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PubMed2003

Psychiatric and substance dependence comorbidities, sexually transmitted diseases, and risk behaviors among methamphetamine-dependent gay and bisexual men seeking outpatient drug abuse treatment.

This article describes psychiatric and substance dependence comorbidities, lifetime rates of infectious disease, and reported high-risk sexual behaviors for methamphetamine-dependent, gay and bisexual men at entry to outpatient drug abuse treatment in Los Angeles. Participants' self-reports of high-risk sexual and drug use behaviors and of history of infectious disease status were correlated with diagnostic information from 155 Structured Clinical Interviews for the DSM-IV (SCID). A total of 82 participants met criteria for lifetime depressive disorders; 44 participants met criteria for lifetime anxiety disorders. Compared to those without psychiatric diagnoses, significant differences were observed in lifetime prevalence of sexually transmitted infections among those who have generalized anxiety disorder (higher rates of genital gonorrhea), specific phobia and major depressive disorder (higher rates of oral gonorrhea), social phobia (higher rates of syphilis) and bipolar disorder, type I (higher rates of HIV). Differences in infectious disease prevalence did not correspond to significantly different rates of high-risk sexual behaviors. Findings indicate that gay and bisexual men seeking outpatient treatment for methamphetamine dependence are likely to experience psychiatric comorbidity and to have high rates of infectious disease, including HIV, syphilis and gonorrhea.

Amphetamine-Related Disorders↗

PubMed2002

Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes.

Human immunodeficiency virus (HIV) infection among substance abusers is on the rise worldwide. Psychostimulants, and in particular methamphetamine (METH), have detrimental effects on the immune system as well as causing a progressive neurodegeneration, similar to HIV infection. Many Lentivirinae, including feline immunodeficiency virus (FIV), penetrate into the central nervous system early in the course of infection with astrocytes serving as a reservoir of chronic brain infection. We demonstrate that the FIV-Maryland isolate infects feline primary and cell line (G355-5)-cultured astrocytes only under cell-associated conditions. Infected astrocytes yielded a new astrocytotropic isolate, capable of cell-free infection (termed FIV-MD-A). This isolate contained four amino acid substitutions in the envelope polyprotein resulting in a change in net charge as compared to FIV-MD. Infection for both isolates was dependent upon a functional astrocyte CXCR4 receptor. Methamphetamine increased significantly FIV replication in feline astrocytes for cell-associated infection only, with no effect on peripheral blood mononuclear cells or astrocytes infected with FIV-MD-A. This viral replication was related to proviral copy number, suggesting the effect of METH is at the viral entry or integration into host genome levels, but not at the translational level. Thus, lentiviral infection of the brain in the presence of the psychostimulant METH may result in enhanced astrocyte viral replication, producing a more rapid and increased brain viral load.

Animals↗

PubMed2004

Selective changes in the shapes of parasagittal bands of Aldoc (Zebrin) mRNA in the rat vermis of the cerebellum after repeated methamphetamine injections.

In the cerebellum the mossy and climbing projections, which excite Purkinje cells, display a parasagittal and striped organization. These projections also excite Zebrin (aldolase C: Aldoc) parasagittally. To evaluate the possibility that external stimuli can change the organization of the bands of Aldoc mRNA, we compared the effects of repeated methamphetamine administration on the Aldoc mRNA stripes in the four transverse (anterior, central, posterior and nodular) regions of the vermis with the effects on the glutamate transporter EAAT4 (SCL1A 6) mRNA stripes. In the posterior region the injections four times daily increased the fragmentation of the Aldoc mRNA stripes. The presence of a large amount of fragmentation (forty/cerebellum slice), was accompanied with large lateral dislocations of the Aldoc mRNA stripes. In the central and nodular regions, where the size of the stripe areas decreased significantly the stripes were dislocated laterally. The dislocations of the Aldoc mRNA bands did not occur after a single methamphetamine injection and thus repeated injections were necessary to change the distributions of the lateral bands. In contrast, the distributions of the SCL1A 6 mRNA stripes did not change, even though there was mild fragmentation (six/slice) of the SLC1A 6 mRNA stripes in the anterior region and decreases in the numbers (twelve/slice) in the nodular region. We concluded that excess dopamine selectively changes the location of the Aldoc mRNA compartments in the vermis while the SLC1A 6 mRNA stripes could be changed by other inputs and thus the specific transmitter system might change the specific compartment of the cerebellum.

