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PubMed1993

Treatment of narcolepsy with methamphetamine.

Eight pairs of subjects (each consisting of a narcoleptic and a control matched on the basis of age, sex, educational background and job) were evaluated under the following double-blind, randomized treatment conditions: baseline, placebo, low dose and high dose methamphetamine. Subjects were drug-free for 2 weeks prior to beginning the protocol. Methamphetamine was the only drug taken during the protocol and was given in a single morning dose of 0, 20 or 40-60 mg to narcoleptics and 0, 5 or 10 mg to controls. The protocol was 28 days long, with each of the four treatment conditions lasting 4 days followed by 3 days of washout. Nighttime polysomnography and daytime testing were done during the last 24 hours of each treatment condition. Daytime sleep tendency was assessed with the multiple sleep latency test (MSLT). Daytime performance was assessed with performance tests including a simple, computer-based driving task. Narcoleptics' mean MSLT sleep latency increased from 4.3 minutes on placebo to 9.3 minutes on high dose, compared with an increase from 10.4 to 17.1 minutes for controls. Narcoleptics' error rate on the driving task decreased from 2.53% on placebo to 0.33% on high dose, compared with a decrease from 0.22% to 0.16% for controls. The effects of methamphetamine on nocturnal sleep were generally dose-dependent and affected sleep continuity and rapid eye movement (REM) sleep. Elimination half life was estimated to be between 15.9 and 22.0 hours. Mild side effects emerged in a dose-dependent fashion and most often involved the central nervous system and gastrointestinal tract. We concluded that methamphetamine caused a dose-dependent decrease in daytime sleep tendency and improvement in performance in both narcoleptics and controls. Methamphetamine at doses of 40-60 mg allowed narcoleptics to function at levels comparable to those of unmedicated controls.

Adult↗

PubMed1996

[A case of amotivational syndrome as a residual symptom after methamphetamine abuse].

We had a case of psychiatric evidence who was homeless and exhibited severe abulia and autism on detention for assault and battery. It was thought that his past history of chronic methamphetamine abuse and his familial history played some part in his showing such symptoms. His mother was alcohol dependent. He was an ACOA (adult child of alcoholics), which might have led to his chronic abuse of methamphetamine. On the other hand, it is well-known fact that the amotivational syndrome induced by marijuana abuse is typified by a diminution of ambition, productivity, and motivation. However, it has been contended that amotivational syndrome is induced not only by marijuana but also by amphetamine and its analogs, cocaine and volatile solvents. Since we positively support this view, we diagnosed the case as amotivational syndrome after long-term methamphetamine abuse. This was also a rare criminal case of amotivational state without hallucinations and delusions after methamphetamine abuse. We suggested that the crime committed in this case was closely related to crime induced by economic problems in residual states of schizophrenic offenders. This could be a case of both ACOA and methamphetamine dependence. There were unresolved alcohol- and drug-related problems in this case. Therefore, careful early intervention in a crisis, cooperation with the authorities and the institutions concerned, and comprehensive rehabilitation should be employed to resolve such alcohol- and drug-related problems.

Adult↗

PubMed2006

Short-term treatment of cocaine and/or methamphetamine abuse with vigabatrin: ocular safety pilot results.

OBJECTIVE: To evaluate the ocular safety of short-term use of vigabatrin to treat cocaine and/or methamphetamine addiction. METHODS: Individuals who were actively using cocaine and/or methamphetamine were eligible for enrollment. Enrolled subjects were scheduled for comprehensive eye examinations at the beginning and end of the study. Visual field testing was performed at baseline and 1 week, 4 weeks, 8 weeks, and 1 month or more after discontinuing vigabatrin. Twenty-eight subjects received at least 1 dose of vigabatrin; however, only 20 subjects continued beyond the initial escalating vigabatrin dose phase to the treatment phase. Of these 20 subjects, 18 completed the study with full follow-up. Visual fields were evaluated subjectively by 2 glaucoma specialists and analyzed objectively for group and individual changes in quadrant mean sensitivity. The objective analysis was also repeated for superior field quadrants after excluding the uppermost peripheral points to minimize the eyelid effect. The main outcome measures were change of visual field, visual acuity, and ocular adverse effects. RESULTS: Vigabatrin seemed to help treat cocaine and/or methamphetamine addiction. Of 18 subjects, 16 had negative test results for cocaine and methamphetamine use during the last 6 weeks of the trial. No ocular adverse events were detected. The subjective evaluation did not reveal visual field constriction in any of the 18 evaluable participants. Objective group and individual analyses for quadrant mean sensitivity did not show any change from baseline in any quadrant. No changes in visual acuity were noted. CONCLUSIONS: In this short-term pilot study, vigabatrin seemed to help treat cocaine and/or methamphetamine abuse. There was no evidence of ocular or visual field adverse effects.

