2014-01-01

To identify possible changes in the sleep patterns according to chronotype in undergraduate students during the daylight saving time (DST) transition. A total of 378 students answered the Morningness-Eveningness Questionnaire (MEQ) to determine their chronotype and kept a diary about sleep-wake schedules 1 week before and after the DST transition. Oral mucosal cell samples were collected for genetic analysis. After the DST transition, intermediate types (I-types) delayed bedtime and increased their time in bed and all groups delayed their wake-up time. All groups presented a shorter phase angle between sunset and the bedtime after the DST transition. On the other hand, only E-types showed a tendency to reduce the phase angle between sunrise and wake-up time, while I-types and M-types kept the same phase angles between sunrise and wake-up time after the DST transition. The polymorphisms in the human genes CLOCK and PER3 were not associated with individual differences in sleep patterns, nor were they associated with an adjustment to the DST transition. Under the new set of social times determined by DST, the adjustment was only partial. I-types delayed bedtime and all groups delayed their wake-up times after the beginning of DST. Consequently, the time in bed after the DST transition was not reduced; Morning (M-types) and Evening-types (E-types) kept the same time in bed and I-types showed an increase on it.

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'.

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

PubMed

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

2012-06-01

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

Clofazimine drug susceptibility testing for Mycobacterium tuberculosis: the case of using the right diluent.

PubMed

Sng, Li-Hwei; Peh, Justine Woei Ling; Lee Kee, Melody Tai; Ya'akob, Nurhazirah Bte Mohd; Ong, Rick Twee-Hee; Wong, Christopher W; Chee, Cynthia Bin Eng; Wang, Yee Tang

2018-06-08

Accurate and reliable drug susceptibility testing (DST) is essential for the effective treatment and control of tuberculosis. With the increase in drug-resistant organisms, newer and less conventional antimicrobial agents are used for treatment. Recently, we found an unprecedented rise in the number of clofazimine-resistant Mycobacterium tuberculosis isolates in our laboratory. An investigation found that this phenomenon was due to a change in the method of drug preparation. We performed studies to assess the impact of water and dimethyl sulfoxide (DMSO) as a final diluent for clofazimine drug testing. Based on our findings, the use of DMSO as a solvent for M. tuberculosis DST was optimised using the BACTEC MGIT 960 platform. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells

PubMed Central

Sido, Jessica M.; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

2015-01-01

Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression. Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts. To this end, we studied HvGD by injecting H-2k splenocytes into H-2b mice and analyzing the immune response in the draining ingLNs. THC treatment significantly reduced T cell proliferation and activation in draining LNs of the recipient mice and decreased early stage rejection-indicator cytokines, including IL-2 and IFN-γ. THC treatment also increased the allogeneic skin graft survival. THC treatment in HvGD mice led to induction of MDSCs. Using MDSC depletion studies as well as adoptive transfer experiments, we found that THC-induced MDSCs were necessary for attenuation of HvGD. Additionally, using pharmacological inhibitors of CB1 and CB2 receptors and CB1 and CB2 knockout mice, we found that THC was working preferentially through CB1. Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection. PMID:26034207

Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: 18F-Fallypride Positron Emission Tomography Study

PubMed Central

Kuepper, Rebecca; Ceccarini, Jenny; Lataster, Johan; van Os, Jim; van Kroonenburgh, Marinus; van Gerven, Joop M. A.; Marcelis, Machteld; Van Laere, Koen; Henquet, Cécile

2013-01-01

Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and 18F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ9-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ9-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in 18F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ9-THC administration, reflecting dopamine release. While Δ9-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ9-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ9-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis. PMID:23936196

Delta-9-tetrahydrocannabinol (THC) history fails to affect THC's ability to induce place preferences in rats.

PubMed

Hempel, Briana J; Wakeford, Alison G P; Clasen, Matthew M; Friar, Mary A; Riley, Anthony L

2016-05-01

In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats. The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg). THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC. The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties. Copyright © 2016 Elsevier Inc. All rights reserved.

Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract.

PubMed

Nadulski, Thomas; Sporkert, Frank; Schnelle, Martin; Stadelmann, Andreas M; Roser, Patrik; Schefter, Tom; Pragst, Fritz

2005-01-01

Besides the psychoactive Delta(9)-tetrahydrocannabinol (THC), hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol (CBD) and of the degradation product cannabinol (CBN). The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. Therefore, a method for the simultaneous quantitative determination of THC, its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), CBD and CBN from plasma was developed. The method was based on automatic solid-phase extraction with C(18) ec columns, derivatization with N,O-bistrimethylsilyltrifluoroacetamide (BSTFA), and gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) with deuterated standards. The limits of detection were between 0.15 and 0.29 ng/mL for THC, 11-OH-THC, THC-COOH, and CBD and 1.1 ng/mL for CBN. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract. The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL (mean 4.05 ng/mL) for THC, 1.8 and 12.3 ng/mL (mean 4.9 ng/mL) for 11-OH-THC, 19 and 71 ng/mL (mean 35 ng/mL) for THC-COOH, and 0.2 and 2.6 ng/mL (mean 0.95 ng/mg) for CBD. The peak concentrations (mean values) of THC, 11-OH-THC, THC-COOH, and CBD were observed at 56, 82, 115, and 60 min, respectively, after intake. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. Therefore, the concentration ratio 11-OH-THC/THC was discussed as a criterion for distinguishing oral from inhalative cannabis consumption.

Validation of a Paper and Pencil Test Battery for the Diagnosis of Minimal Hepatic Encephalopathy in Korea.

PubMed

Jeong, Jae Yoon; Jun, Dae Won; Bai, Daiseg; Kim, Ji Yean; Sohn, Joo Hyun; Ahn, Sang Bong; Kim, Sang Gyune; Kim, Tae Yeob; Kim, Hyoung Su; Jeong, Soung Won; Cho, Yong Kyun; Song, Do Seon; Kim, Hee Yeon; Jung, Young Kul; Yoon, Eileen L

2017-09-01

The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955). © 2017 The Korean Academy of Medical Sciences.

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.

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

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

Biological markers of melancholia and reclassification of depressive disorders.

PubMed

Greden, J F

1982-01-01

Pathophysiological markers of melancholia are being developed in four major areas: 1) neuroendocrine; 2) sleep; 3) psychomotor and 4) biochemical. Neuroendocrine markers include a failure of suppress plasma cortisol secretion in the dexamethasone suppression test (DST), diminished thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH stimulation test), and blunted growth hormone response to a variety of stimulating agents such as d-amphetamine, methylamphetamine, clonidine, L-dopa and insulin (growth hormone test). Of these, the DST is the best standardized. It is a highly specific laboratory marker with documented value in diagnosis, assessing prognosis and monitoring treatment progress. Sleep EEG abnormalities include reduced REM latency, increased REM density, reduction in delta sleep and impaired sleep efficiency. Sleep EEGs are pragmatically difficult, but results are quite specific. Elongated speech pause time (SPT) during "automatic speech" is a promising marker of psychomotor regulation. This simple, non-invasive measure may have special value in reducing clinical subjectivity and in monitoring treatment progress. Biochemical markers include: 1) platelet monoamine oxidase (MAO) activity; 2) in vitro lithium RBC transport and 3) urinary MHPG levels. Standardizations of biochemical tests are still lacking. Most biological tests for melancholia operate by indirectly "marking" CNS limbic system dysfunction. For wide acceptance, a test must be safe, moderately sensitive, highly specific, practical, relatively inexpensive and not significantly altered by common anti-depressant treatments. The DST best meets these criteria at this time. Proper utilization of test results requires knowledge of baseline prevalence rates and of the concepts of sensitivity (true-positive rate), specificity (true negative rate) and positive and negative predictive values (diagnostic confidence). No single marker will meet all clinical needs. Combinations or serial use of tests will hopefully enhance their already considerable usefulness.

Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging.

PubMed

Toyota, Yasunori; Miyake, Keisuke; Kawai, Nobuyuki; Hatakeyama, Tetsuhiro; Yamamoto, Yuka; Toyohara, Jun; Nishiyama, Yoshihiro; Tamiya, Takashi

2015-01-01

3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, (18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of (11)C-4DST PET in the diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET. Twenty patients with primary and recurrent brain gliomas underwent (18)F-FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were compared among different glioma grades. Correlation between the Ki-67 labeling index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also examined. (11)C-4DST uptake was significantly higher than that of (18)F-FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT. No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were noted among different glioma grades. Linear regression analysis showed a significant correlation between the Ki-67 labeling index and the T/N ratio of (11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of (11)C-4DST and (18)F-FLT in the tumor (r = 0.79, P = 0.0001). The present study demonstrates that (11)C-4DST is useful for the imaging of human brain gliomas with PET. A relatively higher background uptake of (11)C-4DST in the normal brain compared to (18)F-FLT limits the detection of low-tracer-uptake tumors. Moreover, no superiority was found in (11)C-4DST over (18)F-FLT in the evaluation of cell proliferation.

[Tetrahydrocannabinol pharmacokinetics; new synthetic cannabinoids; road safety and cannabis].

PubMed

Goullé, Jean-Perre; Guerbet, Michel

2014-03-01

Delta-9-tetrahydrocannabinol (THC) is the main psychoactive ingredient of cannabis, a drug which is commonly smoked This paper focuses on the pharmacokinetics of THC. The average THC content in cannabis plant material has risen by a factor offour over the past 20 years, from 4% to 16%. This increase has important implications not only for the pharmacokinetics but also for the pharmacology of THC The mean bioavailability of THC in smoked cannabis is about 25%. In a cigarette containing 3.55% of THC, a peak plasma level of about 160 ng/mL occurs approximately 10 min after inhalation. THC is quickly cleared from plasma in a multiphasic manner and is widely distributed to tissues, leading to its pharmacologic effects. Body fat is a long-term storage site. This particular pharmacokinetic behavior explains the lack of correlation between the THC blood level and clinical effects, contrary to ethanol. The main THC metabolites are 11-OH-THC (the only active metabolite) and THC-COOH, which is eliminated in feces and urine over several weeks. Therefore, abstinence can be established by analyzing THC-COOH in urine, while blood THC analysis is used to confirm recent exposure. Cannabis is the main illicit drug found among vehicle drivers. Various traffic safety studies indicate that recent use of this drug at least doubles the risk of causing an accident, and that simultaneous alcohol consumption multiplies this risk by afactor of 14. Since 2009, synthetic cannabinoids have emerged on the illicit drug market. These substances act on the same CB1 receptors as THC, but with higher afinity. Their pharmacokinetics differs from that of THC, as they are metabolized into multiple derivatives, most of which are more active than THC itself.

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

A tale of two theories: How the adiabatic response and ULF waves affect relativistic electrons

NASA Astrophysics Data System (ADS)

Green, J. C.; Kivelson, M. G.

