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PubMedDate not supplied

Determination of pyrolysis products of smoked methamphetamine mixed with tobacco by tandem mass spectrometry.

This study examines the pyrolysis products of smoked methamphetamine mixed with tobacco that was trapped with a C8 adsorbent cartridge and then detected by gas chromatography-tandem mass spectrometry. According to the results, the mainstream smoke contains 2-methylpropyl-benzene, 2-chloropropyl-benzene, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 3-ethyl-phenol, methamphetamine, dimethylamphetamine, hydroquinone, 3-methyl-5-(1-methylethyl)-methylcarbamate phenol, N-methyl-N-(2-phenylethyl)-acetamide, 4-(3-hydroxy-1-butenyl)-3,5,5-trimethyl-2-cyclohexene-1-one, propanoic acid, N-acetylmethamphetamine, phenyl ester, and furfurylmethylamphetamine. In addition, the compounds in sidestream smoke are 2-propenyl benzene, phenylacetone, methamphetamine, dimethylamphetamine, benzyl methyl ketoxime, 3,4-dihydro-2-naphthalenone, N-folmyamphetamine, N-acetylamphetamine, bibenzyl, N-folmylmethamphetamine, N-acetylmethamphetamine, N-propionymethamphetamine, and furfurylmethylamphetamine. Moreover, the presence of methamphetamine promotes the oxidation of the tobacco components.

Drug Interactions↗

PubMed2003

Quantitative analysis of desmethylselegiline, methamphetamine, and amphetamine in hair and plasma from Parkinson patients on long-term selegiline medication.

Hair and plasma from patients on long-term selegiline medication were analyzed to evaluate the relationships between plasma and hair melanin concentrations and the incorporation of the selegiline metabolites methamphetamine and amphetamine in hair, and to evaluate hair analyses for determining compliance in medication. Analyses were performed on both the whole hairs, as well as pigmented and non-pigmented hairs from gray-haired patients. Melanin was quantitated by spectrophotometry, and metabolites were quantitated by gas chromatography-mass spectrometry. Concentrations in pigmented and non-pigmented hairs differed significantly for both methamphetamine (p < 0.01) and amphetamine (p < 0.02), with mean concentration ratios being 3.69 +/- 1.88 and 2.95 +/- 1.16 for methamphetamine and amphetamine, respectively. Segmental analysis indicated that some patients had not been compliant with medication. We concluded that the incorporation of methamphetamine and amphetamine into hair of single individuals shows a preference for pigmented hairs over white hairs and that segmental analysis of hair may be useful when measuring compliance with medication.

Aged↗

PubMed2005

Potential marker for smoked methamphetamine hydrochloride based on a gas chromatography-mass spectrometry quantification method for trans-phenylpropene.

Residue from smoked methamphetamine hydrochloride contains pyrolytic products that are detectable by gas chromatography-mass spectrometry (GC-MS). A validated GC-MS method was developed for the determination of trans-phenylpropene, a pyrolytic product of methamphetamine HCl, in residue of smoked drug as well as in human urine. trans-Phenylpropene and an isomeric internal standard, 2-phenylpropene, were extracted from urine using n-hexane. The method was validated for linearity over a range of 0.1-10 microg/mL with a limit of detection of 0.05 microg/mL, limit of quantification of 0.1 microg/mL, interday accuracy within 10.5%, intraday accuracy better than 3.7%, interday precision of 15.4%, intraday precision of 14.4%, and recovery of 89.1%. The method was applied to the detection of trans-phenylpropene found in the residue of methamphetamine HCl heated beyond its melting temperature on aluminum foil under simulated smoking conditions. The method is applicable to the detection of trans-phenylpropene in urine as a potential marker for smoked methamphetamine HCl abuse.

Biomarkers↗

PubMed2006

Validation of a headspace GC method for the analysis of a pyrolytic product of methamphetamine in urine.

