63 research outputs found

    Medical cannabis : an update

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    Acetylcodeine as a Urinary Marker to Differentiate the Use of Street Heroin and Pharmaceutical Heroin

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    Acelylcodeine (ACOD) is a synthesis by product present in street heroin but not in pharmaceutical diacetylmorphine (DAM) as used in the Swiss program Heroin-Assisted Treatment for Opiate Dependent Drug Users (HAT). ACOD was evaluated and validated as an urine marker to detect the consumption of street heroin by HAT participants. A gas chromatography-mass spectrometry method allowing the quantitation of ACOD concentrations as low as 0.2 ng/mL urine has been developed. In opiate-naïve subjects, intravenous (i.v.) ACOD showed a plasma elimination half-life of 237 ± 18 min, urine peak concentrations 2 h after administration, and a detection window of 8 h. Only 0.4 ± 0.1% was excreted unchanged, with codeine (COD) as the main metabolite. ACOD may be formed by transacetylation when i.v. DAM and oral codeine are co-administered. To avoid false-positive results, the calculation of COD/ACOD ratios is recommended. In a study with 105 HAT participants, 14% of the tested urines were ACOD positive. Only a low correlation was found between the anonymously self-declared consumption of street heroin and the ACOD positive rat

    Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes

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    Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the cutoff being 15ng/mL. However, the wide urinary detection window of the long-term metabolite of Δ9-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70mg THC per cigarette. Plasma and urine were collected up to 8h and 11days, respectively. Total THC, 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0ng/mL. Eight puffs delivered a mean THC dose of 45mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2ng/mL, peaking at 2, 2, and 6-24h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120h. Besides high to very high THC-COOH levels (245 ± 1,111ng/mL), THC (3 ± 8ng/mL) and THC-OH (51 ± 246ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes. Figure Urine concentration ranges of delta-9-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in athletes tested cannabispositive (15ng/mL THC-COOH or more; N=81

    Effect of Naloxone-3-Glucuronide and N -Methylnaloxone on the Motility of the Isolated Rat Colon After Morphine

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    The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone on rat colon motility after morphine stimulation was measured. The rat model consisted of the isolated, vascularly perfused colon. The antagonists (10−4 M, intraluminally) and morphine (10−4 M, intra-arterially) were administered from 20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by the luminal outflow. The antagonist concentrations in the luminal and venous outflow were measured by high-performance liquid chromatography. Naloxone-3-glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the luminal outflow to baseline within 10 and 20 min, respectively. These antagonists were then excreted in the luminal outflow and could not be found in the venous samples. Naloxone, produced by hydrolysis or demethylation, was not detectable. In conclusion, highly polar naloxone derivatives peripherally antagonize the motility-lowering effect of morphine in the perfused isolated rat colon, are stable, and are not able to cross the colon-mucosal blood barrie

    Analysis of 3,4-Methylenedioxymethamphetamine (MDMA) and its Metabolites in Plasma and Urine by HPLC-DAD and GC-MS

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    In Europe, the compound 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy, Adam), in addition to cannabis, is the most abused illicit drug at all-night "techno” parties. Methods for the determination of MDMA and its metabolites, 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-dihydroxymethamphetamine (HHMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 3,4-dihydroxyamphetamine (HHA), in biological fluids were established. Plasma and urine samples were collected from two patients in a controlled clinical study over periods of 9 and 22 h, respectively. MDMA and MDA were determined in plasma and urine by reversed-phase high-performance liquid chromatography with diode array detection (HPLC-DAD) after solid-phase extraction on cation-exchange columns. Acidic or enzymatic hydrolysis was necessary to detect HMMA, HMA, HHMA, and HHA, which are mainly excreted as glucuronides. Gas chromatography-mass spectrometry (GC-MS) was used for confirmation. Sample extraction and on-disc derivatization with heptafluorobutyric anhydride (HFBA) were performed on Toxi-Lab SPEC solid-phase extraction concentrators. After administration of a single oral dose of 1.5 mg/kg body weight MDMA, peak plasma levels of 331 ng/mL MDMA and 15 ng/mL MDA were measured after 2 h and 6.3 h, respectively. Peak concentrations of 28.1 µg/mL MDMA in urine appeared after 21.5 h. Up to 2.3 µg/mL MDA, 35.1 µg/mL HMMA, and 2.1 µg/mL HMA were measured within 16-21.5 h. Conjugated HMMA and HHMA are the main urinary metabolites of MDM

    Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

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    Abstract A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted

    Profiles of Urine Samples Taken from Ecstasy Users at Rave Parties: Analysis by Immunoassays, HPLC, and GC-MS

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    The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is increasing throughout the world. They have become popular drugs, especially at all-night techno dance parties (Raves), and their detection is becoming an important issue. Presently, there are no MDMA- or MDA-specific immunoassays on the market, and detection of the designer amphetamines is dependent upon the use of commercially available amphetamine assays. The success of this approach has been difficult to assess because of the general unavailability of significant numbers of samples from known drug users. The objectives of the present study are to characterize the drug content of urine samples from admitted Ecstasy users by chromatographic methods and to assess the ability of the available amphetamine/methamphetamine immunoassays to detect methylenedioxyamphetamines. We found that, when analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD), 64% of 70 urine samples (by gas chromatography-mass spectrometry [GC-MS]: 88% of 64 urine samples) obtained from Rave attendees contained MDMA and/or 3,4-methylenedioxyamphetamine (MDA) alone or in combination with amphetamine, methamphetamine, or other designer amphetamines such as 3,4-methylenedioxyethylamphetamine (MDEA). This suggests that the majority of the Ravers are multi-drug users. At the manufacturer's suggested cutoffs, the Abbott TDx Amphetamine/Methamphetamine II and the new Roche HS Amphetamine/MDMA assays demonstrated greater detection sensitivity for MDMA than the other amphetamine immunoassays tested (Abuscreen OnLine Hitachi AMPS, Abuscreen OnLine Integra AMPS, Abuscreen OnLine Integra AMPSX, CEDIA AMPS, and EMIT II AMPS). There is 100% agreement between each of the two immunoassays with the reference chromatographic methods, HPLC-DAD and GC-MS, for the detection of methylenedioxyamphetamine

    Pharmacokinetics and Excretion of Gamma-Hydroxybutyrate (GHB) in Healthy Subjects

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    In Europe and the United States, the recreational use of gammahydroxy butyric acid (GHB) at dance clubs and "rave” parties has increased substantially. In addition, GHB is used to assist in the commission of sexual assaults. The aim of this controlled clinical study was to acquire pharmacokinetic profiles, detection times, and excretion rates in human subjects. Eight GHB-naïve volunteers were administered a single 25-mg/kg body weight oral dose of GHB, and plasma, urine, and oral fluid specimens were analyzed by using gas chromatography-mass spectrometry (GC-MS). Liquid-liquid extraction was performed after acid conversion of GHB to gamma-butyrolactone. Limits of quantitation of 0.1 (oral fluid), 0.2 (urine), and 0.5 µg/mL (plasma) could be achieved in the selected ion monitoring mode. GHB plasma peaks of 39.4 ± 25.2 µg/mL (mean ± SEM) occurred 20-45 min after administration. The terminal plasma elimination half-life was 30.4 ± 2.45 min, the distribution volume 52.7 ± 15.0 L, and the total clearance 1228 ± 233 µL/min. In oral fluid, GHB could be detected up to 360 min, with peak concentrations of 203 ± 92.4 µg/mL in the 10-min samples. In urine, 200 ± 71.8 and 230 ± 86.3 µg/mL, were the highest GHB levels measured at 30 and 60 min, respectively. Only 1.2 ± 0.2% of the dose was excreted, resulting in a detection window of 720 min. Common side-effects were confusion, sleepiness, and dizziness; euphoria and change of vital functions were not observed. GHB is extensively metabolized and rapidly eliminated in urine and oral fluid. Consequently, samples should be collected as soon as possible after ingestio

    Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

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    A single dose of heroin can reduce stress responses in heroin-dependent patients. Schmidt et al. report that increased amygdala-related functional connectivity during fearful face processing in heroin-dependent patients transiently normalises after a single dose of heroin. This measure may help to assess the efficacy of maintenance treatments in drug addictio

    Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

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    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction
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