2001-11-01

Using data from the Comprehensive Energetic Particle and Pitch Angle Distribution (CEPPAD)-High Sensitivity Telescope (HIST) instrument on the Polar spacecraft and ground magnetometer data from the 210 meridian magnetometer chain, we test the ULF wave drift resonance theory proposed to explain relativistic electron phase space density enhancements. We begin by investigating changes in electron flux due to the ``Dst effect.'' The Dst effect refers to the adiabatic response of relativistic electrons to changes in the magnetic field characterized by the Dst index. The Dst effect, assuming no loss or addition of new electrons, produces reversible order of magnitude changes in relativistic electrons flux measured at fixed energy, but it cannot account for the flux enhancement that occurs in the recovery phase of most storms. Liouville's theorem states that phase space density expressed in terms of constant adiabatic invariants is unaffected by adiabatic field changes and thus is insensitive to the Dst effect. It is therefore useful to express flux measurements in terms of phase space densities at constant first, second and third adiabatic invariants. The phase space density is determined from the CEPPAD-HIST electron detector that measures differential directional flux of electrons from 0.7 to 9 MeV and the Tsyganenko 96 field model. The analysis is done for January to June 1997. The ULF wave drift resonance theory that we test proposes that relativistic electrons are accelerated by an m=2 toroidal or poloidal mode wave whose frequency equals the drift frequency of the electron. The theory is tested by comparing the relativistic electron phase space densities to wave power determined at three ground stations with L* values of 4.0, 5.7 and 6.2. Comparison of the wave data to the phase space densities shows that five out of nine storm events are consistent with the ULF wave drift resonance mechanism, three out of nine give ambiguous support to the model, and one event has high ULF wave power at the drift frequency of the electrons but no corresponding phase space density enhancement suggesting that ULF wave power alone is not sufficient to cause an electron response. Two explanations of the anomalous event are investigated including excessive loss of electrons to the magnetopause and wave duration.

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.

Review of Urinalysis Drug Testing Program. Report by a Panel of Army and Civilian Experts in Toxicology and Drug Testing Legal Issues for the Surgeon General of the U.S. Army

DTIC Science & Technology

1983-12-12

the National Institute on Drug Abuse (NIDA). Dr. Simon is a consultant on forensic toxicology and currently is the Director of Industrial...THC ratio algorithm, and no laboratory has the personnel trained to provide forensic testimony on the THC or other drug GC/MS data. d. The GC/MS...adequate expertise to support GC/MS internally and forensically document (for courts-martial) GC/MS. The USAF Homestead AFB case is a glaring example of

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

The effects of Δ9-Tetrahydrocannabinole treatment on gonadal micro-vascularization and affected fertility examined by SEM and 3D-morphometry

NASA Astrophysics Data System (ADS)

Erlbacher, K. M. T.; Minnich, B.

2015-10-01

The present study focuses on the effects of Δ9-tetrahydrocannabinol (THC) on the reproductive system in nude rats with special emphasis on how Δ9-THC impacts the vascularization of testes which in turn indirectly influences fertility. Basically, Δ9-tetrahydrocannabinol (THC) causes not only negative (psychoactive) effects in the human body as cannabinole administration in medical use (dose-dependent) offers multiple new treatment opportunities such as pain relief or containment of various cancers. Concerning the reproductive system it strongly influences CB-receptors along the hypothalamic-pituitary-gonadal axis resulting in reduced plasma testosterone levels. There is also altered sperm quality parameters reported such as sperm motility or sperm count. On the other hand Δ9-THC effects endothelial growth factors (VEGF, Ang-1 etc.) respectively acts on their specific receptors which in turn modify angiogenesis and vascularization of tissues and organs (e.g. tumorous tissues). This leads to new therapeutical strategies in the suppression of various cancers by inhibiting (neo-)vascularization and in turn famishment of tumorous tissues (lack of nutrition supply). Here we studied the micro-vascularization of gonads in a long-term THC-treated nude rat model by vascular corrosion casting, SEM and 3D-morphometry.

40 CFR 86.143-96 - Calculations; evaporative emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

....1005(f): ER28AP14.005 Where: m THCE = the sum of the mass of THCE in the SHED. m THC = the mass of THC and all oxygenated hydrocarbons in the SHED, as measured by the FID. Calculate THC mass based on ρ THC. ρ THC = the effective C1-equivalent density of THC as specified in 40 CFR 1066.1005(f). m OHCi = the...

Diagnostic value of ACTH stimulation test in determining the subtypes of primary aldosteronism.

PubMed

Jiang, Yiran; Zhang, Cui; Wang, Weiqing; Su, Tingwei; Zhou, Weiwei; Jiang, Lei; Zhu, Wei; Xie, Jing; Ning, Guang

2015-05-01

Adrenal venous sampling is recommended as the golden standard for subtyping primary aldosteronism (PA). However, it is invasive and inconvenient, and seeking a better way to make differential diagnosis of PA is necessary. The objective of the study was to evaluate the diagnostic value of ACTH stimulation test under 1 mg dexamethasone suppression test (DST) in determining the subtypes of PA. Ninety-five patients with PA confirmed by saline infusion test were included in this study. According to adrenal venous sampling and histopathology, 39 patients were diagnosed as bilateral adrenal hyperplasia (BAH), 37 as aldosterone-producing adenoma (APA), and 19 as unilateral adrenal hyperplasia (UAH). An ACTH stimulation test under 1 mg DST was performed in all patients. Plasma aldosterone and cortisol levels were measured every 30 minutes until 120 minutes after the iv injection of 50 IU ACTH. During the ACTH stimulation test, aldosterone levels in APA and UAH were similar (P > .05) but higher than those in BAH (P < .001). Furthermore, stimulated aldosterone levels of unilateral PA (APA and UAH) were significantly higher than bilateral PA (BAH) (P < .001). Receiver-operated characteristics curve analyses showed the aldosterone after ACTH stimulation was effective for distinguishing between unilateral PA and bilateral PA. The diagnostic accuracy was highest at 120 minutes after ACTH stimulation, and the optimal cutoff value of the aldosterone was 77.90 ng/dL, with a sensitivity of 76.8%, a specificity of 87.2%, a positive predictive value of 89.6%, and a negative predictive value of 72.3%. The ACTH stimulation test under 1 mg DST is useful to determine the subtypes of PA, especially in unilateral and bilateral PA, and may guide further treatment in PA patients.

Geomagnetic storms, the Dst ring-current myth and lognormal distributions

USGS Publications Warehouse

Campbell, W.H.

1996-01-01

The definition of geomagnetic storms dates back to the turn of the century when researchers recognized the unique shape of the H-component field change upon averaging storms recorded at low latitude observatories. A generally accepted modeling of the storm field sources as a magnetospheric ring current was settled about 30 years ago at the start of space exploration and the discovery of the Van Allen belt of particles encircling the Earth. The Dst global 'ring-current' index of geomagnetic disturbances, formulated in that period, is still taken to be the definitive representation for geomagnetic storms. Dst indices, or data from many world observatories processed in a fashion paralleling the index, are used widely by researchers relying on the assumption of such a magnetospheric current-ring depiction. Recent in situ measurements by satellites passing through the ring-current region and computations with disturbed magnetosphere models show that the Dst storm is not solely a main-phase to decay-phase, growth to disintegration, of a massive current encircling the Earth. Although a ring current certainly exists during a storm, there are many other field contributions at the middle-and low-latitude observatories that are summed to show the 'storm' characteristic behavior in Dst at these observatories. One characteristic of the storm field form at middle and low latitudes is that Dst exhibits a lognormal distribution shape when plotted as the hourly value amplitude in each time range. Such distributions, common in nature, arise when there are many contributors to a measurement or when the measurement is a result of a connected series of statistical processes. The amplitude-time displays of Dst are thought to occur because the many time-series processes that are added to form Dst all have their own characteristic distribution in time. By transforming the Dst time display into the equivalent normal distribution, it is shown that a storm recovery can be predicted with remarkable accuracy from measurements made during the Dst growth phase. In the lognormal formulation, the mean, standard deviation and field count within standard deviation limits become definitive Dst storm parameters.

NON-DESTRUCTIVE METHOD AND MEANS FOR FLAW DETECTION

DOEpatents

Hochschild, R.

1959-03-10

BS>An improved method is presented for the nondestructive detection of flaws in olectrictilly conductivc articles using magnetic field. According to thc method a homogoneous mignetic field is established in the test article;it right angle" to the artyicle. A probe is aligned with its axis transverse to the translates so hat th4 probe scans the surface of the test article while the axis of the robe is transverse to the direction of translation of the article. In this manner any output current obtained in thc probe is an indication of the size and location of a flaw in the article under test, with a miiiimum of signal pick- up in the probe from the established magnetic field.

Postmortem redistribution of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH)

PubMed Central

Holland, Michael G.; Schwope, David M.; Stoppacher, Robert; Gillen, Shane B.; Huestis, Marilyn A.

2012-01-01

Introduction Postmortem redistribution (PMR), a well-described phenomenon in forensic toxicology for certain drugs, can result in increased central blood concentrations relative to peripheral blood concentrations. Δ9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis or marijuana, is the illicit substance most commonly implicated in driving under the influence of drugs (DUID) cases and fatally-injured drivers. No investigation of PMR of THC in human blood has been reported to date. Methods Matched heart and iliac postmortem blood specimens were collected from 19 medical examiner cases (16 Males, 3 Females) with positive cannabinoid urine immunoassay screens. THC, its equipotent metabolite 11-hydroxy-THC (11-OH-THC) and non-psychoactive metabolite 11-nor-9-carboxy-THC (THCCOOH) were quantified by two-dimensional gas chromatography-mass spectrometry with cryofocusing, with 0.5 ng/mL limits of quantification (LOQ) for all analytes. Results 10 cases had quantifiable THC and 11-OH-THC; THCCOOH was present in all 19. Median (range) heart:iliac blood ratios were 1.5 for THC (range: 0.3–3.1); 1.6 for 11-OH-THC (range: 0.3–2.7); and 1.8 for THCCOOH (range: 0.5–3.0). Discussion Cannabinoids, in general, exhibited a mean and median central: peripheral (C: P) concentration ratio of less than 2 following death. A trend was observed for greater PMR with increasing postmortem interval between death and sampling. To our knowledge, these are the first data on THC PMR in humans, providing important scientific data to aid in the interpretation of postmortem cannabinoid concentrations in medico-legal investigations. PMID:21764230

Comparison of Xpert MTB/RIF Assay and GenoType MTBDRplus DNA Probes for Detection of Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis.

PubMed

Rahman, Arfatur; Sahrin, Mahfuza; Afrin, Sadia; Earley, Keith; Ahmed, Shahriar; Rahman, S M Mazidur; Banu, Sayera

2016-01-01

GeneXpert MTB/RIF (Xpert) and Genotype MTBDRplus (DRplus) are two World Health Organization (WHO) endorsed probe based molecular drug susceptibility testing (DST) methods for rapid diagnosis of drug resistant tuberculosis. Both methods target the same 81 bp Rifampicin Resistance Determining Region (RRDR) of bacterial RNA polymerase β subunit (rpoB) for detection of Rifampicin (RIF) resistance associated mutations using DNA probes. So there is a correspondence of the probes of each other and expected similarity of probe binding. We analyzed 92 sputum specimens by Xpert, DRplus and LJ proportion method (LJ-DST). We compared molecular DSTs with gold standard LJ-DST. We wanted to see the agreement level of two molecular methods for detection of RIF resistance associated mutations. The 81bp RRDR region of rpoB gene of discrepant cases between the two molecular methods was sequenced by Sanger sequencing. The agreement of Xpert and DRplus with LJ-DST for detection of RIF susceptibility was found to be 93.5% and 92.4%, respectively. We also found 92.4% overall agreement of two molecular methods for the detection of RIF susceptibility. A total of 84 out of 92 samples (91.3%) had agreement on the molecular locus of RRDR mutation by DRplus and Xpert. Sanger sequencing of 81bp RRDR revealed that Xpert probes detected seven of eight discrepant cases correctly and DRplus was erroneous in all the eight cases. Although the overall concordance with LJ-DST was similar for both Xpert and DRplus assay, Xpert demonstrated more accuracy in the detection of RIF susceptibility for discrepant isolates compared with DRplus. This observation would be helpful for the improvement of probe based detection of drug resistance associated mutations especially rpoB mutation in M. tuberculosis.