Amino Acid Transport System X-AG↗

PubMedDate not supplied

Mass selective detection of amphetamine, methamphetamine, and related compounds in urine.

A method is presented for the routine analysis of amphetamine, methamphetamine, and related compounds in urine with gas chromatography coupled with mass spectrometry operated in the selective ion monitoring mode. The analytes are isolated by liquid-liquid extraction and are derivatized with trifluoroacetic anhydride. 3,4-Methylenedioxy-methamphetamine-D(5) is employed as the internal standard. Standard solutions are prepared using spiked urine samples, which are subjected to all phases of sample preparation. Disposable deactivated glass containers are employed throughout the process.

Amphetamines↗

PubMedDate not supplied

Comparison of three commercial amphetamine immunoassays for detection of methamphetamine, methylenedioxyamphetamine, methylenedioxymethamphetamine, and methylenedioxyethylamphetamine.

Three commercial immunoassays for detection of amphetamines in urine, Abuscreen radioimmunoassay (RIA), enzyme-multiplied immunoassay technique (EMIT), and the TDx fluorescence polarization immunoassay (FPIA), have been investigated for detection of methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDE). Blank urine was spiked with 0.1 to 3000 micrograms/mL amphetamine analog and used as sample in the assays. With the RIA and FPIA, MDA displayed a higher cross-reactivity to amphetamine than other analogs, but with EMIT, methamphetamine was relatively similar to amphetamine while MDA, MDMA, and MDE were less reactive. The high specificity RIA and the EMIT confirmation reagents for urine amphetamines produced significant, but relatively minor, reduction in the detectability of these analogs. The variation in cross-reactivity seen between the different assays suggests that RIA, EMIT, and FPIA antibodies have different recognition sites; however, all three immunoassays do detect the illicit amphetamine analogs to varying degrees.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Simultaneous determination of methamphetamine and its metabolites in monkey urine by gas chromatography/mass spectrometry with selected ion monitoring.

A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method has been developed for the simultaneous analysis of methampthetamine and its metabolites (amphetamine, p-hydroxymethamphetamine, and p-hydroxyamphetamine) in monkey urine. The method has been applied to the analysis of urine samples from monkeys singly and repeatedly treated with methamphetamine. We have shown that the repeated administration of methamphetamine causes the reduction of urinary excretion of aromatic hydroxylated metabolites. We propose that the method described here can be used for biological monitoring.

Amphetamine↗

PubMedDate not supplied

Postmortem tissue methamphetamine concentrations following selegiline administration.

Selegiline is a relatively new antiparkinson's drug whose metabolites include methamphetamine and amphetamine. A 72-year-old female with apparently suicidal intentions was found dead at her residence. The cause of death was listed as coronary heart disease with a history of polypharmacy. The tissue methamphetamine and amphetamine concentrations resulting from selegiline administration are presented in this report.

Aged↗

PubMed1994

Urinary methamphetamine concentration following famprofazone administration.

A 37-year-old man had a considerable concentration of methamphetamine in his urine, but he denied taking any abused drug. It was found that he took a pain killer that contains famprofazone, a relatively strong analgesic whose metabolites include methamphetamine and amphetamine. The human urinary metabolism of famprofazone was investigated. Immunoassay was used as a preliminary test, and gas chromatography with flame-ionization detection and gas chromatography-mass spectrometry were used for quantitation and confirmation.

Adult↗

PubMedDate not supplied

alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: I. Physical characterization and GC-MS analysis of BNMPA and anticipated metabolites in urine.

alpha-Benzyl-N-methylphenethylamine (BNMPA) is an impurity of illicit methamphetamine synthesis. We synthesized BNMPA and three of its anticipated metabolites: N-demethyl-alpha-benzyl-phenethylamine, 1,3-diphenyl-2-propanone, and 1,3-diphenyl-2-propanol. The purity and structure of these compounds and their heptafluorobutyric anhydride (HFBA) derivatives were confirmed by melting point, gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance. A GC-MS method to detect these compounds in urine, using liquid-liquid extraction and derivatization with HFBA, was developed. Interference studies showed BNMPA and its proposed metabolites to be well-resolved from other common phenethylamine drugs and Health and Human Services-Forensic Urine Drug Testing required analytes. The limit of detection of BNMPA and its metabolites was 2.5 ng/mL; the limit of quantitation (LOQ) of the four compounds was 25 ng/mL. The calibration curves were generally linear from 25 to 500 ng/mL. Typical within-run coefficients of variation (CVs) at the LOQ ranged from 13 to 20% (n = 8). Between-run CVs over 1 month at 25 ng/mL were from 9 to 28%, and at 500 ng/mL, they were from 2.6 to 3.9%. The detection of BNMPA or its metabolites in urine samples may provide a marker of use of illicitly synthesized methamphetamine.

