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Abused Drugs (abused + drug)
Selected AbstractsCombined Dextromethorphan and Chlorpheniramine Intoxication in Impaired DriversJOURNAL OF FORENSIC SCIENCES, Issue 5 2009Barry K. Logan Ph.D., D-ABFT Abstract:, Dextromethorphan is a nonprescription antitussive which has been gaining in popularity as an abused drug, because of the hallucinogenic, dissociative, and intoxicating effects it produces at high doses. This report describes a series of eight drivers arrested for driving under the influence of the combined effects of dextromethorphan and chlorpheniramine, and a further four drivers under the influence of dextromethorphan alone. In the combined dextromethorphan/chlorpheniramine cases, blood dextromethorphan concentrations ranged from 150 to 1220 ng/mL (n = 8; mean 676 ng/mL, median 670 ng/mL), and chlorpheniramine concentrations ranged from 70 to 270 ng/mL (n = 8; mean 200 ng/mL, median 180 ng/mL). The four cases without chlorpheniramine present had blood dextromethorphan concentrations between 190 and 1000 ng/mL (mean 570 ng/mL, median 545 ng/mL). Some drivers had therapeutic concentrations of other drugs present. Drivers generally displayed symptoms of central nervous system (CNS) depressant intoxication, and there was gross evidence of impairment in their driving, including weaving, leaving the lane of travel, failing to obey traffic signals, and involvement in collisions. Drug Recognition Expert opinions confirmed that the subjects were under the influence of a drug in the CNS-depressant category. [source] CLINICAL STUDY: Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentinADDICTION BIOLOGY, Issue 1 2009Barbara J. Mason ABSTRACT There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs. [source] Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in ratsJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Marcello Solinas Abstract Although endogenous cannabinoid systems have been implicated in the modulation of the rewarding effects of abused drugs and food, little is known about the direct effects of endogenous ligands for cannabinoid receptors on brain reward processes. Here we show for the first time that the intravenous administration of anandamide, an endogenous ligand for cannabinoid receptors, and its longer-lasting synthetic analog methanandamide, increase the extracellular dopamine levels in the nucleus accumbens shell of awake, freely moving rats, an effect characteristic of most drugs abused by humans. Anandamide produced two distinctly different effects on dopamine levels: (1) a rapid, transient increase that was blocked by the cannabinoid CB1 receptor antagonist rimonabant, but not by the vanilloid VR1 receptor antagonist capsazepine, and was magnified and prolonged by the fatty acid amide hydrolase (FAAH) enzyme inhibitor, URB597; (2) a smaller delayed and long-lasting increase, not sensitive to CB1, VR1 or FAAH blockade. Both effects were blocked by infusing either tetrodotoxin (TTX, 1 µm) or calcium-free Ringer's solution through the microdialysis probe, demonstrating that they were dependent on the physiologic activation of dopaminergic neurotransmission. Thus, these results indicate that anandamide, through the activation of the mesolimbic dopaminergic system, participates in the signaling of brain reward processes. [source] Altered gene expression in frontal cortex and midbrain of 3,4-methylenedioxymethamphetamine (MDMA) treated mice: Differential regulation of GABA transporter subtypesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Weiping Peng Abstract Changes in gene expression were examined in the brain of mice treated with a drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, also called Ecstasy). Frontal cortex and midbrain mRNA, analyzed by differential display polymerase chain reaction (DD-PCR) method, showed an altered expression of several cDNAs, 11 of which were isolated, cloned and sequenced. The sequence of one MDMA-induced mRNA corresponds (99.3%) to the mouse ,-amino butyric acid (GABA) transporter 1 (mGAT1). The established involvement of GABA neurotransmission in the activity of several abused drugs prompted us to focus herein on MDMA effect on the GABA transporter gene family. Semi-quantitative PCR analysis with primers selective to the reported mGAT1 sequence confirmed that MDMA treatment increased mGAT1 