Oral fluid cannabinoids in chronic frequent cannabis smokers during ad libitum cannabis smoking

PubMed Central

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

2014-01-01

Background Oral fluid (OF) offers a simple, non-invasive and directly observable sample collection for clinical and forensic drug testing. Given that chronic cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum smoking is important for practical development of analytical methods and informed interpretation of test results. Methods Eleven cannabis smokers resided on a closed research unit for 51 days, and underwent four 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9 days of ad libitum cannabis smoking from 12:00 to 23:00h daily. Ten OF samples were collected from 9:00–22:00h on each of the last ad libitum smoking days (Study Days 4, 18, 32, and 46). Results As the number of cannabis cigarettes smoked increased over study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last smoking (∆time; range, 0.0–17.4h) and ≥88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30 min post smoking, median THC, CBN, and THCCOOH concentrations were 689µg/L, 116µg/L, and 147ng/L, respectively, decreasing to 19.4µg/L, 2.4µg/L, and 87.6ng/L after 10h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Conclusions Cannabinoid disposition in OF was highly influenced by ∆time and composition of smoked cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum smoking days, in parallel with increased cannabis self-administration, possibly reflecting development of increased cannabis tolerance. PMID:25220020

Lost sleep and cyberloafing: Evidence from the laboratory and a daylight saving time quasi-experiment.

PubMed

Wagner, David T; Barnes, Christopher M; Lim, Vivien K G; Ferris, D Lance

2012-09-01

The Internet is a powerful tool that has changed the way people work. However, the ubiquity of the Internet has led to a new workplace threat to productivity-cyberloafing. Building on the ego depletion model of self-regulation, we examine how lost and low-quality sleep influence employee cyberloafing behaviors and how individual differences in conscientiousness moderate these effects. We also demonstrate that the shift to Daylight Saving Time (DST) results in a dramatic increase in cyberloafing behavior at the national level. We first tested the DST-cyberloafing relation through a national quasi-experiment, then directly tested the relation between sleep and cyberloafing in a closely controlled laboratory setting. We discuss the implications of our findings for theory, practice, and future research.

Validating a Spanish Developmental Spelling Test.

ERIC Educational Resources Information Center

Ferroli, Lou; Krajenta, Marilyn

The creation and validation of a Spanish version of an English developmental spelling test (DST) is described. An introductory section reviews related literature on the rationale for and construction of DSTs, spelling development in the early grades, and Spanish-English bilingual education. Differences between the English and Spanish test versions…

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).

Large Eddy Simulations using oodlesDST

DTIC Science & Technology

2016-01-01

Research Agency DST-Group-TR-3205 ABSTRACT The oodlesDST code is based on OpenFOAM software and performs Large Eddy Simulations of......maritime platforms using a variety of simulation techniques. He is currently using OpenFOAM software to perform both Reynolds Averaged Navier-Stokes

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.

Exposure to marijuana smoke impairs memory retrieval in mice.

PubMed

Niyuhire, Floride; Varvel, Stephen A; Martin, Billy R; Lichtman, Aron H

2007-09-01

Marijuana (Cannabis sativa) and its primary psychoactive component, delta-9-tetrahydrocannabinol (Delta(9)-THC), have long been known to disrupt cognition in humans. Although Delta(9)-THC and other cannabinoids disrupt performance in a wide range of animal models of learning and memory, few studies have investigated the effects of smoked marijuana in these paradigms. Moreover, in preclinical studies, cannabinoids are generally administered before acquisition, and because retention is generally evaluated soon afterward, it is difficult to distinguish between processes related to acquisition and retrieval. In the present study, we investigated the specific effects of marijuana smoke and injected Delta(9)-THC on acquisition versus memory retrieval in a mouse repeated acquisition Morris water-maze task. To distinguish between these processes, subjects were administered Delta(9)-THC or they were exposed to marijuana smoke either 30 min before acquisition or 30 min before the retention test. Inhalation of marijuana smoke or injected Delta(9)-THC impaired the ability of the mice to learn the location of the hidden platform and to recall the platform location once learning had already taken place. In contrast, neither drug impaired performance in a cued task in which the platform was made visible. Finally, the cannabinoid-1 (CB(1)) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (rimonabant) blocked the memory disruptive effects of both Delta(9)-THC and marijuana. These data represent the first evidence demonstrating that marijuana impairs memory retrieval through a CB(1) receptor mechanism of action and independently of its effects on sensorimotor performance, motivation, and initial acquisition.

Longitudinal observation of [11C]4DST uptake in turpentine-induced inflammatory tissue.

PubMed

Toyohara, Jun; Sakata, Muneyuki; Oda, Keiichi; Ishii, Kenji; Ishiwata, Kiichi

2013-02-01

Longitudinal changes of 4'-[methyl-(11)C]thiothymidine ([(11)C]4DST) uptake were evaluated in turpentine-induced inflammation. Turpentine (0.1 ml) was injected intramuscularly into the right hind leg of male Wistar rats. Longitudinal [(11)C]4DST uptake was evaluated by the tissue dissection method at 1, 2, 4, 7, and 14 days after turpentine injection (n=5). The tumor selectivity index was calculated using the previously published biodistribution data in C6 glioma-bearing rats. Dynamic PET scan was performed on day 4 when maximum [(11)C]4DST uptake was observed during the longitudinal study. Histopathological analysis and Ki-67 immunostaining were also performed. The uptake of [(11)C]4DST in inflammatory tissue was significantly increased on days 2-4 after turpentine injection, and then decreased. On day 14, tracer uptake returned to the day 1 level. The maximum SUV of inflamed muscle was 0.6 and was 3 times higher than that of the contralateral healthy muscle on days 2-4 after turpentine injection. However, tumor selectivity index remains very high (>10) because of the low inflammation uptake. A dynamic PET scan showed that the radioactivity in inflammatory tissues peaked at 5 min after [(11)C]4DST injection, and then washed out until 20 min. At intervals >20 min, radioactivity levels were constant and double that of healthy muscle. The changes in Ki-67 index were paralleled with those of [(11)C]4DST uptake, indicating cell proliferation-dependent uptake of [(11)C]4DST in inflammatory tissues. In our animal model, low but significant levels of [(11)C]4DST uptake were observed in subacute inflammation. Copyright © 2013 Elsevier Inc. 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 ability to trigger different region-dependent changes in glutamate synapse and glial cells. The phenotype observed in males is mainly associated with marked dysregulations in the hippocampus, whereas the prevalence of alterations in the emotional sphere in females is associated with profound changes in the PFC. Copyright © 2016 Elsevier Ltd. All rights reserved.

40 CFR 1065.303 - Summary of required calibration and verifications

Code of Federal Regulations, 2010 CFR

2010-07-01

.... THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: Upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers.... For THC FID analyzers: Upon initial installation, after major maintenance, and after FID optimization...

40 CFR 1065.303 - Summary of required calibration and verifications

Code of Federal Regulations, 2011 CFR

2011-07-01

.... THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: Upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers.... For THC FID analyzers: Upon initial installation, after major maintenance, and after FID optimization...

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

DTIC Science & Technology

1929-08-01

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

Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys.

PubMed

ElSohly, M A; Stanford, D F; Harland, E C; Hikal, A H; Walker, L A; Little, T L; Rider, J N; Jones, A B

1991-10-01

Oral administration of delta-9-tetrahydrocannabinal (delta 9-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. delta 9-THC-Hemisuccinate was formulated as a prodrug for delta 9-THC in suppositories using Witepsol H15 base. The bioavailability of delta 9-THC from this formulation was evaluated in monkeys. The plasma levels of delta 9-THC and its metabolite 11-nor-delta 9-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of delta 9-THC from this formulation was found to be 13.5%. Non-compartmental analysis of the plasma concentration data using statistical moments showed the mean residence time (MRT) for delta 9-THC in the body to be 3 h following iv administration of delta 9-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the delta 9-THC hemisuccinate. The observed rectal bioavailability of delta 9-THC from suppositories containing the hemisuccinate ester as a prodrug is of significant importance in developing an alternative approach to oral administration of the drug.

Separate and combined effects of gabapentin and Δ9-THC in humans discriminating Δ9-THC

PubMed Central

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

2015-01-01

The aim of the present study was to examine a potential mechanism of action of gabapentin to manage cannabis-use disorders by determining the interoceptive effects of gabapentin in cannabis users discriminating Δ9-THC using a pharmacologically selective drug-discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received gabapentin (600 and 1200 mg), Δ9-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Δ9-THC served as a discriminative stimulus, produced positive subjective effects, elevated heart rate and impaired psychomotor performance. Both doses of gabapentin substituted for the Δ9-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Δ9-THC when administered alone. When administered concurrently, gabapentin shifted the discriminative-stimulus effects of Δ9-THC leftward/upward, and combinations of Δ9-THC and gabapentin generally produced larger effects on cannabinoid-sensitive outcomes relative to Δ9-THC alone. These results suggest that one mechanism by which gabapentin might facilitate cannabis abstinence is by producing effects that overlap with those of cannabinoids. PMID:26313650

Does Daylight Savings Time encourage physical activity?

PubMed

Zick, Cathleen D

2014-07-01

Extending Daylight Savings Time (DST) has been identified as a policy intervention that may encourage physical activity. However, there has been little research on the question of if DST encourages adults to be more physically active. Data from residents of Arizona, Colorado, New Mexico, and Utah ages 18-64 who participated in the 2003-2009 American Time Use Survey are used to assess whether DST is associated with increased time spent in moderate-to-vigorous physical activity (MVPA). The analysis capitalizes on the natural experiment created because Arizona does not observe DST. Both bivariate and multivariate analyses indicate that shifting 1 hour of daylight from morning to evening does not impact MVPA of Americans living in the southwest. While DST may affect the choices people make about the timing and location of their sports/recreational activities, the potential for DST to serve as a broad-based intervention that encourages greater sports/recreation participation is not supported by this analysis. Whether this null effect would persist in other climate situations is an open question.

Time Delay Between Dst Index and Magnetic Storm Related Structure in the Solar Wind

NASA Technical Reports Server (NTRS)

Osherovich, Vladimir A.; Fainberg, Joseph

2015-01-01

Benson et al. (2015, this volume) selected 10 large magnetic storms, with associated Dst minimum values less than or equal to -100 nT, for which high-latitude topside ionospheric electron density profiles are available from topside-sounder satellites. For these 10 storms, we performed a superposition of Dst and interplanetary parameters B, v, N(sub p) and T(sub p). We have found that two interplanetary parameters, namely B and v, are sufficient to reproduce Dst with correlation coefficient cc approximately 0.96 provided that the interplanetary parameter times are taken 0.15 days earlier than the associated Dst times. Thus we have found which part of the solar wind is responsible for each phase of the magnetic storm. This result is also verified for individual storms as well. The total duration of SRS (storm related structure in the solar wind) is 4 - 5 days which is the same as the associated Dst interval of the magnetic storm.

Core competencies to prevent and control chronic diseases of Tambol Health Centers' head in Thailand.

