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- National study of illicit drug use in Slovakia based on wastewater analysis. [JOURNAL ARTICLE]
- Sci Total Environ 2014 Jul 18.:158-165.
The aim of this study was to analyze illicit drugs and their metabolites in wastewater from eight selected wastewater treatment plants (WWTPs) in Slovakia. The effect of two of the biggest music festivals in Slovakia on illicit drugs in wastewater was also investigated. Urinary bio-markers of amphetamine, methamphetamine, cocaine, cannabis and ecstasy use were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We then compared our results with data obtained in other parts of Europe and the world. This study demonstrates that Slovakia has one of highest methamphetamine consumption rates in Europe. Within Slovakia, the highest level of methamphetamine consumption was found in Petržalka, where the mean specific load of this drug in sewage was 169mg/day/1000 inhabitants; the next highest loads were detected in Piešťany (128mg/day/1000 inhabitants) and Bratislava (124mg/day/1000 inhabitants). Amphetamine, ecstasy and cannabis consumption in our study were comparable to that found in other European cities, whereas cocaine consumption was lower. We also analyzed the pattern of drug consumption over the course of a week. The load of the cocaine metabolite benzoylecgonine in wastewater increased during the weekend. The use of this drug was most common in the capital of Slovakia. Increased consumption was also found during a folk festival in Piešťany. The ecstasy load in wastewater from larger cities also significantly increased over the weekend. An increase of drug consumption was also detected during a music festival in Trenčín, especially for ecstasy. The specific load of ecstasy during this festival increased from 3mg/day/1000 inhabitants to 29mg/day/1000 inhabitants. The possible influence of music styles on the consumption of certain drugs was also observed. During a folk festival, methamphetamine and cocaine were more commonly used.
- Involvement of the brain Renin-Angiotensin System (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol. [JOURNAL ARTICLE]
- Behav Brain Res 2014 Jul 18.
A single or repeated exposure to psychostimulants induces long-lasting neuroadaptative changes. Different neurotransmitter systems are involved in these responses including the neuropeptide angiotensin II. Our study tested the hypothesis that the neuroadaptative changes induced by amphetamine produce alterations in brain RAS components that are involved in the expression of the locomotor sensitization to the psychostimulant drug. Wistar male rats, pretreated with amphetamine were used 7 or 21 days later to study AT1 receptors by immunohistochemistry and western blot and also angiotensinogen mRNA and protein in caudate putamen and nucleus accumbens. A second group of animals was used to explore the possible role of Ang II AT1 receptors in the expression of behavioral sensitization. In these animals treated in the same way, bearing intra-cerebral cannula, the locomotor activity was tested 21 days later, after an amphetamine challenge injection and the animals received an AT1 blocker, losartan, or saline 5min before the amphetamine challenge. An increase of AT1 receptor density induced by amphetamine was found in both studied areas and a decrease in angiotensinogen mRNA and protein only in CPu at 21 days after treatment; meanwhile, no changes were established in NAcc. Finally, the increased locomotor activity induced by amphetamine challenge was blunted by losartan administration in CPu. No differences were detected in the behavioral sensitization when the AT1 blocker was injected in NAcc. Our results support the hypothesis of a key role of brain RAS in the neuroadaptative changes induced by amphetamine.
- Influence of stimulant and non-stimulant drug treatment on driving performance in patients with attention deficit hyperactivity disorder: A systematic review. [REVIEW]
- Eur Neuropsychopharmacol 2014 Jun 28.
Adults with Attention Deficit Hyperactivity Disorder (ADHD), especially teenagers and young adults, show important car driving impairments, including risky driving, accidents, fines and suspension of driver׳s license. We systematically reviewed the efficacy of stimulant and non-stimulant drugs on driving performance of ADHD patients. We searched several databases for randomized controlled trials (RCTs) published through March, 2013. Fifteen RCTs (the majority with crossover design) evaluated methylphenidate (MPH) immediate-release (MPH-IR), MPH osmotic-controlled oral system (MPH-OROS), MPH transdermal system (MTS), extended-release mixed amphetamine salts (MAS-XR); atomoxetine (ATX) and lisdexamfetamine (LDX). Methods varied widely; including simulators and/or cars and different courses and scenarios. Various outcomes of driving performance, including a 'composite' or 'overall' driving score were considered. In general, stimulants improved driving performance in ADHD patients (either in RCTs conducted in simulators and/or cars). MPH-OROS improved driving performance compared with MAS-XR, placebo, or no-drug conditions. Although MPH-OROS and MPH-IR produced similar improvements during the day, MPH-IR lost its efficacy in the evening. MAS-XR also improved driving performance, but worsened driving performance in the evening. MTS (one study) showed a positive effect, but drug compliance varied widely across patients. LDX had positive effect on driving (two studies with the same sample). Studies with ATX report conflicting results. Improvement was more consistent in teenagers and young adults. In general, treatment with psychostimulants or ATX in therapeutic dosages had no negative impact on driving performance of ADHD patients. To conclude, treatment with stimulants in therapeutic doses improves driving performance in ADHD patients, especially teenagers and young adults.