Aluminum↗

PubMedDate not supplied

Enantiomeric determination of amphetamine and methamphetamine in urine by precolumn derivatization with Marfey's reagent and HPLC.

An analytical method was developed for enantiomeric determination of amphetamine and methamphetamine in human urine. The enantiomers were isolated from urine by solid-phase extraction, and diastereomers were formed by derivatization with the chiral Marfey's reagent (1-fluoro-2,4-dinitrophenyl-5-l-aniline amide). The diastereomers were separated by reversed-phase high-performance liquid chromatography in a water/methanol mobile phase and detected by absorbance spectrophotometry at 340 nm. Linear standard curves were obtained for all four enantiomers over a concentration range of 0.16-1.00 mg/L in urine. The detection limit was 0.16 mg/L urine for each enantiomer, and the limit of quantitation was 0.40 mg/L. The urine of 10 decedents was analyzed by this method and by a previously published precolumn derivatization procedure using (-)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as the derivatizing agent and fluorescence detection. Comparison of the results of the two methods by linear regression showed comparable results for both d-amphetamine and d-methamphetamine. Neither method detected the presence of the l-enantiomers in the urine samples.

Alanine↗

PubMedDate not supplied

Toxicological findings in a fatal ingestion of methamphetamine.

This paper presents the case history of a fatality caused by the complications brought about by the presence of methamphetamine and ethanol. Drug concentrations are reported from samples obtained approximately 15 min after the subject was last observed to be chewing what was then believed to be gum, 3 h after the initial toxic symptoms were displayed, 6, 11, and 22 h later. The subjects conditions deteriorated over the course of this time, and he was declared dead 33 h after the initial display of toxic symptoms. The toxicological findings and concentration levels of the reported biological specimens concurred with the expected findings in a case of methamphetamine toxicity.

Adult↗

PubMed1999

Simultaneous determination of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA) enantiomers by GC-MS.

A method is described for the simultaneous determination of the ratio of l- and d-enantiomers of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) in urine. The assay uses liquid-liquid extraction followed by derivatization with trifluoroacetyl-l-prolyl chloride (l-TPC) and analysis by gas chromatography-mass spectrometry. The assay was developed using prepared samples containing varying concentrations of each of the analytes over a range of percentages of each enantiomer. Results showed the method to provide accurate and reliable results in samples containing > or = 10 ng/mL amphetamine and methamphetamine and > or = 25 ng/mL MDA, MDMA, and MDEA. The assay was used to analyze urine samples from subjects of a controlled MDMA study. Results for each of the eight subjects showed a greater percentage of the l-enantiomer of MDMA initially, and the percentage increased with time postdose. Analysis of the metabolite MDA revealed that the proportion of d-enantiomer was initially greater than the l-enantiomer followed by a gradual increase in the proportion of l-enantiomer until it exceeded the amount of the d-enantiomer. In all cases, the l-MDA exceeded the d-MDA within the first 36 h postdose.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Rapid analysis of amphetamine, methamphetamine, MDA, and MDMA in urine using solid-phase microextraction, direct on-fiber derivatization, and analysis by GC-MS.

A rapid, sensitive, and solvent-free procedure for the simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine was developed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode. A headspace vial containing the urine sample, NaOH, NaCl, and amphetamine-d3 as the internal standard was heated at 100 degrees C for 20 min. A polydimethylsiloxane fiber was maintained in the vial headspace for 10 min in order to adsorb the amphetaminic compounds, which were subsequently derivatized by exposing the fiber to trifluoroacetic anhydride for 20 min in the headspace of another vial maintained at 60 degrees C for 20 min. The trifluoroacetyl derivatives were desorbed in the GC injection port for 5 min. Several parameters were considered during the method optimization process. These included a comparison of SPME with or without headspace, the required derivatization procedure, and the influence of temperature on the headspace extraction and derivatization methods. The optimized method was validated for the four compounds tested. Calibration curves showed linearity in the range 50-1000 ng/mL (r = 0.9946-0.9999). Recovery data were 71.89-103.24%. The quantitation limits were 10 ng/mL for amphetamine and methamphetamine and 20 ng/mL for MDA and MDMA. All of these data recommend the applicability of the method for use in the analytical routine of a forensic laboratory.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Rapid and simple quantitation of methamphetamine by using a homogeneous time-resolved fluoroimmunoassay based on fluorescence resonance energy transfer from europium to Cy5.

