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PubMed2003

Impacts of federal ephedrine and pseudoephedrine regulations on methamphetamine-related hospital admissions.

AIMS: To determine whether the federal regulation of ephedrine and pseudoephedrine, precursors used in illicit methamphetamine production, reduced methamphetamine-related acute care hospital admissions. DESIGN: ARIMA-intervention time-series analysis. SETTING: California (1983-2000), Arizona and Nevada (1991-2000), USA. MEASUREMENTS: Monthly counts of methamphetamine-related acute care hospital admissions. INTERVENTIONS: Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Products containing pseudoephedrine: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines), used mainly by small-scale producers: regulated October 1996. FINDINGS: In California, the bulk powder regulation stopped a 7-year rise in admissions (1983-89) and reduced them by 35% (P < 0.01). The single ingredient ephedrine regulation stopped a 4-year rise (1992-95) in California, Arizona and Nevada, with 48% (P < 0.01), 71% (P < 0.01) and 52% (P < 0.01) reductions, respectively. The pseudoephedrine products regulation stopped a 2-year rise (1996-97) in California, Arizona and Nevada, with 38% (P < 0.01), 41% (P < 0.05) and 61% (P < 0.01) reductions, respectively. Admissions rose at the end of the study period but were still well below peak 1990s levels. The regulation of ephedrine combined with other active medicinal ingredients had no significant impact in any of the three states. CONCLUSIONS: Regulations targeting precursors used by large-scale producers reduced admissions substantially during the study period. However, the regulation of precursors used primarily by small-scale producers had little, if any, effect.

Drug and Narcotic Control↗

PubMed1995

Estimating hydroxyl radical content in rat brain using systemic and intraventricular salicylate: impact of methamphetamine.

Free radicals have been implicated in the etiology of many neurodegenerative conditions. Yet, because these species are highly reactive and thus short-lived it has been difficult to test these hypotheses. We adapted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quantifiable products, 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. After systemic (100 mg/kg i.p.) or intraventricular (4 mumol) administration of salicylate, the amount of DHBA in striatal tissue correlated with tissue levels of salicylate. After systemic salicylate, the ratio of total DHBA to salicylate in neostriatum was at least 10-fold higher than that observed after central salicylate. In addition, systemic salicylate resulted in considerably higher concentrations of 2,3- and 2,5-DHBA in plasma than in brain. Therefore, a large portion of the DHBA present in brain after systemic salicylate may have been formed in the periphery. A neurotoxic regimen of methamphetamine increased the concentration of DHBA in neostriatum after either central or systemic administration of salicylate. The increase in 2,3-DHBA after the central administration of salicylate was significant at 2 h, but not at 4 h, after the last dose of methamphetamine. These results suggest that (1) when assessing specific events in brain, it is preferable to administer salicylate centrally, and (2) neurotoxic doses of methamphetamine increase the hydroxyl radical content in brain in a time-dependent manner.

Animals↗

PubMed2002

Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain.

Methamphetamine (METH) is an addictive substance that also causes extensive neural degeneration in the central nervous system. Because METH augments striatal substance P (SP) levels, we hypothesized that this neuropeptide plays a role in methamphetamine-induced toxicity and neural damage in the striatum. In this study we present evidence demonstrating that signaling through the neurokinin-1 (NK-1) receptor by SP plays an important role in methamphetamine-induced toxicity in the striatum. We tested the effects of the selective NK-1 receptor antagonists WIN-51,708 and L-733,060 on several markers of dopaminergic terminal toxicity in the mouse striatum. Administration of NK-1 receptor antagonist prevented the loss of dopamine transporters assessed by autoradiography and western blotting, the loss of tissue dopamine assessed by high-pressure liquid chromatography, and the loss of tyrosine hydroxylase, as well as the induction of glial fibrillary acidic protein determined by western blotting. Pre-treatment with NK-1 receptor antagonist had no effect on METH-induced hyperthermia. Pre-exposure of mice to either of the NK-1 receptor antagonists alone was without effect on all of these neurochemical markers. These results provide the first evidence that tachykinins, particularly SP, acting through NK-1 receptors, play a crucial role in the pathogenesis of nigrostriatal dopaminergic terminal degeneration induced by METH. This finding could lead to novel therapeutic strategies to offset drug addictions as well as in the treatment of a number of disorders including Parkinson's and Huntington's diseases.

Androstanes↗

PubMed2005

[Increasing prevalence of amphetamine--and methamphetamine-induced psychosis].

