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- Indirect Chiral Separation of New Recreational Drugs by Gas Chromatography-Mass Spectrometry Using Trifluoroacetyl-L-Prolyl Chloride as Chiral Derivatization Reagent. [JOURNAL ARTICLE]
- Chirality 2014 Nov 22.
New recreational drugs such as amphetamine-, cathinone, and benzofury derivatives gained high popularity on the drug market in recent years. They can be purchased via the Internet from different providers and online portals. Most of these compounds are chiral, which makes the development of chiral separation methods necessary. Besides this, it is useful to find out if the compounds were sold as racemic mixtures. Also, it is important to check whether the new psychoactive compounds contain further ingredients or impurities. The aim of this research was the continuation of the application of a method for indirect chiral separation of 24 new psychoactive compounds recently purchased via the Internet. After derivatization with the chiral derivatization reagent trifluoroacetyl-L-prolyl chloride, chromatographic separation of diastereomers was achieved using a 30 m HP5-MS capillary column. As carrier gas, helium was used with a constant flow of 1.0 ml/min. Three different column temperature programs were tested. Under optimum conditions 13 out of 24 compounds were successfully resolved into their enantiomers obtaining Rs values up to 7.0. The use of a single quadrupole mass spectrometer as the detector allowed the identification of the compounds in multicomponent samples. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
- A review of substance abuse research in malaysia. [Journal Article]
- Med J Malaysia 2014 Aug.:55-8.
This is a review of research done in the area of substance abuse in Malaysia. There were 109 articles related to substance abuse found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Only 39 articles were reviewed, and case series, case report, reviews and reports were excluded. Research reviewed include the epidemiology of substance abuse, genetics, treatment and its relation to health behaviour, and health management. Studies have shown that more males than females use drugs. There was also a high prevalence of blood-bourne virus diseases and sexually transmitted diseases among drug users. Two studies showed some genetic polymorphism (Cyp 3a4 gene and FAAH Pro129Thr) among heroin and amphetamine users respectively that may contribute to drug dependence. Study on pharmacological treatment for substance abuse were limited to methadone and it was shown to improve the quality of life of heroin dependant patients. Alternative treatments such as acupunture and spiritual approach play a role in the management of substance abuse. Data also showed that treatment centres for substance abuse are lacking facilities for screening, assessment and treatment for medical illness related to substance use, e.g. Hepatitis C and tuberculosis. Studies on the effectiveness of current drug rehabilitation centres were inconclusive.
- Critical involvement of 5-HT2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats. [JOURNAL ARTICLE]
- Psychopharmacology (Berl) 2014 Nov 25.
Rats emit various distinct types of ultrasonic vocalizations (USV), with high-frequency 50-kHz USV typically occurring in appetitive situations being elicited by administering drugs of abuse, most notably amphetamine (AMPH), possibly reflecting drug wanting/craving and/or liking.Because 50-kHz USV emission is, at least in part, dopamine (DA) dependent and 5-HT2C agonists inhibit DA neurotransmission, we hypothesized that AMPH-induced 50-kHz USV can be attenuated by pretreatment with a 5-HT2C agonist.In experiments I and II, a dose-response curve for AMPH-induced 50-kHz USV was established, and the partial dependency of AMPH-induced 50-kHz USV on DA neurotransmission was validated by pretreatment with the D2-antagonist eticlopride. In experiment III, rats were pretreated with the 5-HT2C agonist CP 809,101 (0.0, 0.3, 1.0, 3.0, and 10 mg/kg), while in experiment IV, CP 809,101 (3.0 mg/kg), the 5-HT2C antagonist SB 242084 (1.0 mg/kg), or the combination of the two, was applied before AMPH administration (2.0 mg/kg). Finally, in experiment V, rats were treated with SB 242084 (0.0, 0.1, 0.3, and 1.0 mg/kg) only, i.e., in absence of AMPH.The 5-HT2C agonist CP 809,101 dose-dependently blocked AMPH-induced 50-kHz USV, most notably trills, a call subtype that is considered to exclusively reflect a positive affective state, while the 5-HT2C antagonist SB 242084 induced opposite effects. Moreover, SB 242084 induced 50-kHz USV by its own.5-HT2C receptors are critically involved in AMPH-induced 50-kHz USV, with 5-HT2C antagonism resulting in a stimulant-like effect. Attenuation of drug wanting/craving and/or liking by coadministration of a 5-HT2C agonist could be a translational pharmacodynamic biomarker.