Adult↗

PubMed2005

Effective injection in pulsed splitless mode for impurity profiling of methamphetamine crystal by GC or GC/MS.

Gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) are commonly used for the impurity profiling of illegal drugs. For the impurity profiling of methamphetamine, it is very important to obtain information about impurities related to the manufacturing route and the precursor chemicals [B. Remberg, A.H. Stead, Drug characterization/impurity profiling, with special focus on methamphetamine: recent work of the United Nations International Drug Control Programme, Bull. Narcotics LI (1999) 97-117 ]. There are many artifact impurities arising from the preparation of samples and conditions of GC. Moreover, some impurities pose a barrier to the statistical processing of methamphetamine profiling. We investigated capillary GC analysis using pulsed splitless (PS/L) injection to minimize the thermal decomposition of impurities at the injection port and improve the transfer of samples into the column. We confirmed that the optimal conditions of PS/L-mode are 230 degrees C (injection temperature), 50 psi (pulsed pressure) and 1.1 min (pulsed time) for the methamphetamine profiling. Based on the impurity profiles of 48 methamphetamine crystals in PS/L-mode, we can achieve very easy handling and obtained, good results.

Journal Article↗

PubMed2005

Prefrontal grey-matter changes in short-term and long-term abstinent methamphetamine abusers.

Authors explored grey-matter density in 29 methamphetamine abusers and 20 healthy comparison subjects using voxel-based morphometry. Grey-matter density changes and performances on the Wisconsin Card Sorting test (WCST) were also compared between 11 short-term (<6 months) and 18 long-term (>or=6 months) abstinent methamphetamine abusers. Methamphetamine abusers had lower grey-matter density in the right middle frontal cortex (corrected p<0.05) and more total errors in the WCST (p<0.01) relative to healthy comparison subjects. Grey-matter density decrease in the right middle frontal cortex correlated with total errors in the WCST in methamphetamine abusers (r=-0.45). Long-term abstinent abusers had significantly less right middle frontal grey-matter density decrease (p<0.01) and total errors in the WCST (p<0.01) than short-term abstinent abusers, but more than the healthy comparison subjects. We report that methamphetamine abusers have prefrontal grey-matter deficit, which may, in part, recover with long-term abstinence.

Adult↗

PubMed2006

Catecholamine response to methamphetamine is related to glucocorticoid levels but not to pleasurable subjective response.

INTRODUCTION: Corticosteroids may modulate addiction. We previously described subjective, physiological, and endocrine effects of 0.5 mg/kg of intravenous methamphetamine after augmenting cortisol level with hydrocortisone or blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone in a double-blind, balanced crossover study. Although the pharmacologic manipulations produced the expected hormonal changes, pleasurable subjective effects of methamphetamine were unchanged. Metyrapone was followed by frequent premature ventricular complexes (PVCs) in two subjects during methamphetamine administration. In order to better understand these results, we examined changes in two plasma catecholamine metabolites, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and their relationship to the previously reported hormonal changes and physiological and subjective responses. METHODS: Plasma from 10 methamphetamine subjects from the earlier study was assayed for HVA and MHPG by high performance liquid chromatography. RESULTS: HVA levels were greater after hydrocortisone or metyrapone pretreatment compared to placebo, and MHPG levels were greater after metyrapone pretreatment. Hydrocortisone pretreatment diminished HVA and MHPG increases after methamphetamine (perhaps explaining the lack of expected increase in pleasurable effects), but metyrapone did not. HVA and MHPG concentrations were not correlated with pleasurable drug effects but were inversely related to reports of "Bad Drug Effect." Increases in MHPG and DHEA concentrations were positively correlated. Metyrapone pre-treated subjects with PVCs had lower HVA and MHPG concentrations. CONCLUSION: Raising cortisol concentration and blocking cortisol synthesis did not produce opposite effects, perhaps because of metyrapone's effect on the hypothalamic-pituitary-adrenal axis, its stress-like effects, and its effects on neurosteroids.