A method has been developed and validated using headspace GC-FID for the identification of 1-phenylpropene in urine. This compound is a pyrolytic product of methamphetamine that has been previously proposed as a marker for smoked methamphetamine. The instrumentation used is the same as employed for blood alcohol determination. The extraction-free procedure is rapid, simple, and quantitative using 2-phenylpropene as the internal standard. The method was validated for linearity over a range of 0.1-20 microg/mL with a limit of detection of 0.05 microg/mL, limit of quantification of 0.1 microg/mL, interday accuracy within 3.2 to -5.3%, intraday accuracy better than 7.5%, interday precision of 7.5 to 10.7%, intraday precision of 2 to 8.6%, and recovery above 80%. For the robustness determination in urine, the accuracy of four different sources of urine at the mid control level (1 microg/mL) ranged from 1.6 to 19% error. The % relative standard deviation of the different urine sources ranged from 3.1 to 11%. Urine samples from nine methamphetamine-positive cases investigated by the Office of the Chief Medical Examiner of West Virginia were included in the study. 1-Phenylpropene was found in two methamphetamine-positive cases (0.25 and 0.44 microg/mL).

Adult↗

PubMed2005

Longitudinal patterns of methamphetamine, popper (amyl nitrite), and cocaine use and high-risk sexual behavior among a cohort of san francisco men who have sex with men.

Most prior studies examining drug use among men who have sex with men (MSM) have been cross-sectional or retrospective and have not determined whether periods of increased drug use are associated with high-risk sexual behavior at the individual level. In this article, we describe patterns of use of methamphetamines, poppers, and sniffed cocaine and sexual risk behavior among 736 San Francisco MSM enrolled in the EXPLORE study and followed for up to 48 months. In longitudinal analysis, use of methamphetamines, poppers, and sniffed cocaine declined during follow-up. However, compared with older participants, younger participants were more likely to increase their drug use over time. Results of conditional logistic regression demonstrated that high-risk sexual behavior was more common during reporting periods characterized by increased methamphetamine, poppers, or sniffed cocaine use. This within-person analysis found that compared with periods of no drug use, periods of both light drug use (less than weekly use of drugs) and heavier drug use (at least weekly use of at least one drug) were significantly associated with increased risk of engaging in unprotected anal sex with an HIV-positive or unknown-status partner. These results suggest that even intermittent, recreational use of these drugs may lead to high-risk sexual behavior, and that, to reduce and prevent risks of HIV, no level of use of these drugs should be considered "safe." HIV prevention interventions should target MSM who report either light or heavy use of methamphetamines, poppers, and sniffed cocaine.

Adolescent↗

PubMed1998

Enhanced AP-1 binding in brain induced by D1 and D2 agonists in methamphetamine-sensitized rats.

The activator protein-1 (AP-1) binding activities induced by a separate challenge with SKF38393 and quinpirole after 1 weeks' abstinence from chronic methamphetamine (4 mg/kg/day, 14 days) were increased significantly in the striatum, nucleus accumbens and cingulate cortex compared with the saline-treated controls. Quinpirole-, but not SKF38393-induced AP-1 binding activities were still significantly higher after a 4-week abstinence period in the chronic methamphetamine group than in the chronic saline control group. Downward sniffing, which occurred following a quinpirole-challenge, was significantly intensified after both a 1 and 4 weeks' abstinence from chronic methamphetamine. These results indicate that chronic administration of methamphetamine induces alterations of the interactions of dopamine D1 and D2 receptors which are reflected as enhanced AP-1 binding activities.

Animals↗

PubMed2004

Spontaneous intracerebral hemorrhage related to methamphetamine abuse: autopsy findings and clinical correlation.

A healthy 31-year-old male abstinent from drug abuse during his recent incarceration developed slurred speech, a severe headache, and left-sided hemiparesis prior to his eventual death 9.5 hours after inhalation of methamphetamine. On postmortem examination, inspection of the brain revealed bilateral subarachnoid hemorrhage, with a prominent intralobar hemorrhage centered within the right frontal cerebral hemisphere. No evidence of vasculitis, infarction, intraventricular hemorrhage, or ruptured aneurysm could be observed. While this is not the first report of a methamphetamine-related stroke, this report describes the autopsy findings of an intracerebral hemorrhage secondary to methamphetamine abuse on autopsy and compares the findings and antemortem history to previously reported methamphetamine cerebral vascular deaths.