OBJECTIVE: With changed consumer behaviour in the drug scene the psychiatric complications with the derivates of amphetamine increase. In some regions methamphetamin is particularly common. Flashbacks, which can be triggered by psychosocial stress, as well as the age of the usually young patients lead to the differential diagnosis of schizophrenia. METHODS: During the observation period 1998 - 2000 the diagnostic distributions and the psychosocial base data of all patients admitted to the BKH Bayreuth with the clinical picture of a paranoid psychosis, were examined regarding an increase of drug-induced psychosis. RESULTS: Both the number of the treated patients with chronic dependence on methamphetamine as well as acute admissions of patients with drug-induced psychosis increased. Differences to patients diagnosed a schizophrenia could be shown. CONCLUSION: With the further increasing abuse of stimulants like methamphetamine the number of patients with induced psychosis will escalate. Specific settings for treatment will be required to address the addiction as well as the psychosis.

Amphetamine↗

PubMedDate not supplied

Treatment-as-usual in the methamphetamine treatment project.

The Methamphetamine Treatment Project is a multisite trial that compares the effectiveness of eight models of outpatient treatment for methamphetamine dependence to that of the Matrix model. These eight "treatment-as-usual" models represent diverse approaches developed in a variety of settings to serve markedly different populations. The theoretical foundations of these treatments are described as well as the settings in which they are delivered. To facilitate comparisons, details are presented with respect to frequency of group and individual sessions, duration of treatment, therapist qualifications, and access to ancillary services. The populations served by these programs vary with respect to race and ethnicity. Most programs serve primarily non-Hispanic Caucasians, but some programs serve significant proportions of Hispanics, Asians, Pacific Islanders, and Native Americans. Usual route of administration of methamphetamine also varies by site, with snorting, smoking, and injecting each reported as the most common route of administration at one or more sites. The Minnesota model and cognitive-behavioral approaches are most commonly used in these programs, although contingency management and psychodynamic approaches are also represented. The intensive phase of treatment ranges between four and 24 weeks; the number of hours per week of client contact varies between one and 13. This trial will provide the opportunity to test the effectiveness of a wide range of treatments currently in use in community settings.

Central Nervous System Stimulants↗

PubMedDate not supplied

A descriptive analysis of participant characteristics and patterns of substance use in the CSAT methamphetamine treatment project: the first six months.

The CSAT Methamphetamine Treatment Project (MTP) is a multisite study with a two-fold purpose: to assess the feasibility and outcomes generated by a technology transfer of the Matrix treatment model for methamphetamine (MA) abuse into several community-based treatment programs, and specifically to compare outcomes of treatment as usual at each site with outcomes of the Matrix model, as implemented in each site. The study comprises seven sites, geographically situated in Hawaii, Northern and Southern California, and Montana. This article presents a demographic description of the cohort, and describes patterns of drug use, abuse, and related problems among the 169 participants recruited in the first six months of the study, from April through September 1999. Specific analyses presented include: demographic composition of the sample with respect to gender, age, ethnicity, education completed, employment status, and income; primary drug used, and mean percent of days using various drugs including MA, alcohol, and marijuana; and percent of sample reporting various routes of drug administration. Mean baseline Addiction Severity Index composite scores are presented that describe medical, employment, alcohol, drug, legal, family/social, and psychiatric status for the sample. Also presented here are comparisons of this preliminary population to other populations reported in the literature. This early subset of MTP participants is similar to other methamphetamine-abusing populations described in the literature in age, years of education, income, and mean years of use. However, because of its multisite structure and the locations of its constituent sites, the MTP population has greater variation in ethnic makeup than do populations from other studies, offering an opportunity to provide useful new information about drug use patterns and treatment responses in populations not previously studied.

Adult↗

PubMedDate not supplied

Methamphetamine and cocaine users: differences in characteristics and treatment retention.

The use of methamphetamine and cocaine have both produced significant public health problems during the past two decades. Although these powerful psychostimulants have many common acute and chronic effects, there are some important differences in who uses these drugs and the consequences of their use. This article reports on two large cohorts of treatment-seeking cocaine and methamphetamine users who entered treatment at the same facility over the same four-year period of time. Patterns of use differed significantly. Cocaine users have more episodic use patterns, spend more money on purchasing their drugs, and use alcohol more heavily. Methamphetamine users include a higher proportion of women, more frequently use on a daily basis, use marijuana more often, and experience more severe medical and psychiatric consequences. Despite the differences in the stimulant drug effects and consequences, the treatment response to a multicomponent, outpatient program is very similar.

Adolescent↗

PubMedDate not supplied

Overdose of 2.3 grams of intravenous methamphetamine: case, analysis and patient perspective.

The patient-reported toxicity of an overdose of intravenous methamphetamine is described. The authors report the case of a 34-year old man who inadvertently injected himself with approximately 2.3 grams of methamphetamine. The patient reported disorientation, hallucinations, hyperthermia, photophobia, orthostasis and extreme ataxia. He recovered in seven days without apparent sequelae. The case demonstrates the unusual, temporary neurophysiologic consequences of high-dose intravenous methamphetamine.