Adult↗

PubMed2003

Methamphetamine abuse as a barrier to HIV medication adherence among gay and bisexual men.

Medication adherence among persons with HIV infection is important not only because of the effect of non-adherence on an individual's health but also because non-adherence can lead to medication-resistant viral strains. However, adherence to HIV medications is difficult due to complex dosing regimens and side effects. This paper is a qualitative analysis of HIV medication adherence among gay and bisexual methamphetamine-abusing men enrolled in an outpatient drug treatment research project. As part of an open-ended, semi-structured interview, 23 HIV-infected men discussed the effects of their methamphetamine use on their medication adherence. Substance-use barriers to adherence were coded into two main themes: (1) planned non-adherence and (2) unplanned non-adherence. Planned non-adherence was a strategy for coping with demanding HIV medication schedules, or was linked to sexual behaviours while using methamphetamine or to fears of interaction effects from mixing methamphetamine with HIV medications. Participants did not define their medication regimen adjustments as non-adherence but as a way to achieve a sense of control over their lives. Unplanned non-adherence was linked to methamphetamine-related disruptions in food and sleep schedules. Findings are helpful in designing culturally specific HIV medication adherence interventions for this population.

Adult↗

PubMed2005

Emerging research on methamphetamine.

PURPOSE OF REVIEW: To describe and review the literature published on methamphetamine in 2003-2004, with a particular focus on patterns of use, its effects on the user and society, and progress being made towards effective treatment strategies. RECENT FINDINGS: The methamphetamine epidemic continues to grow, dominating drug use trends in many parts of the world, and signifying an increasing need for effective treatment. In addition to the already-documented physical effects of the drug, preliminary evidence suggests methamphetamine dependence may cause long-term neuronal damage. Recently abstinent users have been found to do poorly on neurocognitive tests of attention and motor skills, both factors that can adversely affect treatment outcomes. Methamphetamine use is also implicated in aggression and violence and there are increasing presentations to emergency rooms. It also affects the developing fetus, as well as children and adults who are exposed to toxic chemicals at laboratory sites. Outpatient programs, such as the Matrix Model, show improved in-treatment performance. Case management was found to be an effective intervention. Agonist-type pharmacotherapy in combination with quality behavioral therapy should produce benefit and a reduction in risks caused by stimulant abuse. SUMMARY: The increasing evidence that methamphetamine has adverse effects on the human brain indicates the pressing need for effective prevention and treatment approaches. There is a need to take these findings, particularly those that involve cognitive deficits, into consideration in current treatment programs and when developing new treatments.

Journal Article↗

PubMed2004

Distribution and optical purity of methamphetamine found in toxic concentration in a civil aviation accident pilot fatality.

Toxicological evaluation of postmortem samples collected from a pilot involved in a unique fatal civil aircraft accident is described in this paper. A one-occupant airplane was substantially damaged upon colliding with terrain in poor visibility. Remains of the pilot were found outside the aircraft. Pathological examination revealed multiple blunt force injuries and vascular congestion. The fluorescence polarization immunoassay disclosed 8.0 microg/mL amphetamines in urine. Gas chromatographic/mass spectrometric analyses determined the presence of methamphetamine (1.13 microg/mL in blood and 59.2 microg/mL in urine) and amphetamine (0.022 microg/mL in blood and 1.50 microg/mL in urine). Methamphetamine was distributed throughout the body, including the brain. The amount of methamphetamine in gastric contents was 575-fold higher than that of amphetamine. The (+)- and (-)-forms of methamphetamine were present in equal proportions in gastric contents. The methamphetamine concentration found in blood was in the range sufficient to produce toxic effects, causing performance impairment.