expression. Time-course study of the expression of the three GABA transporter subtypes showed that MDMA induced a differential temporal activation of mGAT1 and mGAT4, but had no effect on mGAT2. Quantitative real-time PCR further proved the increased expression of mGAT1 and mGAT4 upon MDMA treatment. Western immunoblotting with anti-GAT1 antibodies showed that MDMA also increased GAT1 protein levels, suggesting that neurotransmission of GABA was altered. MDMA effect was also verified in serotonin transporter knockout (,/,) mice that are insensitive behaviorally to MDMA; the drug did not increase GAT1 protein level in these mutants. In mice, tiagabine and NO-711, inhibitors of GABA transporters, restrained MDMA-induced acute toxicity and death. These results should facilitate novel approaches to prevent deleterious effects, including fatality, induced by MDMA and similar abused psychostimulants. © 2003 Wiley-Liss, Inc. [source] Rapid and sensitive determination of strychnine and brucine in human urine by capillary electrophoresis with field-amplified sample stackingBIOMEDICAL CHROMATOGRAPHY, Issue 2 2010Junmei Li Abstract A simple, rapid, sensitive and low-cost method using capillary electrophoresis (CE) coupled with field-amplified sample stacking (FASS) has been developed and validated for the simultaneous determination of strychnine and brucine residues in human urine. Before sample loading, a water plug (3.5 kPa, 3,s) was injected to contain sample cations and to permit FASS. Electrokinetic injection at a voltage (20 kV, 25,s) was then used to introduce cations. Separation was performed using 20,mM acetate buffer (pH 3.8) with an applied voltage of 20 kV. The calibration curves were linear over a range of 8.00,2.56 , 102,ng/mL (r = 0.9995) for strychnine and 10.0,3.20 × 102,ng/mL (r = 0.9999) for brucine. Extraction recoveries in urine were greater than 79.6 and 82.8% for strychnine and brucine, respectively, with an RSD of less than 4.9%. The detection limits (signal-to-noise ratio 3) for strychnine and brucine were 2.00 and 2.50,ng/mL, respectively. A urine sample from one healthy female volunteer (26 years old, 50,kg) was pretreated and analyzed. Strychnine and brucine levels in urine could be detected 24,h after administration. On these grounds, this method was feasible for application to preliminary screening of trace levels of abused drugs for both doping control and forensic analysis. Copyright © 2009 John Wiley & Sons, Ltd. [source] The endocannabinoid system in brain reward processesBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008M Solinas Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammals to favour fitness and survival. For decades, endogenous dopaminergic and opioid systems have been considered the most important systems in mediating brain reward processes. Recent evidence suggests that the endogenous cannabinoid (endocannabinoid) system also has an important role in signalling of rewarding events. First, CB1 receptors are found in brain areas involved in reward processes, such as the dopaminergic mesolimbic system. Second, activation of CB1 receptors by plant-derived, synthetic or endogenous CB1 receptor agonists stimulates dopaminergic neurotransmission, produces rewarding effects and increases rewarding effects of abused drugs and food. Third, pharmacological or genetic blockade of CB1 receptors prevents activation of dopaminergic neurotransmission by several addictive drugs and reduces rewarding effects of food and these drugs. Fourth, brain levels of the endocannabinoids anandamide and 2-arachidonoylglycerol are altered by activation of reward processes. However, the intrinsic activity of the endocannabinoid system does not appear to play a facilitatory role in brain stimulation reward and some evidence suggests it may even oppose it. The influence of the endocannabinoid system on brain reward processes may depend on the degree of activation of the different brain areas involved and might represent a mechanism for fine-tuning dopaminergic activity. Although involvement of the various components of the endocannabinoid system may differ depending on the type of rewarding event investigated, this system appears to play a major role in modulating reward processes. British Journal of Pharmacology (2008) 154, 369,383; doi:10.1038/bjp.2008.130; published online 14 April 2008 [source] | |||||||||||||