Adult↗

PubMed2005

The nature, time course and severity of methamphetamine withdrawal.

AIMS: To characterize the natural history of methamphetamine withdrawal during the first 3 weeks of abstinence. DESIGN: Cross-sectional study with comparison group. Setting A substance use treatment facility in Chiang Mai Province, Thailand. PARTICIPANTS: The sample comprised 21 in-patients undergoing treatment for methamphetamine dependence. Nine age- and sex-matched non-dependent individuals provided comparison data. MEASUREMENTS: Instruments including: the Amphetamine Withdrawal Questionnaire, a modified version of the Cocaine Selective Severity Assessment, Clinical Global Impression scale and the St Mary's Hospital Sleep Questionnaire were completed daily for the first 3 weeks of abstinence. FINDINGS: Methamphetamine withdrawal severity declined from a high initial peak within 24 hours of the last use of amphetamines reducing to near control levels by the end of the first week of abstinence (the acute phase). The acute phase of amphetamine withdrawal was characterized by increased sleeping and eating, a cluster of depression-related symptoms and less severely, anxiety and craving-related symptoms. Following the acute withdrawal phase most withdrawal symptoms remained stable and at low levels for the remaining 2 weeks of abstinence. CONCLUSIONS: This study has provided evidence of a methamphetamine withdrawal syndrome that can be categorized into two phases, the acute phase lasting 7-10 days during which overall symptom severity declined in a linear pattern from a high initial peak, and a subacute phase lasting at least a further 2 weeks.

Acute Disease↗

PubMed2006

An outbreak of hepatitis B virus infection among methamphetamine injectors: the role of sharing injection drug equipment.

AIM: To identify risk factors for acute hepatitis B virus (HBV) infection among Wyoming methamphetamine injectors. DESIGN: A case-control study conducted in the setting of an outbreak. SETTING: A county in central Wyoming, United States. PARTICIPANTS: Cases were identified through surveillance and contact tracing and were defined as Natrona County, Wyoming, residents who were either symptomatic or confirmed serologically to be acutely infected with HBV during January-August, 2003. Controls were susceptible to HBV infection. All participants identified themselves as methamphetamine injectors. MEASUREMENTS: Participants were administered a survey that inquired about risk factors for HBV infection, including drug use practices and sexual behaviors. Controls were also tested serologically for acute HBV infection. FINDINGS: Among the 18 case-patients and 49 controls who participated in the study, sharing water used to prepare injections and/or rinse syringes was associated with HBV infection (94% of case-participants versus 44% of controls; OR = 21.9, 95% CI: 2.7, 177.8), as was sharing cotton filters (89% of case-participants versus 52% of controls; OR = 7.4, 95% CI: 1.5, 35.6); sharing syringes was not statistically associated. In logistic regression models adjusted for age, sex, and interview site, sharing rinse water and sharing cotton remained statistically associated. CONCLUSIONS: Methamphetamine use has become increasingly prevalent in the United States. Our findings highlight the need for awareness of risks associated with injection drug use and sharing behaviors. Enhanced hepatitis B vaccination programs and educational campaigns that target methamphetamine injectors specifically, including those living in rural areas, should be developed and implemented.

Adult↗

PubMed1983

Effects of subchronic treatment of methamphetamine haloperidol on the rat brain levels of GABA, glutamate and aspartate.

Centrally active amino acids (GABA, glutamate, aspartate) were assayed enzyme-fluorometrically in five brain regions of the rat after a 16-day administration of methamphetamine (2.5 mg/kg, i.p.) and haloperidol (2.5 mg/kg, i.p.), or both agents together. Methamphetamine caused no statistically-significant changes in the GABA contents in any brain areas, a significant decrease in the glutamate content of the striatum, hippocampus and midbrain and an increase in the aspartate content of the hypothalamus. Haloperidol treatment resulted in no changes in the GABA content, a significant decrease in the glutamate content of the striatum and a significant increase in the aspartate content in the frontal cortex. The treatment with both agents caused a significant decrease in the GABA content of the hypothalamus. The combined administration normalized a lowering of the glutamate levels in the striatum caused by methamphetamine and haloperidol, respectively, and increased the level of aspartate in the hypothalamus caused by methamphetamine and in the frontal cortex caused by haloperidol.