A rapid and simple homogeneous time-resolved fluoroimmunoassay based on fluorescence resonance energy transfer from europium (Eu) to cyanine dye (Cy5) has been developed for the quantitation of methamphetamine. In this assay, Eu chelate was labeled to a conjugate of methamphetamine and bovine serum albumin (MA-BSA), as an energy donor, and Cy5 was labeled to anti-MA as an energy acceptor. The close proximity between the two labels in the immunocomplex permits energy transfer from the excited Eu(3+) donor. Therefore, by measuring the sensitized emission of Cy5 with the time-resolved assay, immunocomplex of MA-BSA and anti-MA can be measured in the homogeneous solution without separation steps within 30 min. By a competitive immunoassay, MA could be assayed in the range 0.1-1,000 ng/mL. The intra-assay variations were 5.4-14.8% at 5 different concentrations. When urine or serum samples were examined, the quenching of Eu fluorescence was observed, but the acceptor-to-donor ratio constantly depended upon the dilution of samples. Twenty urine samples were assayed, and the data showed a good correlation to those obtained by gas chromatography (r = 0.94). The homogeneous assay using Eu-Cy5 energy transfer is time-saving without any washing procedures and is suitable for screening drugs that are commonly abused.

Calibration↗

PubMed1999

The effect of lithium on methamphetamine-induced regional Fos protein expression in the rat brain.

Lithium has been used widely for the treatment of manic states. Since amphetamines produce effects in humans similar to the symptoms of idiopathic mania, amphetamine administration to animals has been proposed as a model of this condition. To investigate the neurobiologic substrates of the antimanic effects of chronic lithium administration, we investigated its effects on methamphetamine-induced regional Fos protein expression in the rat brain. Chronic lithium administration (14 days; serum lithium concentration, 0.41+/-0.02 mEq/l) significantly reduced the number of neuronal nuclei showing immunoreactivity induced by methamphetamine (2mg/kg) in the prefrontal cortex, caudate/putamen, nucleus accumbens, and central nucleus of the amygdala. These results indicate the structural basis in CNS which is responsible for the antimanic effect of lithium.

Animals↗

PubMed2000

18-MC reduces methamphetamine and nicotine self-administration in rats.

In previous studies, 18-methoxycoronaridine (18-MC), a novel iboga alkaloid congener, has been found to decrease the intravenous self-administration of morphine and cocaine in rats. In the present study, 18-MC (1-40 mg/kg, i.p.) dose-dependently decreased the i.v. self-administration of methamphetamine and nicotine. As in the previous studies, drug self-administration was reduced for > or = 24 h after the highest dose of 18-MC. A comparison of 18-MC's interactions with all four drugs of abuse studied so far indicated that 18-MC is least effective in decreasing methamphetamine self-administration and most potent in decreasing nicotine self-administration. The results suggest that a nicotinic antagonist action of 18-MC contributes to its putative anti-addictive efficacy.

Animals↗

PubMed2002

The orbitofrontal cortex in methamphetamine addiction: involvement in fear.

We used Tellegen's Multidimensional Personality Questionnaire (MPQ) harm avoidance (fear) scale and the constraint superfactor as personality measures of inhibitory control and examined their association with glucose metabolism in the orbitofrontal gyrus at rest in 14 recently abstinent methamphetamine-dependent subjects and 22 comparison subjects. Higher MPQ scores were associated with higher relative orbitofrontal gyrus metabolism in the methamphetamine-dependent subjects. There was a tendency towards a negative association for the comparison subjects (test of coincidence of regression lines for the two subject groups: F = 3.3, df = 2,32; = 0.051). These results suggest that the role of the orbitofrontal cortex in inhibitory control can be manifested in stable personality predispositions and further implicate this region in the core characteristics of drug addiction.

Adult↗

PubMed1991

Methamphetamine-induced ischemic colitis.

A 50-year-old woman with acute onset of right lower quadrant pain and hematochezia proved to have segmental ischemic colitis associated with methamphetamine abuse. The diagnosis was established by colonoscopy with biopsy, and abdominal angiography revealed no thrombosis, vasculitis, or vasospasm. The condition resolved within 10 days. Since methamphetamine abuse is increasing, physicians should be aware of its potential to produce intestinal ischemia.

Colitis↗