PubMed

Leerapan, Prasit; Kengganpanich, Tharadol; Sompopcharoen, Malinee

2012-06-01

To assess the core competencies to prevent and control chronic diseases of the head of Tambol Health Centers (THC) in Thailand. This cross-sectional survey research was carried out with 2,049 heads of THC from the total population of 9,985. The samples were selected randomly from all provinces of every region. The data were collected through mail questionnaires and the reliability values of the three competency domains questionnaire were found to be between 0.75-0.93. Data analysis was done by computing frequency, percentage, arithmetic mean, Independent's t-test and One-way ANOVA. The total core competency values of prevention and control of diabetes and hypertension of the THC heads were found at the high and moderate level (3.0% and 78.7%) respectively The similar finding was found in the competency domains in regard to "personal attribution", "intellectual capacity" while 8.0 percent and 46.2 percent of the respondents had the high and moderate level of "work skill" domain respectively. In addition, the differences of competency domains were found in accordance with the regions where the THC located, ability to develop a plan for disease prevention and readiness for changing behaviors of the risk groups. But the personal attributions with regard to gender age, family's economic status, and the location of the THC were not found to affect every competency domain. Except for the intellectual capacity domain found that the male THC heads had the higher level than the females and work skill domain of those THC heads working in the municipal areas had the higher level than those who worked outside the municipal areas. Core competencies of the heads of THC in chronic disease prevention and control were found at the "somewhat good" level except for the work skill domain which needed to be developed. Thus, the Ministry of Public Health should establish a specific policy and strategy on human resource development by using core competencies on chronic disease prevention and control as the core performance indicators.

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

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

Monnet-Tschudi, Florianne; Hazekamp, Arno; Perret, Nicolas

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

Tetrahydrocannabinols in clinical and forensic toxicology.

PubMed

Kochanowski, Maciej; Kała, Maria

2005-01-01

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

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

PubMed Central

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

2014-01-01

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

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.

Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death.

PubMed

Armstrong, Jane L; Hill, David S; McKee, Christopher S; Hernandez-Tiedra, Sonia; Lorente, Mar; Lopez-Valero, Israel; Eleni Anagnostou, Maria; Babatunde, Fiyinfoluwa; Corazzari, Marco; Redfern, Christopher P F; Velasco, Guillermo; Lovat, Penny E

2015-06-01

Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain <10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wild-type tumors. Targeting autophagy is a means to promote cancer cell death in chemotherapy-resistant tumors, and the aim of this study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma. Treatment with Δ(9)-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette.

PubMed

Marsot, Amélie; Audebert, Christine; Attolini, Laurence; Lacarelle, Bruno; Micallef, Joelle; Blin, Olivier

A randomized cross-over, double blind placebo controlled study of smoked cannabis was carried out on occasional cannabis smokers. The objective of this research was to describe the pharmacokinetic parameters of THC and its metabolites in plasma, oral fluid and urine, from samples obtained simultaneously to provide estimations of THC and metabolites concentrations after smoking a cannabis cigarette. Blood, oral fluid and urine samples were collected until up to 72 h after smoking the cannabis cigarette (4% of delta-9-tetrathydrocannabinol (THC)). THC, 11-OH-THC and THC-COOH were analyzed by gas-chromatography-mass spectrometry. Pharmacokinetic parameters were estimated from these data. Eighteen male healthy adults participated in the study. In total, 560 plasma, 288 oral fluid and 448 urine samples were quantified for cannabinoids. Plasma, oral fluid and urine pharmacokinetic parameters were calculated. A wide range of median THC Cmax (1.6-160.0 µg/L and 55.4-123120.0 µg/L in plasma and oral fluid, respectively), 11-OH-THC Cmax (0-11.1 µg/L in plasma) and THC-COOH Cmax (1.0-56.3 µg/L in plasma) was observed. When expressed as a percentage of the total available THC dose, and corrected for molar equivalents, mean percentage of total THC dose excreted was 1.9 +/-2.5 % with range of 0.2-7.5%. This high inter-individual variability was also observed on other calculated pharmacokinetic parameters. Prediction of plasma THC concentration from THC oral fluid concentration or from THC-COOH urinary concentrations is not feasible due to the large variations observed. The results from this study support the assumption that a positive oral fluid THC result or a positive urine fluid result are indicative of a recent cannabis exposure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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

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.

DEVICE FOR TREATING MATERIALS

DOEpatents

Ohlinger, L.A.; Seitz, F.; Young, G.J.

1959-02-17

Test-hole construction in a reactor to facilitate inserting and removing test specimens from the reactor for irradiation therein is discussed. An elongated chamber extends from the outer face of the reactor shield into the reactor. A shield box, having an open end, is sealed to thc outer face of the reactor shield by its open end surrounding the outer end of the chamber. A removable door is provided in the side wall of the shield box for inscrtion and removal of test specimens. A means operable from thc exterior of the shield box is provided for transferring test specimens between the shield box and the irradiation position within the chamber and consists of an elongated rod having a specimen tray engaging member on its inner end, which may be manipulated by the operator.

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.

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

Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex®): A Review in Multiple Sclerosis-Related Spasticity.

PubMed

Keating, Gillian M

2017-04-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (THC/CBD, Sativex ® , nabiximols) is available in numerous countries worldwide for the treatment of multiple sclerosis (MS)-related moderate to severe spasticity in patients who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. Twelve weeks' therapy with THC/CBD improved MS-related spasticity in patients with an inadequate response to other anti-spasticity agents who had undergone a successful initial trial of THC/CBD therapy, according to the results of a pivotal phase 3 trial. Improvements in spasticity were maintained in the longer term with THC/CBD with no evidence of dose tolerance, and results of real-world studies confirm the effectiveness of THC/CBD in everyday clinical practice. Improvements in health-related quality of life and activities of daily living were also seen with THC/CBD. THC/CBD is generally well tolerated; adverse effects such as dizziness may occur whilst the THC/CBD dosage is being optimized. THC/CBD has low abuse potential and a low risk of psychoactive effects. In conclusion, THC/CBD oromucosal spray is a useful option for the treatment of MS-related spasticity not completely relieved with current anti-spasticity medication.

Leptospirosis outbreak following severe flooding: a rapid assessment and mass prophylaxis campaign; Guyana, January-February 2005.

PubMed

Dechet, Amy M; Parsons, Michele; Rambaran, Madan; Mohamed-Rambaran, Pheona; Florendo-Cumbermack, Anita; Persaud, Shamdeo; Baboolal, Shirematee; Ari, Mary D; Shadomy, Sean V; Zaki, Sherif R; Paddock, Christopher D; Clark, Thomas A; Harris, Lazenia; Lyon, Douglas; Mintz, Eric D

2012-01-01

Leptospirosis is a zoonosis usually transmitted through contact with water or soil contaminated with urine from infected animals. Severe flooding can put individuals at greater risk for contracting leptospirosis in endemic areas. Rapid testing for the disease and large-scale interventions are necessary to identify and control infection. We describe a leptospirosis outbreak following severe flooding and a mass chemoprophylaxis campaign in Guyana. From January-March 2005, we collected data on suspected leptospirosis hospitalizations and deaths. Laboratory testing included anti-leptospiral dot enzyme immunoassay (DST), immunohistochemistry (IHC) staining, and microscopic agglutination testing (MAT). DST testing was conducted for 105 (44%) of 236 patients; 52 (50%) tested positive. Four (57%) paired serum samples tested by MAT were confirmed leptospirosis. Of 34 total deaths attributed to leptospirosis, postmortem samples from 10 (83%) of 12 patients were positive by IHC. Of 201 patients interviewed, 89% reported direct contact with flood waters. A 3-week doxycycline chemoprophylaxis campaign reached over 280,000 people. A confirmed leptospirosis outbreak in Guyana occurred after severe flooding, resulting in a massive chemoprophylaxis campaign to try to limit morbidity and mortality.

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

Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration.

PubMed

Karschner, Erin L; Darwin, W David; Goodwin, Robert S; Wright, Stephen; Huestis, Marilyn A

2011-01-01

Sativex(®), a cannabis extract oromucosal spray containing Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor- 9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were ≤0.25 μg/L. Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C(max)) and areas under the curve from 0-10.5 h postdose (AUC(0→10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C(max), time to maximum concentration or in the AUC(0→10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.

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.

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.

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.

Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis.

PubMed

Todd, S M; Arnold, J C

2016-01-01

It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Δ(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC. However, our understanding of CBD and THC interactions is limited and the brain circuitry mediating interactions between CBD and THC are unknown. The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols. Male C57BL/6 mice were treated with vehicle, CBD, THC or a combination of CBD and THC (10 mg·kg(-1) i.p. for both cannabinoids) to examine effects on locomotor activity, anxiety-related behaviour, body temperature and brain c-Fos expression (a marker of neuronal activation). CBD potentiated THC-induced locomotor suppression but reduced the hypothermic and anxiogenic effects of THC. CBD alone had no effect on these measures. THC increased brain activation as measured by c-Fos expression in 11 of the 35 brain regions studied. CBD co-administration suppressed THC-induced c-Fos expression in six of these brain regions. This effect was most pronounced in the medial preoptic nucleus and lateral periaqueductal gray. Treatment with CBD alone diminished c-Fos expression only in the central nucleus of the amygdala compared with vehicle. These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC. © 2015 The British Pharmacological Society.

Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake.

PubMed

Newmeyer, Matthew N; Swortwood, Madeleine J; Barnes, Allan J; Abulseoud, Osama A; Scheidweiler, Karl B; Huestis, Marilyn A

2016-12-01

There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ 9 -tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ 9 -tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513. © 2016 American Association for Clinical Chemistry.

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.

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.

Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

PubMed

Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

2009-08-01

Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

Disposition of Cannabichromene, Cannabidiol, and Δ9-Tetrahydrocannabinol and its Metabolites in Mouse Brain following Marijuana Inhalation Determined by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

PubMed Central

Poklis, Justin L.; Thompson, Candace C.; Long, Kelly A.; Lichtman, Aron H.; Poklis, Alphonse

2011-01-01

A liquid chromatography–tandem mass spectrometry (LC–MS–MS) method was developed for the analysis of marijuana cannabinoids in mouse brain tissue using an Applied Biosystems 3200 Q trap with a turbo V source for TurbolonSpray attached to a Shimadzu SCL HPLC system. The method included cannabichromene (CBC), cannabidiol (CBD), D9-tetrahydrocannabinol (THC), 11-hydroxytetrahydrocannabinol (11-OH-THC), and 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). These compounds were isolated by liquid-liquid extraction using cold acetonitrile. The following transition ions were monitored by multiple reaction monitoring (MRM): m/z 315>193, 315>259 for THC/CBD/CBC; m/z 331>193, 331>105 for 11-OH-THC; m/z 345>299, 345>193 for THC-COOH;c m/z 318>196 for THC-d3; m/z 334>196 for 11-OH-THC-d3, and m/z 348>302 for THCCOOH-d3. Linearity for THC, 1-OH-THC, and THC-COOH was 1-200 ng/g; for CBC and CBD, it was 0.5–20 ng/g. Within-run and between-run precisions for all the analytes yielded coefficients of variation of < 20%. Four C57BL6 mice were sacrificed 20 min after nose-only exposure to the smoke of 200 mg of marijuana containing 0.44 mg CBC, 0.93 mg CBD, and 8.81 mg THC. The mean brain concentrations were 3.9 ± 1.5 ng/g CBC, 21 ± 3.9 ng/g CBD, 364 ± 74 ng/g THC, and 28 ± 5.9 ng/g 11-OH-THC. THCCOOH was not detected. The relative mean brain cannabinoid concentrations correlated to the amounts of the cannabinoids in the inhaled marijuana. PMID:21258613

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity

NASA Astrophysics Data System (ADS)

Song, Chenchen; Martínez, Todd J.