- RECENT Cocaine USE is a SIGNIFICANT risk factor for sudden cardiovascular death in 15-49 years old SUBJECTS. A forensic case-control study. [JOURNAL ARTICLE]
- Addiction 2014 Jul 21.
The aims of the present study were: (i) to evaluate the prevalence of recent use of cocaine in adolescents and young adults who died by sudden cardiovascular death (SCVD); (ii) to assess if recent use of cocaine was associated with an increased risk of SCVD; and (iii) to determinate the demographic, clinic-pathological and toxicological characteristics of SCVD related to recent cocaine use.This was a case-control autopsy-based observational retrospective study.Cases were all SCVD in persons between 15 and 49 years old during the period ranging from 1 January 2003 to 31 December 2009 with autopsy performed in Biscay, Spain. Medicolegal sudden deaths not due to cardiovascular diseases (SnoCVD) were used as control group. In all deaths a complete autopsy and toxicological and histopathological studies were carried out. Recent use of cocaine was considered when cocaine and/or benzoylecgonine were detected in blood.The risk for SCVD according to demographic variables (sex and age), cardiovascular risk factors (obesity, hypertension, diabetes and smoking) and toxicological variables (opioids, benzodiazepines, amphetamines, cannabis and alcohol) was analyzed using 3 logistic regression models. We also estimated the prevalence of recent cocaine use in the general population aged 15-49 years based on the projection of population surveys.Recent use of cocaine was significantly higher in the SCVD group (27 of 311 subjects, 9%) than in the SnoCVD group (3 of 126 subjects, 2%). In a full logistic regression controlling for all recorded covariates, the main risk factor for SCVD was the recent use of cocaine (odds ratio 4.10; 95% confidence interval 1.12 to 15). Compared with estimated data in the general population, the prevalence of recent use of cocaine was 13 to 58 times higher in people with SCVD.Recent use of cocaine is significantly associated with an increased risk for sudden cardiovascular death in people 15-49 years old.
- Commentary on Ort et al. (2014): What next to deliver on the promise of large scale sewage-based drug epidemiology? [Journal Article]
- Addiction 2014 Aug; 109(8):1353-4.
- Simultaneous Analysis of Amphetamine-type Stimulants in Plasma by Solid-phase Microextraction and Gas Chromatography-Mass Spectrometry. [JOURNAL ARTICLE]
- J Anal Toxicol 2014 Jul 19.
Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN). The use of ATS is mostly linked to diverted prescription stimulants and this misuse is widely associated with (ab)use by drivers. A validated method was developed for the simultaneous analysis of amphetamine (AMP), DIE and FEN in plasma samples employing direct immersion-solid-phase microextraction, and gas chromatographic/mass spectrometric analysis. Trichloroacetic acid 10% was used for plasma deproteinization. In situ derivatization with propylchloroformate was employed. The linear range of the method covered from 5.0 to 100 ng/mL. The detection limits were 1.0 (AMP), 1.5 (DIE) and 2.0 ng/mL (FEN). The accuracy assessment of the control samples was within 85.58-108.33% of the target plasma concentrations. Recoveries ranged from 46.35 to 84.46% and precision was <15% of the value of relative standard deviation. This method is appropriate for screening and confirmation in plasma forensic toxicology analyses of these basic drugs.
- Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons. [JOURNAL ARTICLE]
- Neuron 2014 Jul 16; 83(2):404-416.
Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization and its action on excitatory responses. These data indicate that the internalization of EAAT3 triggered by amphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.
- Stereoisomeric profiling of drugs of abuse and pharmaceuticals in wastewaters of Valencia (Spain). [JOURNAL ARTICLE]
- Sci Total Environ 2014 Jul 12.:49-57.