- In vitro cytochrome P450 inhibition potential of methylenedioxy-derived designer drugs studied with a two-cocktail approach. [JOURNAL ARTICLE]
- Arch Toxicol 2014 Nov 23.
In vitro cytochrome P450 (CYP) inhibition assays are common approaches for testing the inhibition potential of drugs for predicting potential interactions. In contrast to marketed medicaments, drugs of abuse, particularly the so-called novel psychoactive substances, were not tested before distribution and consumption. Therefore, the inhibition potential of methylenedioxy-derived designer drugs (MDD) of different drug classes such as aminoindanes, amphetamines, benzofurans, cathinones, piperazines, pyrrolidinophenones, and tryptamines should be elucidated. The FDA-preferred test substrates, split in two cocktails, were incubated with pooled human liver microsomes and analysed after protein precipitation using LC-high-resolution-MS/MS. IC50 values were determined of MDD showing more than 50 % inhibition in the prescreening. Values were calculated by plotting the relative metabolite concentration formed over the logarithm of the inhibitor concentration. All MDD showed inhibition against CYP2D6 activity and most of them in the range of the clinically relevant CYP2D6 inhibitors quinidine and fluoxetine. In addition, the beta-keto compounds showed inhibition of the activity of CYP2B6, 5,6-MD-DALT of CYP1A2 and CYP3A, and MDAI of CYP2A6, all in the range of clinically relevant inhibitors. In summary, all MDD showed inhibition of the activity of CYP2D6, six of CYP1A2, three of CYP2A6, 13 of CYP2B6, two of CYP2C9, six of CYP2C19, one of CYP2E1, and six of CYP3A. These results showed that the CYP inhibition by MDD might be clinically relevant, but further studies are needed for final conclusions.
- Khat chewing among Ethiopian University Students- a growing concern. [JOURNAL ARTICLE]
- BMC Public Health 2014 Nov 21; 14(1):1198.
Khat has amphetamine like effect. Students chew khat to stay alert. It has various negative physical, mental, social and cognitive effects. Poor academic performance has been associated with khat. The purpose of this study was to determine the prevalence and identify factors associated with khat chewing among Ethiopian University students.A cross sectional study was conducted on Bahir Dar University Students. A self-administered questionnaire was completed by 3268 students. Proportion was calculated to estimate prevalence of khat chewing. Logistic regression was used to identify factors associated with khat chewing.Lifetime prevalence of khat chewing was 24% (95% Confidence Interval: 22.5%, 26.6%). Half of these are current khat users with a prevalence of 12.7% (95% Confidence Interval: 11.5%, 13.9%). Male students Adjusted Odds Ratio (AOR) = 3.3(95% Confidence Interval: 1.8, 6.0), students living in off campus housing AOR = 3.0(95% Confidence Interval: 1.5, 6.0), students who have khat user friends AOR = 4.2(95% Confidence Interval: 2.6, 6.9), and students who perceive khat use improves academic performance AOR = 6.6 (95% Confidence Interval: 4.6, 9.5) are more likely to use khat.Prevalence of current use of khat reported in this study is higher than recent study done on university students in Ethiopia and heavily influenced with peer practice.
- Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine. [JOURNAL ARTICLE]
- J Addict Res Ther 2014; 5(2):176.
Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS 'elated' scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3-4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous preclinical and human studies, the data suggest that adenosine modulating drugs may have value in the treatment of stimulant use disorders.
- Prescription medication misuse among opioid dependent patients seeking inpatient detoxification. [JOURNAL ARTICLE]
- Am J Addict 2014 Nov 19.