3,4-Methylenedioxyamphetamine↗

PubMed2000

Cognitive impairment in individuals currently using methamphetamine.

Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non-users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.

Adult↗

PubMedDate not supplied

Methamphetamine abstinence syndrome: preliminary findings.

Retrospective reports suggest that chronic use of methamphetamine is associated with a prolonged abstinence syndrome; however, there are no prospective studies confirming this. Nineteen non-treatment-seeking methamphetamine-dependent volunteers participated in a study of mood during initial abstinence. Moderate levels of depression were reported during the first several days of abstinence, with minimal levels reported thereafter. The most prominent symptoms were anhedonia, irritability, and poor concentration. The abstinence syndrome associated with methamphetamine dependence varied considerably in intensity and duration but generally was mild and resolved quickly for most individuals.

Adult↗

PubMed2001

Phosphine exposure from a methamphetamine laboratory investigation.

BACKGROUND: Law enforcement personnel may be exposed to a variety of hazardous materials during investigation of clandestine methamphetamine laboratories. CASE REPORT: A 28-year-old forensic specialist investigating a methamphetamine lab was exposed to phosphine without respiratory protection at approximately 2.7 ppm for 20-30 minutes. Shortly following exposure she developed dizziness, cough, headache, and diarrhea, although initial medical evaluation within 1-2 hours was unremarkable. Pulmonary examination at 4 and 7 days postexposure revealed bilateral rhonchi. The cough was worse with exertion, and persisted despite beta-agonist and steroid inhaler treatment. CONCLUSIONS: This is apparently the first published case of symptomatic occupational phosphine exposure in a law enforcement officer during investigation of a methamphetamine laboratory. If phosphine exposure is suspected, the possibility of delayed pulmonary toxicity should be recognized.

Adult↗

PubMed2000

Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

Amphetamines↗

PubMedDate not supplied

Simultaneous identification of amphetamine and methamphetamine using solid-phase extraction and gas chromatography/nitrogen phosphorous detection or gas chromatography/mass spectrometry.

A method for the simultaneous detection and quantitation of amphetamine and methamphetamine in urine is described. Using solid-phase extraction, amphetamine, methamphetamine, and n-propylamphetamine (internal standard) are extracted from urine samples. Drugs in their free form are identified using gas chromatography/nitrogen-phosphorous detection (GC/NPD), whereas their heptafluorobutyric anhydride derivatives are detected by gas chromatography/mass spectrometry (GC/MS) in the selected ion monitoring (SIM) mode. Limits of detection for both amphetamine and methamphetamine are approximately 35 ng/mL. The procedure is simple, rapid, and suitable for a large number of specimens (25 or more).

Amphetamine↗

PubMedDate not supplied

Serial capillary gas chromatography/Fourier transform infrared spectrometry/mass spectrometry (GC/IR/MS): qualitative and quantitative analysis of amphetamine, methamphetamine, and related analogues in human urine.

A method using serial capillary gas chromatography/Fourier transform infrared spectroscopy/mass spectrometry (GC/IR/MS) for the analysis of derivatized amphetamine, methamphetamine, and related analogues was developed. The GC/IR/MS was configured and optimized with a Hewlett-Packard (HP) 5890A gas chromatograph with a 12-m x 0.32-mm i.d. HP-5 capillary column serially interfaced through an HP 5965A infrared detector to an HP 5970 mass selective detector with a fused-silica 1.2-m x 0.10-mm i.d. column. Urine samples are extracted and derivatized as heptafluorobutyryl (HFBA) derivatives. For quantitation GC/MS in the selected ion monitoring (SIM) mode was used, with D,L-amphetamine-D5 as the internal standard. Gas chromatography/Fourier transform infrared spectrometry (GC/FT-IR) quantitation uses a selected wavelength chromatogram, spectral subtraction, double internal standard method using both D,L-amphetamine-D5 and 4-phenyl butylamine. Sensitivity for the combined GC/MS and GC/FT-IR system for amphetamine and methamphetamine shows limits of linearity of 100 to 5000 ng/mL, a limit of detection of 25 ng/mL, and a limit of quantitation of 98 ng/mL. The overall recovery for amphetamine and related analogues was greater than 85%. Precision studies for concentrations over the range of 200 to 1500 ng/mL showed coefficients of variations ranging from 2.8 to 13.0%. Correlation studies for quantitative GC/MS SIM and GC/FT-IR are greater than 0.98 for amphetamine, methamphetamine, and related analogues. Each analysis includes GC/MS SIM and GC/FT-IR quantitation, qualitative nonselective full spectra GC/FT-IR, and GC/MS scans of HFBA derivatives cross-referenced with an internal drug library, which provides high confidence and a means for the surveillance of amphetamine-like chemical analogues.