Animals↗

PubMed1992

Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation-increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation-increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime.

Analysis of Variance↗

PubMed2006

Comparison of monoamine and corticosterone levels 24 h following (+)methamphetamine, (+/-)3,4-methylenedioxymethamphetamine, cocaine, (+)fenfluramine or (+/-)methylphenidate administration in the neonatal rat.

We have previously shown that neonatal administration of (+/-)3,4-methylenedioxymethamphetamine and (+)fenfluramine produce deficits in spatial and path integration learning, whereas (+)methamphetamine causes deficits in spatial learning. Conversely, cocaine and (+/-)methylphenidate have no effect on either form of learning following neonatal administration. The purpose of the present study was to determine whether corticosterone and/or monoamine levels were changed following subcutaneous administration of 10 mg/kg (+)methamphetamine, (+/-)3,4-methylenedioxymethamphetamine, (+)fenfluramine, (+/-)methylphenidate or cocaine every 2 h (total of four injections) on postnatal day 11. Twenty-four hours after the first dose, plasma, striatum and hippocampus were collected. Corticosterone levels were increased in methamphetamine-, fenfluramine-, methylenedioxymethamphetamine- and methylphenidate-treated rats relative to levels in saline-treated rats, whereas cocaine-treated rats were unaffected. In the striatum and hippocampus, serotonin and 5-hydroxyindolacetic acid were reduced in animals treated with methylenedioxymethamphetamine or fenfluramine, compared with levels in saline controls. Dopamine levels were not changed by any of the drugs, although 3,4-dihydroxyphenylacetic acid was decreased following methylenedioxymethamphetamine or methamphetamine. Minimal effects were seen in neurotransmitter levels following injection of cocaine or methylphenidate. These data suggest that drugs that affect corticosterone and hippocampal serotonin are associated with both spatial learning and path integration deficits, and those that affect corticosterone and 3,4-dihydroxyphenylacetic acid are associated with spatial learning deficits only.

3,4-Methylenedioxyamphetamine↗

PubMed2002

Morphological and biochemical evidence that apomorphine rescues striatal dopamine terminals and prevents methamphetamine toxicity.

Apomorphine, given by a single injection, repeated injections, or by continuous infusion, was tested for neuroprotective effects in mice administered methamphetamine or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in order to induce striatal dopamine (DA) depletion. In the first part of the study, the DA agonist (R)-apomorphine was administered at various doses (1, 5, and 10 mg/kg), 15 min before methamphetamine (5 mg/kg x 3, 2 h apart). Mice were sacrificed 5 days later. In the second part, apomorphine was administered either continuously by subcutaneous minipump (cumulative daily dose of 0.5, 1, and 3.15 mg/kg), or as single, repeated daily injections (up to 5 mg/kg) starting 40 h after an acute administration of MPTP (30 mg/kg). Mice were sacrificed at different time intervals (up to 1 month) following MPTP injection. In all the animals, the integrity of striatal DA terminals was evaluated by measuring striatal DA levels and TH immunohistochemistry. Apomorphine dose-dependently prevented methamphetamine toxicity. These effects were neither due to a decrease in the amount of striatal methamphetamine nor to the hypothermia, and they were not reversed by the DA antagonist haloperidol. Moreover, chronic, continuous (but not pulsatile) administration of apomorphine rescued damaged striatal dopaminergic terminals. These findings confirm a protective effect of apomorphine that also consists of a neurorescue of damaged striatal DA terminals. This suggests a new hypothesis about the long-term benefits observed during continuous apomorphine administration in Parkinson's disease patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Irreversible inhibition of CYP2D6 by (-)-chloroephedrine, a possible impurity in methamphetamine.