2016-05-01

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N2.6 for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 are less than 0.5 kcal/mol for all systems tested (up to 162 atoms).

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity.

PubMed

Song, Chenchen; Martínez, Todd J

2016-05-07

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N(2.6) for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 are less than 0.5 kcal/mol for all systems tested (up to 162 atoms).

Simultaneous quantification of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry

PubMed Central

Lowe, Ross H.; Karschner, Erin L.; Schwilke, Eugene W.; Barnes, Allan J.; Huestis, Marilyn A.

2009-01-01

A two-dimensional (2D) gas chromatography/electron impact-mass spectrometry (GC/EI-MS) method for simultaneous quantification of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in human plasma was developed and validated. The method employs 2D capillary GC and cryofocusing for enhanced resolution and sensitivity. THC, 11-OH-THC, and THCCOOH were extracted by precipitation with acetonitrile followed by solid-phase extraction. GC separation of trimethylsilyl derivatives of analytes was accomplished with two capillary columns in series coupled via a pneumatic Deans switch system. Detection and quantification were accomplished with a bench-top single quadrupole mass spectrometer operated in electron impact-selected ion monitoring mode. Limits of quantification (LOQ) were 0.125, 0.25 and 0.125 ng/mL for THC, 11-OH-THC, and THCCOOH, respectively. Accuracy ranged from 86.0 to 113.0% for all analytes. Intra- and inter-assay precision, as percent relative standard deviation, was less than 14.1% for THC, 11-OH-THC, and THCCOOH. The method was successfully applied to quantification of THC and its 11-OH-THC and THCCOOH metabolites in plasma specimens following controlled administration of THC. PMID:17640656

Swallowing disorders in nursing home residents: how can the problem be explained?

PubMed Central

Nogueira, Dália; Reis, Elizabeth

2013-01-01

Background The swallowing mechanism changes significantly as people age, even in the absence of chronic diseases. Presbyphagia, a term that refers to aging-related changes in the swallowing mechanism, may be linked to many health conditions and presents itself in distinct ways. Swallowing disorders are also identified as a major problem amongst the elderly population living in nursing homes. Methods The study sought to determine the prevalence of swallowing disorders in nursing home residents, to identify the relationship between self-perceived swallowing disorders, cognitive functions, autonomy, and depression, and also to analyze which variables explain the score of the Dysphagia Self-Test (DST). For this purpose, the researchers chose to apply a survey conveying questions on demographic aspects, general health, eating and feeding, as well as instruments to assess functional performance and the 3 ounce Water Swallow Test. Results The sample consisted of 272 elderly people living in eight nursing homes in Portugal. Six did not sign the informed consent form. Of the total, 29% were totally dependent, 33% were depressed, 45% had cognitive impairment, and 38% needed help with feeding. About 43% of the individuals reported having problems related to eating. Regarding the DST, 40% showed signs of dysphagia. With respect to the 3 ounce Water Swallow Test, 38% revealed at least one of the symptoms, wet voice being the most prevalent. Correlation measures showed that age had no linear association with the DST score although correlation with the Barthel Index and Mini Mental State Examination was found to be significant. A linear regression model was estimated with the DST score as the dependent variable and the MMSE and BI scores, gender, age, education, the Geriatric Depression Scale score, 3 ounce Water Swallow Test, and diagnosed conditions (such as neurological disorder, dementia, and cardiorespiratory problems) as explaining variables. Conclusion Results showed a high prevalence of dysphagia signs amongst a nursing home population. For the purpose of the present study, both a subjective and an objective assessment were applied. Results pointed to a significant statistical relation between objective and subjective measures, thus indicating that a self-perception test should be included in the assessment of swallowing disorders in a nursing home population. Notwithstanding, it should not be used as a single or principal measure as it is influenced by the individuals’ cognitive condition. PMID:23449951

Effect of hydrolysis on identifying prenatal cannabis exposure

PubMed Central

Gray, Teresa R.; Barnes, Allan J.

2011-01-01

Identification of prenatal cannabis exposure is important due to potential cognitive and behavioral consequences. A two-dimensional gas chromatography–mass spectrometry method for cannabinol, Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 8β,11-dihydroxy-THC, and 11-nor-9-carboxy-THC (THCCOOH) quantification in human meconium was developed and validated. Alkaline, enzymatic, and enzyme–alkaline tandem hydrolysis conditions were optimized with THC- and THCCOOH-glucuronide reference standards. Limits of quantification ranged from 10 to 15 ng/g, and calibration curves were linear to 500 ng/g. Bias and intra-day and inter-day imprecision were <12.3%. Hydrolysis efficiencies were analyte-dependent; THC-glucuronide was effectively cleaved by enzyme, but not base. Conversely, THCCOOH-glucuronide was most sensitive to alkaline hydrolysis. Enzyme–alkaline tandem hydrolysis maximized efficiency for both glucuronides. Identification of cannabinoid-positive meconium specimens nearly doubled following alkaline and enzyme–alkaline hydrolysis. Although no 11-OH-THC glucuronide standard is available, enzymatic hydrolysis improved 11-OH-THC detection in authentic specimens. Maximal identification of cannabis-exposed neonates and the widest range of cannabis biomarkers are achieved with enzyme–alkaline tandem hydrolysis. PMID:20517601

Dynamic surface tension measurement for the screening of biosurfactants produced by Lactobacillus plantarum subsp. plantarum PTCC 1896.

PubMed

Bakhshi, Nafiseh; Soleimanian-Zad, Sabihe; Sheikh-Zeinoddin, Mahmoud

2017-06-01

Currently, screening of microbial biosurfactants (BSs) is based on their equilibrium surface tension values obtained using static surface tension measurement. However, a good surfactant should not only have a low equilibrium surface tension, but its dynamic surface tension (DST) should also decrease rapidly with time. In this study, screening of BSs produced by Lactobacillus plantarum subsp. plantarum PTCC 1896 (probiotic) was performed based on their DST values measured by Wilhelmy plate tensiometry. The relationship between DST and structural and functional properties (anti-adhesive activity) of the BSs was investigated. The results showed that the changes in the yield, productivity and structure of the BSs were growth medium and incubation time dependent (p<0.05). Structurally different BSs produced exhibited identical equilibrium surface tension values. However, differences among the structure/yield of the BSs were observed through the measurement of their DST. The considerable dependence of DST on the concentration and composition of the BS proteins was observed (p<0.05). Moreover, the anti-adhesive activity of the BS was found to be positively correlated with its DST. The results suggest that the DST measurement could serve as an efficient method for the clever screening of BSs producer/production condition, and consequently, for the investigation of probiotic features of bacteria, since the anti-adhesive activity is an important criterion of probiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

Drug and alcohol testing results 1996 annual report

DOT National Transportation Integrated Search

1997-12-01

The report is a compilation and analysis of mass transit drug and alcohol testing reported by transit systems in the United States during 1996. The report covers testing results for the following drug types: marijuana (THC), cocaine, phencyclidine (P...

Drug and Alcohol Testing Results - 1995 Annual Report

DOT National Transportation Integrated Search

1997-03-01

The Report is a compilation and analysis of mass transit drug and alcohol testing reported by transit systems in the United States during 1995. The report covers testing for alcohol and the following drug types: marijuana (THC), cocaine, phencyclidin...

The Dexamethasone Suppression Test as an Indication of Depression in Patients with Mental Retardation.

ERIC Educational Resources Information Center

Mattes, Jeffrey A.; Amsell, Loren

1993-01-01

Administration of the Dexamethasone Suppression Test (DST) for three groups of institutionalized patients with severe/profound mental retardation found that the 12 depressed patients more frequently (though not significantly) had positive DSTs and significantly higher cortisol levels compared with nondepressed patients with and without other…

Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice

PubMed Central

Busquets-Garcia, Arnau; Soria-Gómez, Edgar; Redon, Bastien; Mackenbach, Yarmo; Chaouloff, Francis; Varilh, Marjorie; Ferreira, Guillaume; Piazza, Pier-Vincenzo; Marsicano, Giovanni

2017-01-01

Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side-effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy. The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. In order to capture THC-induced positive psychotic-like symptoms (e.g. perceptual delusions), we adapted a behavioral paradigm based on associations between different sensory modalities and selective devaluation, allowing the measurement of mental sensory representations in mice. Acting at hippocampal CB1 receptors, THC impaired the correct processing of mental sensory representations (reality testing) in an antipsychotic- and pregnenolone-sensitive manner. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS. PMID:28220044

Personal Voices in Higher Education: A Digital Storytelling Experience for Pre-Service Teachers

ERIC Educational Resources Information Center

Kocaman-Karoglu, Aslihan

2016-01-01

Digital storytelling (DST) has recently emerged as a new tool in instructional environments. DST involves the combination of media and technology with traditional storytelling to help students learn. This paper examines the use of DST in a university course and pre-service teachers' perceptions of their learning experiences using this tool.…

Co-expression of tetanus toxin fragment C in Escherichia coli with thioredoxin and its evaluation as an effective subunit vaccine candidate.

PubMed

Yu, Yun-Zhou; Gong, Zheng-Wei; Ma, Yao; Zhang, Shu-Ming; Zhu, Heng-Qi; Wang, Wen-Bing; Du, Yun; Wang, Shuang; Yu, Wei-Yuan; Sun, Zhi-Wei

2011-08-11

The receptor-binding domain of tetanus toxin (THc), which mediates the binding of the toxin to the nerve cells, is a candidate subunit vaccine against tetanus. In this study one synthetic gene encoding the THc was constructed and highly expressed in Escherichia coli by co-expression with thioredoxin (Trx). The purified THc-vaccinated mice were completely protected against an active toxin challenge in mouse models of disease and the potency of two doses of THc was comparable to that of three doses of toxoid vaccine. And a solid-phase assay showed that the anti-THc sera inhibited the binding of THc or toxoid to the ganglioside GT1b as the anti-tetanus toxoid sera. Furthermore, mice were vaccinated once or twice at four different dosages of THc and a dose-response was observed in both the antibody titer and protective efficacy with increasing dosage of THc and number of vaccinations. The data presented in the report showed that the recombinant THc expressed in E. coli is efficacious in protecting mice against challenge with tetanus toxin suggesting that the THc protein may be developed into a human subunit vaccine candidate designed for the prevention of tetanus. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru

PubMed Central

Alarcón, E.; Alarcón, V.; Bissell, K.; Castillo, E.; Sabogal, I.; Mora, J.; Moore, D.; Harries, A. D.

2012-01-01

Setting: Primary health care centres in Callao, Peru. Objectives: To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST). Design: Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008. Results: There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P = 0.003) was observed in the 2009 cohort. Conclusion: Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru. PMID:24579063

Revised Dst and the epicycles of magnetic disturbance: 1958-2007

USGS Publications Warehouse

Love, J.J.; Gannon, J.L.