Opioid related morbidity and mortality is heightened in context to the concomitant use of psychotropic medications. The aim of this project was to examine the extent to which opioid dependent patients seeking detoxification are using and misusing specific psychotropic agents.As part of a quality assurance/improvement project, we systematically assessed prospectively consecutive admissions to a public detoxification program using a self-report questionnaire to query for specific psychotropic medication use. Patients were asked about having a current prescription, appropriate use, and/or medical misuse (higher doses, using without prescription) of amphetamine salts, clonazepam, clonidine, gabapentin, and pregabalin.We had data on 196 admissions including 162 patients with opioid dependency. Patients receiving detoxification from opioids compared to alcohol had statistically significant higher rates of medication misuse (30% vs. 0%, respectively; χ(2) = 12.8, p < .0003). Of opioid dependent patients receiving prescription medication, 28% reported using higher amounts of each medication than prescribed. Of opioid patients, 10% self-reported misusing clonidine, 22% gabapentin, 7% pregabalin, 25% clonazepam, 11% amphetamine salts, and 36% any of these medications.Despite the "nonaddictive nature" of some medications (eg, gabapentin, clonidine), high rates of medication misuse in opioid dependent patients admitted for detoxification was found and appeared similar to rates of misuse among controlled substances such as clonazepam and amphetamine salts. These data suggest that opioid dependent patients should be queried for the appropriate use of prescribed medications and that practitioners need to monitor for medication misuse in opioid dependent patients. (Am J Addict 2014;XX:1-5).
- Recreational drugs and HIV in Europe: current use of recreational drugs and principal HIV guidelines related recommendations. [Journal Article]
- J Int AIDS Soc 2014; 17(4 Suppl 3):19831.
Recreational drug consumption has been associated with both higher rates of risk activities related to HIV transmission and also worse adherence and management of HIV patients under HAART treatment. Moreover, relevant interactions may be present in patients under HAART treatment. Our aim is to present the European trends of drug consumption per country and age groups and assess the way drug consumption is addressed in general HIV guidelines.Last 12-month prevalence drug use was obtained from the European Monitoring Centre for Drugs and Drug Addiction for the four most consumed drugs (cannabis, cocaine, amphetamines, ecstasys). Consumption rates were collected and analyzed by country and age. Principal HIV guidelines were assessed to identify the degree of incorporation of drug use issues at three levels: transmission risk, adherence to the HAART and management of interactions.(a) WHO; (b) EACS; (c) BHIVA; (d) US DHHS; (e) IAS-USA; (f) GESIDA; (g) French CPG; (h) Italian CPG.Data on drugs of abuse consumption was obtained from 29 European countries, with results showing relevant drug utilization in Europe. Cannabis was the most frequent drug across all countries, with 10 countries over 5% of prevalence over the last year. Other drugs prevalence accounted for about 0.5-1%, reaching up to: 2.1% for cocaine in Spain, 1.4% for ecstasy in the Netherlands and 1.1% for amphetamines in Estonia. 15-24 and 25-34 years old subgroups had the highest prevalence, although notable use of cannabis and cocaine was also found in the 35-44 and 45-54 subgroups. From the eight guidelines assessed, six considered recreational drugs at any point. Recommendations for specific drugs were given in 50% of the guidelines. From those guidelines addressing drug consumption: three assessed risk habits which related to transmission risk, six appraised issues on adherence to HAART and five comprised data on interactions between recreational drugs and HAART. Additionally, five guidelines mentioned drugs in the context of other issues, such as sexual dysfunction or HIV-associated neurocognitive impairment.Use of recreational drugs is frequent in Europe, not only in the younger population but also in other unexpected older subgroups. The scarce information found in the guidelines has a potential implication for patients and clinicians; therefore, there is a need to include specific recommendations about the clinical management of people living with HIV who use recreational drugs.
- [Amphetamine abuse and drug interactions.] [JOURNAL ARTICLE]
- Ugeskr Laeger 2014 Nov 3; 176(45)
Party drug consumption is a growing problem in Denmark. Often these drugs are taken in combination. In this article we review the pharmacodynamic and pharmacokinetic interactions between amphetamine, other illicit drugs and prescription medicine.
- Cross-generational trans fat intake modifies BDNF mRNA in the hippocampus: Impact on memory loss in a mania animal model. [JOURNAL ARTICLE]
- Hippocampus 2014 Nov 14.
Recently, we have described the influence of dietary fatty acids (FA) on mania-like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)-induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short- (1h) and long- (24h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF- mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA ratio. Interestingly, our data showed a positive correlation between brain-derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2) =0.53; P=0.000/ r(2) =0.32; P=0.011, respectively), as well as a negative correlation between PC and DAT levels (r(2) =0.23; P=0.015). Our findings confirm that provision of n-3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania-like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions. This article is protected by copyright. All rights reserved.