Amphetamine↗

PubMedDate not supplied

The determination of amphetamine and methamphetamine in a lyophilized human urine reference material.

The concentrations of amphetamine and methamphetamine in a new lyophilized human urine reference material (RM) were determined at the National Institute of Standards and Technology, in cooperation with the College of American Pathologists. In order to minimize the possibility of undetected bias, two different methods were developed. Both methods were based on isotope-dilution gas chromatography/mass spectrometry (GC/MS) with a deuterium-labeled standard. The first method used a solid phase extractor (SPE) to isolate the analytes, followed by forming the heptafluorobutyryl (HFB) derivatives for measurement by GC/MS. The second method used another kind of SPE to isolate the analytes, followed by forming the N-trifluoroacetyl-1-prolyl chloride (TPC) derivatives for measurement by GC/MS. The RM consists of three levels of amphetamine, three levels of methamphetamine, and a blank. For amphetamine, the concentrations are 291, 558, and 1081 ng/mL of human urine. For methamphetamine, the concentrations are 311, 573, and 1137 ng/mL of human urine.

Amphetamine↗

PubMedDate not supplied

Chirality of methamphetamine and amphetamine from workplace urine samples.

Several positive methamphetamine/amphetamine urine samples were reexamined to determine the chirality of the detected drug or drugs. (S)-N-(Trifluoroacetyl)prolyl derivatives were prepared and analyzed using GC/MS. In one case, pure d-isomers of methamphetamine and amphetamine were detected. In the remainder of the samples involving both drugs, skewed racemates were detected, with the l-isomer of methamphetamine and the d-isomer of amphetamine predominating slightly over their enantiomers. In samples involving amphetamine only, 50:50 mixtures of d- and l-isomers were detected. In no instance was pure i-methamphetamine (from a Vicks inhaler) detected.

Amphetamine↗

PubMedDate not supplied

alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: II. Metabolism and urinary excretion (human).

Methamphetamine is a popular drug of abuse, which is readily synthesized in clandestine laboratories. Illicit synthesis results in the formation of various contaminants. Few impurities have been studied in vivo, and their metabolic fate is unknown. One such impurity is alpha-benzyl-N-methylphenethylamine (BNMPA). The detection of BNMPA or its metabolites in urine samples may provide a marker of use of illicitly synthesized methamphetamine. Benzphetamine is structurally similar to BNMPA. Based on metabolic studies of benzphetamine, we predicted the four major metabolites of BNMPA to be the N-demethyl compound, diphenyl-2-propanone (DP2P), p-hydroxy-N-demethyl BNMPA, and p-hydroxy-BNMPA. One male volunteer ingested 5 mg BNMPA. Seventeen urine specimens were collected over 50 h post ingestion. These specimens were analyzed for BNMPA and its four predicted major metabolites by gas chromatography-mass spectrometry following beta-glucuronidase hydrolysis or acid hydrolysis, liquid-liquid extraction, and derivatization with heptafluorobutyric anhydride. Specimens were also analyzed without hydrolysis to determine the abundance of nonconjugated ("free") metabolites. Only trace amounts of BNMPA and its N-demethyl metabolites were detected, and maximum excretion was from 2 to 4 h post ingestion. In the nonhydrolyzed samples, the phenyl-OH metabolites were also present in only trace amounts. Maximum excretion of DP2P was at 2 h. Following either hydrolysis procedure, phenyl-OH-BNMPA and phenyl-OH-N-demethyl BNMPA were the major metabolites detected. Maximum excretion of these two metabolites occurred at 4 h. With the exception of the parent compound and the N-demethyl metabolite, excretion of metabolites was greater than the limit of detection of this procedure (2.5 ng/mL) up to 21 h post ingestion. Metabolites were detectable in sufficient quantities to serve as an adequate marker of illicit methamphetamine consumption within the preceding 24 h.

Benzphetamine↗

PubMedDate not supplied

Solid-phase extraction in amphetamine and methamphetamine analysis of urine.

A systematic evaluation that compares the recoveries of methamphetamine and amphetamine from spiked urine using C8, C18, strong cation exchanger (SCX), and C8-SCX mixed procedures (solid-phase extraction) is reported. Optimized experimental conditions including pH of the sample, solvent composition, and urine concentration for different solid-phase extraction sorbents were studied. The largest recoveries--greater than 86% for methamphetamine and greater than 88% for amphetamine--were achieved with a mixed adsorbent (C8-SCX) and mixed elution solvent CH2Cl2-i-propanol-NH4OH (78:20:2) at pH 6. The concentration of the urine matrix did not affect the extraction efficiency. The detection limits of methamphetamine and amphetamine in urine were obtained at 0.03 and 0.07 micrograms/mL, respectively, using gas chromatographic-mass spectrometric analysis operated in the electron impact mode.

Adsorption↗