2009-01-01

A revised version of the storm-time disturbance index Dst is calculated using hourly-mean magnetic-observatory data from four standard observatories and collected over the years 1958-2007. The calculation algorithm is a revision of that established by Sugiura et al., and which is now used by the Kyoto World Data Center for routine production of Dst. The most important new development is for the removal of solar-quiet variation. This is done through time and frequency-domain band-stop filtering - selectively removing specific Fourier terms approximating stationary periodic variation driven by the Earth's rotation, the Moon's orbit, the Earth's orbit around the Sun, and their mutual coupling. The resulting non-stationary disturbance time series are weighted by observatory-site geomagnetic latitude and then averaged together across longitudes to give what we call Dst5807-4SH. Comparisons are made with the standard Kyoto D st. Various biases, especially for residual solar-quiet variation, are identified in the Kyoto Dst, and occasional storm-time errors in the Kyoto Dst are noted. Using Dst5807-4SH, storms are ranked for maximum storm-time intensity, and we show that storm-occurrence frequency follows a power-law distribution with an exponential cutoff. The epicycles of magnetic disturbance are explored: we (1) map low-latitude local-time disturbance asymmetry, (2) confirm the 27-day storm-recurrence phenomenon using autocorrelation, (3) investigate the coupled semi-annual-diurnal variation of magnetic activity and the proposed explanatory equinoctial and Russell-McPherron hypotheses, and (4) illustrate the well-known solar-cycle modulation of storm-occurrence likelihood. Since Dst5807-4SH is useful for a variety of space physics and solid-Earth applications, it is made freely available to the scientific community.

Influence of the substorm current wedge on the Dst index

NASA Astrophysics Data System (ADS)

Friedrich, Erena; Rostoker, Gordon; Connors, Martin G.; McPherron, R. L.

1999-03-01

One of the major questions confronting researchers studying the nature of the solar-terrestrial interaction centers around whether or not the substorm expansive phase has any causal effect on the growth of the storm time ring current. This question is often addressed by using the Dst index as a proxy for the storm time ring current and inspecting the main phase growth of Dst in the context of the substorm expansive phases which occur in the same time frame as the ring current growth. In the past it has been assumed that the magnetic effects of the substorm current wedge have little influence on the Dst index because the current wedge is an asymmetric current system, while Dst is supposed to reflect changes in the symmetric component of the ring current. In this paper we shall shown that the substorm current wedge can have a significant effect on the present Dst index, primarily as a consequence of the fact that only four stations are presently used to formulate the index. Calculations are made assuming the instantaneous magnitude of the wedge current is constant at 1 MA. Hourly values of Dst may be as much as 50° smaller than those presented here because of variation of the wedge current over the hour. We shall show how the effect of the current wedge depends on the UT of the expansive phase onset, the angular extent of the current wedge, and the locale of the closure current in the magnetosphere. The fact that the substorm current wedge is a conjugate phenomenon has an important influence on the magnitude of the expansive phase effect in the Dst index.

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.

A decision support tool for adaptive management of native prairie ecosystems

USGS Publications Warehouse

Hunt, Victoria M.; Jacobi, Sarah; Gannon, Jill J.; Zorn, Jennifer E.; Moore, Clinton; Lonsdorf, Eric V.

2016-01-01

The Native Prairie Adaptive Management initiative is a decision support framework that provides cooperators with management-action recommendations to help them conserve native species and suppress invasive species on prairie lands. We developed a Web-based decision support tool (DST) for the U.S. Fish and Wildlife Service and the U.S. Geological Survey initiative. The DST facilitates cross-organizational data sharing, performs analyses to improve conservation delivery, and requires no technical expertise to operate. Each year since 2012, the DST has used monitoring data to update ecological knowledge that it translates into situation-specific management-action recommendations (e.g., controlled burn or prescribed graze). The DST provides annual recommendations for more than 10,000 acres on 20 refuge complexes in four U.S. states. We describe how the DST promotes the long-term implementation of the program for which it was designed and may facilitate decision support and improve ecological outcomes of other conservation efforts.

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

PubMed

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

2012-05-01

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

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.

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.

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

Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats.

PubMed

Wiley, Jenny L; Lefever, Timothy W; Marusich, Julie A; Craft, Rebecca M

2017-03-01

Women report greater sensitivity to the subjective effects of Δ 9 -tetrahydrocannabinol (THC). Similarly, female rodents tend to be more sensitive to some pharmacological effects of THC and synthetic cannabinoids. This study examined sex differences in discriminative stimulus and response rate effects of THC and synthetic cannabinoids in rats. A cumulative dosing THC discrimination procedure was utilized to evaluate sex differences in the discriminative stimulus effects of THC and three synthetic cannabinoids: CP47,497, WIN55,212-2, and JWH-018. Sex differences in the effects of these four compounds and a degradant of A-834735 on response rates also were assessed in a food-reinforced discrete dosing procedure. Females required a lower training dose than males for acquisition of the discrimination. Further, THC was more potent at producing rimonabant-reversible discriminative stimulus and response rate effects in females. While synthetic cannabinoids were more potent in producing THC-like effects than was THC in female rats, greater discrepancies were observed in male rats. Similar sensitivity to the response rate-decreasing effects induced by most, but not all (A-834735 degradant), synthetic cannabinoids was seen in both sexes. This study represents one of the first direct comparisons of sex differences in THC discrimination. Females were more sensitive to THC's effects, which may be related, in part, to sex differences in THC metabolism. Synthetic cannabinoids were more potent than THC in both sexes, but were considerably more so in male than in female rats. Future research should emphasize further characterization of sex differences in cannabinoid pharmacology. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats.

PubMed

Parker, Linda A; Burton, Page; Sorge, Robert E; Yakiwchuk, Christine; Mechoulam, Raphael

2004-09-01

Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component delta9-tetrahydrocannabinol (delta9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats. To determine the effects of pretreatment with delta9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of delta9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of delta9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of delta9-THC.or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with delta9-THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle. delta9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own. These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning.

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.

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.

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.

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

PubMed

Wilkinson, J D; Whalley, B J; Baker, D; Pryce, G; Constanti, A; Gibbons, S; Williamson, E M

2003-12-01

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

Psychoactive drugs and false memory: comparison of dextroamphetamine and delta-9-tetrahydrocannabinol on false recognition

PubMed Central

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

2014-01-01

Rationale Several psychoactive drugs are known to influence episodic memory. However, these drugs’ effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Objectives Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ9-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger–McDermott (DRM) illusion. Methods Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. Results As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs’ effects on true memory were positively correlated with their effects on false memory. Conclusions Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories. PMID:21647577

Psychoactive drugs and false memory: comparison of dextroamphetamine and δ-9-tetrahydrocannabinol on false recognition.

PubMed

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

2012-01-01

Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood. Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ(9)-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger-McDermott (DRM) illusion. Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions. As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs' effects on true memory were positively correlated with their effects on false memory. Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories.

Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of Δ9-Tetrahydrocannabinolic Acid A.

PubMed

Moreno-Sanz, Guillermo

2016-01-01

Δ 9 -tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ 9 -tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa . THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term "THCA" to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.

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

Cannabis: Exercise performance and sport. A systematic review.

PubMed

Kennedy, Michael C

2017-09-01

To review the evidence relating to the effect of cannabis on exercise performance. A systematic review of published literature METHODS: Tetrahydrocannabinol (THC) is the principal psychoactive component of cannabis. A search was conducted using PUB med, Medline and Embase searching for cannabis, marijuana, cannabinoids and THC, in sport and exercise; the contents of sports medicine journals for the last 10 years; as well as cross references from journals and a personal collection of reprints. Only English language literature was reviewed and only articles that specified the details of a formal exercise program or protocol. Individuals in rehabilitation or health screening programs involving exercise were included as the study may have identified adverse reactions in the marijuana group. Review articles, opinion pieces, policy statements by sporting bodies and regulatory agencies were excluded. Only 15 published studies have investigated the effects of THC in association with exercise protocols. Of these studies, none showed any improvement in aerobic performance. Exercise induced asthma was shown to be inhibited. In terms of detrimental effects, two studies found that marijuana precipitated angina at a lower work-load (100% of subjects) and strength is probably reduced. Some subjects could not complete an exercise protocol because adverse reactions caused by cannabis. An important finding relevant to drug testing was that aerobic exercise was shown to cause only very small rises (<1ng/mL) in THC concentrations. THC does not enhance aerobic exercise or strength. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia.

PubMed

Rowland, Laura M; Summerfelt, Ann; Wijtenburg, S Andrea; Du, Xiaoming; Chiappelli, Joshua J; Krishna, Nithin; West, Jeffrey; Muellerklein, Florian; Kochunov, Peter; Hong, L Elliot

2016-02-01

Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge. To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia. Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015. Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F = 4.39, P = .04) and glutamate (F = 9.69, P = .002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38 [root-mean-square error of approximation, P < .001] by χ2 test), supporting the contention that MMN serves as an intermediate biomarker linking glutamatergic function to DST performance in schizophrenia. The role of glutamate and GABA in MMN and verbal working memory deficits in schizophrenia has been frequently debated. These data provide in vivo evidence that support glutamatergic and GABAergic regulation of MMN and verbal working memory function in schizophrenia.

Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia

PubMed Central

Rowland, Laura M.; Summerfelt, Ann; Wijtenburg, S. Andrea; Du, Xiaoming; Chiappelli, Joshua J.; Krishna, Nithin; West, Jeffrey; Muellerklein, Florian; Kochunov, Peter; Hong, L. Elliot

2016-01-01

IMPORTANCE Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge. OBJECTIVE To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015. MAIN OUTCOMES AND MEASURES Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. RESULTS The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F = 4.39, P = .04) and glutamate (F = 9.69, P = .002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38 [root-mean-square error of approximation, P < .001] by χ2 test), supporting the contention that MMN serves as an intermediate biomarker linking glutamatergic function to DST performance in schizophrenia. CONCLUSIONS AND RELEVANCE The role of glutamate and GABA in MMN and verbal working memory deficits in schizophrenia has been frequently debated. These data provide in vivo evidence that support glutamatergic and GABAergic regulation of MMN and verbal working memory function in schizophrenia. PMID:26720179

40 CFR Table 7 to Subpart Dddd of... - Continuous Compliance With the Compliance Options and Operating Requirements

Code of Federal Regulations, 2012 CFR

2012-07-01

... requirements in Table 2 of this subpart based on THC CEMS data Collecting and recording the THC monitoring data... block average THC concentration in the exhaust gases less than or equal to the THC concentration...

40 CFR Table 7 to Subpart Dddd of... - Continuous Compliance With the Compliance Options and Operating Requirements

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements in Table 2 of this subpart based on THC CEMS data Collecting and recording the THC monitoring data... block average THC concentration in the exhaust gases less than or equal to the THC concentration...

40 CFR Table 7 to Subpart Dddd of... - Continuous Compliance With the Compliance Options and Operating Requirements

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirements in Table 2 of this subpart based on THC CEMS data Collecting and recording the THC monitoring data... block average THC concentration in the exhaust gases less than or equal to the THC concentration...

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 and others have shown for chronic administration during adolescence. Copyright © 2013 Elsevier Inc. All rights reserved.

Occult Cushing's syndrome in type-2 diabetes.

PubMed

Catargi, Bogdan; Rigalleau, Vincent; Poussin, Agathe; Ronci-Chaix, Nathalie; Bex, Veronique; Vergnot, Vincent; Gin, Henri; Roger, Patrick; Tabarin, Antoine

2003-12-01

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.

Accident rates and the impact of daylight saving time transitions.