The enantiomeric and diastereomeric profiling of chiral pharmaceuticals (ephedrine, norephedrine, atenolol and venlafaxine) and illicit drugs (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)) was undertaken over a period of fourteen consecutive days in three wastewater treatment plants (WWTPs) in the city of Valencia, Spain. Degradation efficiency of WWTPs was found to be compound and enantiomer dependent. Selective enantiomer enrichment was observed for several target analytes. Amphetamine and MDMA were enriched with R(-)-enantiomers. 1S,2S(+)-pseudoephedrine was found to be more readily degradable during activated sludge treatment than its diastereomer 1R,2S(-)-ephedrine. Atenolol underwent enrichment with either S(-)- or R(+)-enantiomer in different WWTPs. This unexpected enantiomeric variation in the stereoselective degradation of atenolol could be attributed to different processes utilized during activated sludge treatment. The application of (enantiomeric) profiling of wastewater revealed usage patterns of chiral drugs in the Valencia region.
- Illicit drug abuse affects periodontal health status. [Journal Article]
- Saudi Med J 2014 Jul; 35(7):724-8.
To determine periodontal health status among drug addicts in Jeddah, Kingdom of Saudi Arabia.Drug addiction recovery patients were recruited from Al-Amal Rehabilitation Hospital, Jeddah, Kingdom of Saudi Arabia between October and December 2012. A questionnaire was used to determine socio-demographic data, oral hygiene measures, and previous drug abuse. Full periodontal charting was carried out including probing depth, recession, attachment loss, bleeding on probing, and plaque index.A total of 57 male patients participated in the study. Cannabis was the drug of choice of most (66.7%) of the subjects, followed by amphetamines (52.6%), alcohol (43.9%), heroin (35.1%), and 8.8% reported using cocaine. All participants had some form of periodontitis with moderate chronic periodontitis affecting 60% of the sample, while mild periodontitis affected 29.1%, and severe periodontitis affected 10.9% of the sample. Cocaine and heroin users showed higher mean clinical attachment loss compared with non-users (p<0.05). Pocket depths of 5-6 mm were found in more than half of the sample. Cocaine users had the highest percentage (80%) of pocket depths that ranged from 5-6 mm.Illicit drug use, especially heroin and cocaine, is associated with more severe forms of periodontitis.
- [Topiramate in substance-related and addictive disorders.] [JOURNAL ARTICLE]
- Presse Med 2014 Jul 11.
Drug treatments used in substance use disorders are not effective in all patients.To assess the effectiveness of topiramate use in the treatment of substance use disorders.Medline database from January 1966 to December 2013, Cochrane database and clinicaltrials.gov.We used keywords topiramate, addiction, substance abuse, alcohol, tobacco, nicotine, cocaine, methamphetamine, opiate, heroin, benzodiazepine, cannabis, bulimia nervosa, binge eating disorder, gambling. All clinical trials were included. Animal trials, laboratory tests, reviews, answers to writers, case-reports, case series and publications unrelated to the topic were excluded. Twenty-eight articles investigating the efficacy of topiramate in substance use were included.In alcohol-related disorder, several trials and a meta-analysis showed a reduction of days of consumption. In a single-center trial on tobacco-related disorder, topiramate was not found effective in reducing the carbon monoxide expired. In cocaine-related disorder, one single-center trial showed a reduction of days of consumption and two single-center trials have found a trend in favour of topiramate. In alcohol and cocaine co-dependency, a single-center trial found a trend in favour of topiramate. In methamphetamine-related disorder, a multicenter trial found a trend in favour of topiramate. In bulimia nervosa, two single-center trials showed a reduction in binge eating and compensatory behaviours. In binge eating disorder, several trials showed a reduction of binge eating and weight. In gambling, one single-center trial did not show any significant results. There were no randomized controlled trials found in opioid-related disorder, benzodiazepines-related disorder, and cannabis-related disorder.Definition of abstinence and methods to assess the efficacy of topiramate differed between trials. The methodological quality of included trials was variable, especially with no double-blind procedure in eight trials.Topiramate showed interest mainly in alcoholism, binge eating disorder and bulimia nervosa. No definitive conclusions can be reached for other substance use disorders such as nicotine dependence, cocaine dependence, amphetamine dependence or cannabis dependence and for gambling.