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lol schoubi...
Tenez, pour vous occuper, je vous ai tiré les derniers articles médicaux sur la question. Ce ne sont que les 'abstracts' mais si vous êtes intéressés, vous aurez les références...
Citation: 1: Neuropharmacology. 2004;47 Suppl 1:345-58.
Cannabinoid physiology and pharmacology: 30 years of progress.
Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ.
Neuroscience of Drug Abuse Research Program, Julius L. Chambers
Biomedical/Biotechnology Research Institute at North Carolina Central
University, Durham, NC 27707, USA.
Delta(9)-Tetrahydrocannabinol from Cannabis sativa is mimicked by cannabimimetic analogs such as CP55940 and WIN55212-2, and antagonized by rimonabant and SR144528, through G-protein-coupled receptors, CB(1) in the brain, and CB(2) in the immune system. Eicosanoids anandamide and 2-arachidonoylglycerol are the "endocannabinoid" agonists for these receptors. CB(1) receptors are abundant in basal ganglia, hippocampus and cerebellum, and their functional activity can be mapped during behaviors using cerebral metabolism as the neuroimaging tool. CB(1) receptors couple to G(i/o) to inhibit cAMP production, decrease Ca(2+) conductance, increase K(+) conductance, and increase mitogen-activated protein
kinase activity. Functional activation of G-proteins can be imaged by [35S]GTPgammaS autoradiography. Post-synaptically generated endocannabinoids form the basis of a retrograde signaling mechanism referred to as depolarization-induced suppression of inhibition (DSI) or excitation (DSE). Under circumstances of sufficient intracellular Ca(2+) (e.g., burst activity in seizures), synthesis of endocannabinoids releases a diffusible retrograde
messenger to stimulate presynaptic CB(1) receptors. This results in suppression of gamma-aminobutyric acid (GABA) release, thereby relieving the post-synaptic inhibition. Tolerance develops as neurons adjust both receptor number and cellular signal transduction to the chronic administration of cannabinoid drugs. Future therapeutic drug design can progress based upon our current understanding of the physiology and pharmacology of CB(1), CB(2) and related receptors. One very important role for CB(1) antagonists will be in the treatment of craving in the disease of substance abuse.
PMID: 15464149 [PubMed - in process] |
Citation: 2: Forensic Sci Int. 2004 Oct 29;145(2-3):143-7.
Cannabinoids in hair: strategy to prove marijuana/hashish consumption.
Uhl M, Sachs H.
Bayerisches Landeskriminalamt, Maillingerstrasse 15, 80636 Munchen, Germany.
Delta(9)-Tetrahydrocannabinol (THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THCA) are equally used to indicate consumption of cannabis (hashish and marijuana). Publications of the early 90's demonstrate the possibilities of determining THC, cannabinol (CBN), and cannabidiol (CBD). All these substances are present in cannabis smoke and can be incorporated into the hair only by contamination. Generally, washing procedures should prevent false positive results, but finally it cannot be excluded that traces of THC may be found in hair after mere passive cannabis smoke exposure. Three authentic cases illustrate the problems originating in the exclusive determination of THC/CBN. The first example is the case of a couple living together in an apartment. Both persons' hair samples had been taken and gave positive results for THC and CBN. The male subject admitted smoking cannabis several times per day, but the female mate denied any consumption. Examination of the hair for THCA showed a high level (>6.6pg/mg) in the sample of the male person and negative results (LOQ 0.1pg/mg) in the sample of his mate. The second case hair is of a self admitted cannabis user's hair and was tested first by an immunoassay and GC/MS with a negative result. Nevertheless, the THCA concentration quantified in his sample was 2.7pg/mg hair. The third hair sample is of a 2-year-old child that was tested positive for cannabis by using an immunochemical test. No THC and CBN were detectable by GC/MS, however, trace amounts of THCA using GC/MS/MS. A comparative study of hair samples (screening for cannabinoids using ELISA test, THC determination by GC/MS, THCA by GC/MS/MS) showed that only 26 segments of 66 were positive for both THC and THCA. Thirteen were negative for THC and positive for THCA, and six were positive for THC but negative for THCA. The cases were selected by an ELISA test or re-examined when the blood/urine results or the statement of the accused did not match with a THC outcome. The most appropriate strategy to prove cannabis consumption is immunochemical initial test followed by a GC/MS/MS confirmation of THCA.
PMID: 15451086 [PubMed - in process] |
Citation: 3: Forensic Sci Int. 2004 Oct 29;145(2-3):123-30.
Determination of bromazepam, clonazepam and metabolites after a single intake in
urine and hair by LC-MS/MS; Application to forensic cases of drug facilitated
crimes.
Cheze M, Villain M, Pepin G.
Laboratory of Toxicology, TOXLAB, 7 rue Jacques Cartier, 75018 Paris, France.
The number of reports on drug facilitated crimes is increasing these last years. Apart from ethanol and cannabis, benzodiazepines (BZD) and analogs are the most common drugs reported to be used probably due to their amnesic and sedative properties. We have developed a rapid and sensitive method using LC-MS/MS triple stage quadrupole (TSQ) for the determination of single exposure to bromazepam (Lexomil((R)), 6mg) and clonazepam (Rivotril((R)), 2mg) in urine and hair of healthy volunteers. Chromatography was carried out on a Uptisphere ODB 5microm, 2.1mm x 150mm column (Interchim) with a gradient of acetonitrile and formate 2mM buffer, pH 3. Urine was extracted with Toxitube A((R)) (Varian) and allowed the detection of bromazepam, 3-hydroxy-bromazepam, clonazepam and 7-Aminoclonazepam for more than 6 days. Head hair, collected 1 month after the exposure, was treated by incubation with Soerensen buffer pH 7.6, followed by liquid-liquid extraction with dichloromethane for common BZD. A specific pre-treatment for amino-BZD, with an incubation of 15min at 95 degrees C in 0.1N NaOH before liquid-liquid extraction with dichloromethane, gave better recoveries and repeatability. After single exposure, bromazepam was present in powdered hair at 28pg/mg and 7-Aminoclonazepam at 22pg/mg in the first 1-cm segment, while no clonazepam was detectable. This method was applied in two forensic cases. It allowed us to determine bromazepam in urine 3 days after the alleged offense and in cut head hair at a concentration of 6.7pg/mg only in the 2-cm proximal segment. The other case showed the presence of clonazepam and 7-Aminoclonazepam in urine a few hours after the offense and the presence of 7-Aminoclonazepam at about 3.2pg/mg in axillary hair 4 months later.
PMID: 15451083 [PubMed - in process] |
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