PubMed

Robb, David; Barnes, Thomas

2018-02-01

One-third of nations have adopted some form of Daylight Saving Time (DST). Associated costs and benefits include impacts on accident rates. Using data from 12.6 million accident claims in New Zealand during 2005-2016, we model accident rates as a function of various date-based predictors including days before/after the start and end of DST, holidays, day of week, and month of year. This is the first study to consider multiple accident categories (Road, Work, Falls and Home & Community), and the first in the southern hemisphere. The start of DST is associated with significantly higher rates of road accidents (first day +16% and second day +12%). Evidence that accident rates for Falls and Home & Community decline (increase) prior to the start (end) of DST suggest potential behavioural adaption from anticipating the change. While Work accidents show limited impact from DST changes, they exhibit a significant decline over the course of the week (Friday 13% lower than Monday), whereas Road accidents exhibit a significant increase (Friday 19% higher than Monday). Our results have implications for both DST implementation and policy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dependence of efficiency of magnetic storm generation on the types of interplanetary drivers.

NASA Astrophysics Data System (ADS)

Yermolaev, Yuri; Nikolaeva, Nadezhda; Lodkina, Irina

2015-04-01

To compare the coupling coefficients between the solar-wind electric field Ey and Dst (and corrected Dst*) index during the magnetic storms generated by different types of interplanetary drivers, we use the Kyoto Dst-index data, the OMNI data of solar wind plasma and magnetic field measurements, and our "Catalog of large scale phenomena during 1976-2000" (published in [1] and presented on websites: ftp://ftp.iki.rssi.ru/pub/omni/). Both indexes at the main phase of magnetic storms are approximated by the linear dependence on the following solar wind parameters: integrated electric field of solar wind (sumEy), solar wind dynamic pressure (Pd), and the level of magnetic field fluctuations (sB), and the fitting coefficients are determined by the technique of least squares. We present the results of the main phase modelling for magnetic storms with Dst<-50 nT induced by 4 types of the solar wind streams: MC (10 events), CIR (41), Sheath (26), Ejecta (45). Our analysis [2, 3] shows that the coefficients of coupling between Dst and Dst* indexes and integral electric field are significantly higher for Sheath (for Dst*and Dst they are -3.4 and -3.3 nT/V m-1 h, respectively) and CIR (-3.0 and -2.8) than for MC (-2.0 and -2.5) and Ejecta (-2.1 and -2.3). Thus we obtained additional confirmation of experimental fact that Sheath and CIR have higher efficiency in generation of magnetic storms than MC and Ejecta. This work was supported by the RFBR, project 13-02-00158a, and by the Program 9 of Presidium of Russian Academy of Sciences. References 1. Yu. I. Yermolaev, N. S. Nikolaeva, I. G. Lodkina, and M. Yu. Yermolaev, Catalog of Large-Scale Solar Wind Phenomena during 1976-2000, Cosmic Research, 2009, Vol. 47, No. 2, pp. 81-94. 2. N.S. Nikolaeva, Yu.I. Yermolaev, I.G. Lodkina, Modeling of Dst-index temporal profile on the main phase of the magnetic storms generated by different types of solar wind, Cosmic Research, 2013, Vol. 51, No. 6, pp. 401-412 3. Nikolaeva N.S., Yermolaev Yu.I., Lodkina I.G., Modeling of corrected Dst-index temporal profile on the main phase of the magnetic storms generated by different types of solar wind, Cosmic Research, 2015, Vol.53, No. 2, 81, DOI: 10.7868/S0023420615020077

Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

PubMed

De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

2008-06-01

The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

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 effects of sedation alone, and thus suitable to investigate the analgesic potential of novel analgesic compounds. © 2018 European Pain Federation - EFIC®.

Alteration in the level of endogenous hypothalamic prostaglandins induced by delta 9-tetrahydrocannabinol in the rat.

PubMed Central

Coupar, I. M.; Taylor, D. A.

1982-01-01

1 Whole brain and regional brain levels of prostaglandin E2 (PGE2)-like material have been determined following administration of delta 9-tetrahydrocannabinol (delta 9 -THC) in rats. 2 Intravenous administration of delta 9-THC 2 mg/kg, resulted in marked behavioural changes and hypothermia. The behavioural changes consisted mainly of catatonia (most apparent at 30 min after administration of delta 9-THC), followed by sedation (most evident at 60 min). Hypothermia was marked from 30 min after administration of delta 9-THC. 3 delta 9-THC did not after the whole brain levels of PGE2-like material 30, 60 or 120 min after administration. 4 delta 9-THC did not alter the levels of PGE2-like material in the medulla oblongata/pons, midbrain, cortex and cerebellum, 30 min after administration. However, there was a significant reduction of PGE2-like material in the hypothalamus, 30 min after delta 9-THC. 5 It is suggested that the delta 9-THC-induced decrease in hypothalamic PGE2-like material may contribute to the hypothermia observed following delta 9-THC administration. PMID:6282371

40 CFR 1065.303 - Summary of required calibration and verifications.

Code of Federal Regulations, 2012 CFR

2012-07-01

... initial installation and after major maintenance. THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers: upon initial installation, within 185 days before...

40 CFR 1065.303 - Summary of required calibration and verifications.

Code of Federal Regulations, 2013 CFR

2013-07-01

... initial installation and after major maintenance. THC FID optimization, and THC FID verification Optimize and determine CH4 response for THC FID analyzers: upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers: upon initial installation, within 185 days before...

Test Plan - Solids Accumulation Scouting Studies

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

Duignan, M. R.; Steeper, T. J.; Steimke, J. L.

This plan documents the highlights of the Solids Accumulations Scouting Studies test; a project, from Washington River Protection Solutions (WRPS), that began on February 1, 2012. During the last 12 weeks considerable progress has been made to design and plan methods that will be used to estimate the concentration and distribution of heavy fissile solids in accumulated solids in the Hanford double-shell tank (DST) 241-AW-105 (AW-105), which is the primary goal of this task. This DST will be one of the several waste feed delivery staging tanks designated to feed the Pretreatment Facility (PTF) of the Waste Treatment and Immobilizationmore » Plant (WTP). Note that over the length of the waste feed delivery mission AW-105 is currently identified as having the most fill empty cycles of any DST feed tanks, which is the reason for modeling this particular tank. At SRNL an existing test facility, the Mixing Demonstration Tank, which will be modified for the present work, will use stainless steel particles in a simulant that represents Hanford waste to perform mock staging tanks transfers that will allow solids to accumulate in the tank heel. The concentration and location of the mock fissile particles will be measured in these scoping studies to produce information that will be used to better plan larger scaled tests. Included in these studies is a secondary goal of developing measurement methods to accomplish the primary goal. These methods will be evaluated for use in the larger scale experiments. Included in this plan are the several pretest activities that will validate the measurement techniques that are currently in various phases of construction. Aspects of each technique, e.g., particle separations, volume determinations, topographical mapping, and core sampling, have been tested in bench-top trials, as discussed herein, but the actual equipment to be employed during the full test will need evaluation after fabrication and integration into the test facility.« less

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 with compounds which share the CYP3A4 pathway such as rifampicin or ketoconazole. NCT01323465.

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity

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

Song, Chenchen; Martínez, Todd J.; SLAC National Accelerator Laboratory, Menlo Park, California 94025

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N{sup 2.6} for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 aremore » less than 0.5 kcal/mol for all systems tested (up to 162 atoms).« less

Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.

PubMed

Malone, Daniel Thomas; Jongejan, Dennis; Taylor, David Alan

2009-08-01

While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1:1 combination for the treatment of conditions such as neuropathic pain. This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social interaction between rat pairs. Treatment with CBD had no significant effect alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in social interaction. A higher dose of THC (10 mg/kg) produced no significant effect on social interaction. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. This data suggests that CBD can reverse social withdrawal induced by low dose THC, but the combination of high dose THC and CBD impairs social interaction, possibly by decreasing locomotor activity.

Gray Matter Loss and Related Functional Connectivity Alterations in A Chinese Family With Benign Adult Familial Myoclonic Epilepsy.

PubMed

Zeng, Ling-Li; Long, Lili; Shen, Hui; Fang, Peng; Song, Yanmin; Zhang, Linlin; Xu, Lin; Gong, Jian; Zhang, Yunci; Zhang, Yong; Xiao, Bo; Hu, Dewen

2015-10-01

Benign adult familial myoclonic epilepsy (BAFME) is a non-progressive monogenic epilepsy syndrome. So far, the structural and functional brain reorganizations in BAFME remain uncharacterized. This study aims to investigate gray matter atrophy and related functional connectivity alterations in patients with BAFME using magnetic resonance imaging (MRI).Eleven BAFME patients from a Chinese pedigree and 15 matched healthy controls were enrolled in the study. Optimized voxel-based morphometric and resting-state functional MRI approaches were performed to measure gray matter atrophy and related functional connectivity, respectively. The Trail-Making Test-part A and part B, Digit Symbol Test (DST), and Verbal Fluency Test (VFT) were carried out to evaluate attention and executive functions.The BAFME patients exhibited significant gray matter loss in the right hippocampus, right temporal pole, left orbitofrontal cortex, and left dorsolateral prefrontal cortex. With these regions selected as seeds, the voxel-wise functional connectivity analysis revealed that the right hippocampus showed significantly enhanced connectivity with the right inferior parietal lobule, bilateral middle cingulate cortex, left precuneus, and left precentral gyrus. Moreover, the BAFME patients showed significant lower scores in DST and VFT tests compared with the healthy controls. The gray matter densities of the right hippocampus, right temporal pole, and left orbitofrontal cortex were significantly positively correlated with the DST scores. In addition, the gray matter density of the right temporal pole was significantly positively correlated with the VFT scores, and the gray matter density of the right hippocampus was significantly negatively correlated with the duration of illness in the patients.The current study demonstrates gray matter loss and related functional connectivity alterations in the BAFME patients, perhaps underlying deficits in attention and executive functions in the BAFME.

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.

Explorative Placebo-Controlled Double-Blind Intervention Study with Low Doses of Inhaled Δ9-Tetrahydrocannabinol and Cannabidiol Reveals No Effect on Sweet Taste Intensity Perception and Liking in Humans.

PubMed

de Bruijn, Suzanne E M; de Graaf, Cees; Witkamp, Renger F; Jager, Gerry

2017-01-01

Introduction: The endocannabinoid system (ECS) plays an important role in food reward. For example, in humans, liking of palatable foods is assumed to be modulated by endocannabinoid activity. Studies in rodents suggest that the ECS also plays a role in sweet taste intensity perception, but it is unknown to what extent this can be extrapolated to humans. Therefore, this study aimed at elucidating whether Δ9-tetrahydrocannabinol (THC) or cannabidiol (CBD) affects sweet taste intensity perception and liking in humans, potentially resulting in alterations in food preferences. Materials and Methods: In a randomized placebo-controlled, double-blind crossover study, 10 healthy males participated in three test sessions that were 2 weeks apart. During the test sessions, participants received THC-rich, CBD-rich, or placebo Cannabis by inhalation divided over two doses (4 + 1 mg THC; 25 + 10 mg CBD). Participants tasted seven chocolate milk-like drinks that differed in sugar concentration and they rated sweet taste intensity and liking of the drinks. They were then asked to rank the seven drinks according to how much they liked the drinks and were offered ad libitum access to their favorite drink. In addition, they completed a computerized food preference task and completed an appetite questionnaire at the start, midway, and end of the test sessions. Results: Inhalation of the Cannabis preparations did not affect sweet taste intensity perception and liking, ranking order, or ad libitum consumption of the favorite drink. In addition, food preferences were not influenced by the interventions. Reported fullness was lower, whereas desire to eat was higher throughout the THC compared to the CBD condition. Conclusions: These results suggest that administration of Cannabis preparations at the low doses tested does not affect sweet taste intensity perception and liking, nor does it influence food preferences in humans.