(+)- and (-)-Chloroephedrine, and their respective aziridines, cis- and trans-1,2-dimethyl-3-phenylaziridine, have been reported present in clandestinely synthesized methamphetamine. Since methamphetamine and structurally related compounds are potential substrates for human liver CYP2D6, the possible interaction of the chloroephedrines with human liver CYP2D6 was evaluated. Computational methods (using Flexidock and HINT in SYBYL) were used to determine the feasibility of (+)- or (-)-chloroephedrine and cis- or trans-1,2-dimethyl-3-phenylaziridine binding in the active site of a three dimensional CYP2D6 molecular model. Although modeling indicates both (+)- and (-)-chloroephedrine would bind comparably to methamphetamine, the binding energies of cis- or trans-1,2-dimethyl-3-phenylaziridine products indicate a preference for trans-1,2-dimethyl-3-phenylaziridine, the product formed from (-)-chloroephedrine. The effects of (+)- and (-)-chloroephedrine on the metabolism of dextromethorphan in human liver microsomes were then experimentally evaluated. (+)-Chloroephedrine (50 micro M) had no effect on human CYP2D6. (-)-Chloroephedrine appeared to be selective for human CYP2D6 versus CYP1A2 and CYP3A4/5. The inhibition of CYP2D6 was time-dependent, not dependent on metabolic activation, and irreversible. It appeared to bind at the active site of CYP2D6 with an apparent K(i) of 226 micro M, with a k(int) of 0.039 min(-1), and a t(1/2) of 23 min. Due to the irreversible nature of this inhibition, this impurity in clandestinely synthesized methamphetamine may be important and warrant further study.

Cytochrome P-450 CYP2D6↗

PubMed1989

Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity.

The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2003

Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence.

This study documented the association between neurocognitive impairment and methamphetamine dependence in a sample of 27 methamphetamine-dependent individuals who achieved 5 to 14 days of continuously monitored abstinence and in 18 control subjects. Methamphetamine-dependent individuals performed significantly worse than control subjects on neurocognitive measures sensitive to attention/psychomotor speed, on measures of verbal learning and memory, and on executive systems measures sensitive to fluency. These findings are the first to demonstrate that methamphetamine dependence is associated with impairments across a range of neurocognitive domains in a sample of users whose abstinence was continuously monitored with the use of urine screening.

Adult↗

PubMed2003

Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review.

Methamphetamine use is on the rise, with an imminent upsurge of abuse and dependence reported across the United States. Currently, preliminary evidence suggests that methamphetamine dependence may cause long-term neural damage in humans, with concomitant deleterious effects on cognitive processes such as memory and attention. This selective review provides an outline and synthesis of studies that assess the neurotoxic mechanisms of methamphetamine, as well as those that evaluate the cognitive sequelae of methamphetamine abuse.

Central Nervous System Stimulants↗

PubMed2006

The methamphetamine-sensitive circadian oscillator (MASCO) in mice.

The suprachiasmatic nucleus (SCN) orchestrates synchrony among many peripheral oscillators and is required for circadian rhythms of locomotor activity and many physiological processes. However, the unique effects of methamphetamine (MAP) on circadian behavior suggest the presence of an SCN-independent, methamphetamine-sensitive circadian oscillator (MASCO). Substantial data collected using rat models show that chronic methamphetamine dramatically lengthens circadian period of locomotor activity rhythms and induces rhythms in animals lacking an SCN. However, the anatomical substrate and the molecular components of the MASCO are unknown. The response to MAP is less well studied in mice, a model that would provide the genetic tools to probe the molecular components of this extra-SCN oscillator. The authors tested the effects of chronic MAP on 2 strains of intact and SCN-lesioned mice in constant dark and constant light. Furthermore, they applied various MAP availability schedules to SCN-lesioned mice to confirm the circadian nature of the underlying oscillator. The results indicate that this oscillator has circadian properties. In intact mice, the MASCO interacts with the SCN in a manner that is strain, sex, and dose dependent. In SCN-lesioned mice, it induces robust free-running locomotor rhythmicity, which persists for up to 14 cycles after methamphetamine is withdrawn. In the future, localization of the MASCO and characterization of its underlying molecular mechanism, as well as its interactions with other oscillators in the body, will be essential to a complete understanding of the organization of the mammalian circadian system.

Animals↗