40 CFR 1065.303 - Summary of required calibration and verifications.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: FID calibrationTHC FID optimization, and THC FID verification Calibrate all FID analyzers: upon initial installation and after major maintenance.Optimize and determine CH4 response for THC FID analyzers: upon initial installation and after major maintenance. Verify CH4 response for THC FID analyzers: upon...

Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers.

PubMed

Mekata, Eiji; Murata, Satoshi; Sonoda, Hiromichi; Shimizu, Tomoharu; Umeda, Tomoko; Shiomi, Hisanori; Naka, Shigeyuki; Yamamoto, Hiroshi; Abe, Hajime; Edamatsu, Takeo; Fujieda, Ayako; Fujioka, Masaki; Wada, Tsutomu; Tani, Tohru

2013-12-01

Protein-bound polysaccharide-K (PSK) enhances the antitumor effect of anticancer drug when used clinically in combination with such drugs. PSK is known to act by immune-mediated mechanisms; however, the relationship between PSK and metabolic enzymes of anticancer drugs is unknown. We used the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) clinically to evaluate the sensitivity of anticancer drugs. In the present study, we modified the CD-DST by adding peripheral blood mononuclear cells (PBMCs) (immuno-CD-DST) and examined the antitumor effect of PSK in combination with anticancer drugs. First, HCT116 human colon cancer cells were cultured with PSK and 5-fluorouracil (5-FU) or 5'-deoxy-5-fluorouridine (5'-DFUR) in the presence or absence of PBMCs, and the antiproliferative effects were compared. In the presence of PBMCs, PSK augmented the inhibitory effects of 5-FU and 5'-DFUR on HCT116 cell proliferation. Next, using human gastric cancer and colon cancer cell lines, the effects of PSK on mRNA expression of various metabolic enzymes of fluoropyrimidines: dihydropyrimidine dehydrogenase (DPD), thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl transferase, were examined by real-time PCR. PSK significantly enhanced DPD mRNA expression in all of the cancer cell lines tested, but not those of the other enzymes. Addition of IFN-α and TRAIL, cytokines known to inhibit DPD expression, to the cultures reduced DPD mRNA expression in the cancer cells. When PBMC samples collected from healthy volunteers were cultured with PSK, IFN-α mRNA expression increased in 3 of the 5 PBMC samples, while TRAIL mRNA expression was unchanged. The present results propose the possibility that PSK induces PBMCs to express IFN-α which inhibits DPD expression, and consequently augments the antitumor effect of 5-FU or 5'-DFUR. Immuno-CD-DST is useful for evaluating drugs with immunological mechanisms of action.

A Multilaboratory, Multicountry Study To Determine Bedaquiline MIC Quality Control Ranges for Phenotypic Drug Susceptibility Testing

PubMed Central

Cirillo, Daniela M.; Hoffner, Sven; Ismail, Nazir A.; Kaur, Devinder; Lounis, Nacer; Metchock, Beverly; Pfyffer, Gaby E.; Venter, Amour

2016-01-01

The aim of this study was to establish standardized drug susceptibility testing (DST) methodologies and reference MIC quality control (QC) ranges for bedaquiline, a diarylquinoline antimycobacterial, used in the treatment of adults with multidrug-resistant tuberculosis. Two tier-2 QC reproducibility studies of bedaquiline DST were conducted in eight laboratories using Clinical Laboratory and Standards Institute (CLSI) guidelines. Agar dilution and broth microdilution methods were evaluated. Mycobacterium tuberculosis H37Rv was used as the QC reference strain. Bedaquiline MIC frequency, mode, and geometric mean were calculated. When resulting data occurred outside predefined CLSI criteria, the entire laboratory data set was excluded. For the agar dilution MIC, a 4-dilution QC range (0.015 to 0.12 μg/ml) centered around the geometric mean included 95.8% (7H10 agar dilution; 204/213 observations with one data set excluded) or 95.9% (7H11 agar dilution; 232/242) of bedaquiline MICs. For the 7H9 broth microdilution MIC, a 3-dilution QC range (0.015 to 0.06 μg/ml) centered around the mode included 98.1% (207/211, with one data set excluded) of bedaquiline MICs. Microbiological equivalence was demonstrated for bedaquiline MICs determined using 7H10 agar and 7H11 agar but not for bedaquiline MICs determined using 7H9 broth and 7H10 agar or 7H9 broth and 7H11 agar. Bedaquiline DST methodologies and MIC QC ranges against the H37Rv M. tuberculosis reference strain have been established: 0.015 to 0.12 μg/ml for the 7H10 and 7H11 agar dilution MICs and 0.015 to 0.06 μg/ml for the 7H9 broth microdilution MIC. These methodologies and QC ranges will be submitted to CLSI and EUCAST to inform future research and provide guidance for routine clinical bedaquiline DST in laboratories worldwide. PMID:27654337

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/10.1111/bph.2011.163.issue-7 PMID:21699509

Suppression of human macrophage function in vitro by delta 9-tetrahydrocannabinol.

PubMed

Specter, S; Lancz, G; Goodfellow, D

1991-11-01

The ability of macrophages to function in the presence of delta 9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was evaluated. THC added to macrophage cultures prepared from human peripheral blood inhibited macrophage spreading and phagocytosis of yeast. The effects of THC were concentration dependent, with inhibitory effects observed from 10 to 1 micrograms/ml or lower. These results suggest that macrophages are more sensitive to THC than are lymphocytes because macrophage functions were inhibited by THC at concentrations that did not affect lymphocyte function. Thus, inhibition of lymphocyte function(s) by THC could be attributed to a direct effect of the drug on macrophages which indirectly results in lowered lymphoid cell activity.

Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis.

PubMed

Morgan, Celia J A; Curran, H Valerie

2008-04-01

Cannabis contains various cannabinoids, two of which have almost opposing actions: Delta9-tetrahydrocannabinol (Delta9-THC) is psychotomimetic, whereas cannabidiol (CBD) has antipsychotic effects. Hair samples were analysed to examine levels of Delta9-THC and CBD in 140 individuals. Three clear groups emerged: ;THC only', ;THC+CBD' and those with no cannabinoid in hair. The THC only group showed higher levels of positive schizophrenia-like symptoms compared with the no cannabinoid and THC+CBD groups, and higher levels of delusions compared with the no cannabinoid group. This provides evidence of the divergent properties of cannabinoids and has important implications for research into the link between cannabis use and psychosis.

Leptospirosis Outbreak following Severe Flooding: A Rapid Assessment and Mass Prophylaxis Campaign; Guyana, January–February 2005

PubMed Central

Dechet, Amy M.; Parsons, Michele; Rambaran, Madan; Mohamed-Rambaran, Pheona; Florendo-Cumbermack, Anita; Persaud, Shamdeo; Baboolal, Shirematee; Ari, Mary D.; Shadomy, Sean V.; Zaki, Sherif R.; Paddock, Christopher D.; Clark, Thomas A.; Harris, Lazenia; Lyon, Douglas; Mintz, Eric D.

2012-01-01

Background Leptospirosis is a zoonosis usually transmitted through contact with water or soil contaminated with urine from infected animals. Severe flooding can put individuals at greater risk for contracting leptospirosis in endemic areas. Rapid testing for the disease and large-scale interventions are necessary to identify and control infection. We describe a leptospirosis outbreak following severe flooding and a mass chemoprophylaxis campaign in Guyana. Methodology/Principal Findings From January–March 2005, we collected data on suspected leptospirosis hospitalizations and deaths. Laboratory testing included anti-leptospiral dot enzyme immunoassay (DST), immunohistochemistry (IHC) staining, and microscopic agglutination testing (MAT). DST testing was conducted for 105 (44%) of 236 patients; 52 (50%) tested positive. Four (57%) paired serum samples tested by MAT were confirmed leptospirosis. Of 34 total deaths attributed to leptospirosis, postmortem samples from 10 (83%) of 12 patients were positive by IHC. Of 201 patients interviewed, 89% reported direct contact with flood waters. A 3-week doxycycline chemoprophylaxis campaign reached over 280,000 people. Conclusions A confirmed leptospirosis outbreak in Guyana occurred after severe flooding, resulting in a massive chemoprophylaxis campaign to try to limit morbidity and mortality. PMID:22808049

Lattice dynamics and lattice thermal conductivity of thorium dicarbide

NASA Astrophysics Data System (ADS)

Liao, Zongmeng; Huai, Ping; Qiu, Wujie; Ke, Xuezhi; Zhang, Wenqing; Zhu, Zhiyuan

2014-11-01

The elastic and thermodynamic properties of ThC2 with a monoclinic symmetry have been studied by means of density functional theory and direct force-constant method. The calculated properties including the thermal expansion, the heat capacity and the elastic constants are in a good agreement with experiment. Our results show that the vibrational property of the C2 dimer in ThC2 is similar to that of a free standing C2 dimer. This indicates that the C2 dimer in ThC2 is not strongly bonded to Th atoms. The lattice thermal conductivity for ThC2 was calculated by means of the Debye-Callaway model. As a comparison, the conductivity of ThC was also calculated. Our results show that the ThC and ThC2 contributions of the lattice thermal conductivity to the total conductivity are 29% and 17%, respectively.

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…

40 CFR Table 7 to Subpart Sssss of... - Continuous Compliance with Emission Limits

Code of Federal Regulations, 2010 CFR

2010-07-01

... average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen; OR the average THC... other than a thermal or catalytic oxidizer The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen; OR the average THC performance reduction must equal or exceed 95 percent...

40 CFR Table 7 to Subpart Sssss of... - Continuous Compliance with Emission Limits

Code of Federal Regulations, 2012 CFR

2012-07-01

... average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen; OR the average THC... other than a thermal or catalytic oxidizer The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen; OR the average THC performance reduction must equal or exceed 95 percent...

32 CFR 161.16 - Benefits for transitional health care members and dependents.

Code of Federal Regulations, 2014 CFR

2014-07-01

... members and dependents. This section shows the benefits for THC members and their eligible dependents. THC... Defense Authorization Act of for Fiscal Year 2005” made the THC program permanent and made the medical... years' commissary and exchange benefits to THC members. Section 734 of Public Law 110-417, “National...

40 CFR Table 3 to Subpart Ppppp of... - Requirements for Initial Compliance Demonstrations

Code of Federal Regulations, 2011 CFR

2011-07-01

... with . . . You must . . . Using . . . According to the following requirements . . . 1. The CO or THC outlet concentration emission limitation a. Demonstrate CO or THC emissions are 20 ppmvd or less i. EPA... CFR part 60 for THC measurement; or You must demonstrate that the outlet concentration of CO or THC...

40 CFR Table 3 to Subpart Ppppp of... - Requirements for Initial Compliance Demonstrations

Code of Federal Regulations, 2010 CFR

2010-07-01

... with . . . You must . . . Using . . . According to the following requirements . . . 1. The CO or THC outlet concentration emission limitation a. Demonstrate CO or THC emissions are 20 ppmvd or less i. EPA... CFR part 60 for THC measurement; or You must demonstrate that the outlet concentration of CO or THC...

40 CFR Table 7 to Subpart Sssss of... - Continuous Compliance with Emission Limits

Code of Federal Regulations, 2011 CFR

2011-07-01

... average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen; OR the average THC... other than a thermal or catalytic oxidizer The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen; OR the average THC performance reduction must equal or exceed 95 percent...