Accidents, Aviation↗

PubMed1963

Behavioral effects of caffeine, methamphetamine, and methylphenidate in the rat.

It was possible to distinguish three closely-related psychomotor stimulants, caffeine, methamphetamine, and methylphenidate, by means of two operant behavior procedures, fixed interval and fixed number. Under the fixed interval procedure, the percentage change in the number of R(B)s per reinforcement was significantly smaller with caffeine than with methamphetamine or methylphenidate (p < .001). Under the fixed number procedure, the percentage change was significantly smaller with methamphetamine than with caffeine or methylphenidate (p < .001). Thus, methylphenidate had a methamphetamine-like effect under fixed interval and a caffeine-like effect under fixed number.

Animals↗

PubMed2004

Toll of methamphetamine on the trauma system.

HYPOTHESIS: Methamphetamine use affects length of hospital stay in the minimally injured patient. DESIGN: Case series. SETTING: The only tertiary trauma center serving Hawaii. PATIENTS: Trauma patients examined during a 12-month period with an Injury Severity Score of 1 to 5 and an age of 18 to 55 years undergoing urine toxicology screen for suspected suicide attempt or altered sensorium. MAIN OUTCOME MEASURES: Presence or absence of amphetamine or methamphetamine on urine toxicology screen, intention of injury, hospital admission rate, length of stay, and hospital charges. RESULTS: During the study period, 1650 trauma patients were examined, with 544 meeting study criteria. Urine toxicology screens were performed in 212 patients, with 57 positive and 155 negative for amphetamine or methamphetamine. There was no difference in sex (77% vs 73% male; P =.53), Injury Severity Score (3.2 for both groups), or total number of computed tomographic scans performed (mean +/- SEM, 3.0 +/- 0.3 vs 4.0 +/- 0.3; P =.07). Patients in the positive group were more likely to have intentional self-inflicted injury or intentional assaults than patients in the negative group (37% vs 22%; P =.04). The positive group was older than the negative group (33.6 +/- 1.3 vs 29.9 +/- 0.8 years; P =.02), had a significantly longer hospital stay (2.7 +/- 0.4 vs 1.7 +/- 0.1 days; P =.003), had significantly higher hospital charges (15 617 dollars +/- 1866 dollars vs 11 600 dollars +/- 648 dollars; P =.01), and was more likely admitted to the hospital (91% vs 70%; P =.001) despite the low Injury Severity Score. CONCLUSION: Methamphetamine use results in trauma center resource utilization out of proportion to injury severity.

Adolescent↗

PubMed1999

Enantiomer-specific high-performance liquid chromatography with fluorescence detection of methamphetamines in abusers' hair and urine.

Enantiomer-specific high-performance liquid chromatography with fluorescence detection using 4-(4,5-diphenyl-1H-imidazol-2-yl)-benzoyl chloride as a fluorescence labeling reagent was applied to determine methamphetamine and its metabolites in abusers' hair and urine. Hair samples were segmentally analyzed based on 1 cm long segments. In four hair samples, only the S(+)-enantiomers of methamphetamine and its N-demethylated metabolite, S(+)-amphetamine were detected. Satisfactory correlation (r = 0.901) between the results of high-performance liquid chromatography-fluorescence and those of gas chromatography-nitrogen phosphorous detection was obtained (n = 19). In an abuser's urine sample, the S(+)- and R(-)-enantiomers of methamphetamine, amphetamine and para-hydroxymethamphetamine were detected. The degree of N-demethylation of S(+)-methamphetamine into the corresponding metabolite of amphetamine was significantly higher than that of the R(-)-enantiomer.

Chromatography, Gas↗

PubMed1999

Stereoselective screening for and confirmation of urinary enantiomers of amphetamine, methamphetamine, designer drugs, methadone and selected metabolites by capillary electrophoresis.

Data presented in this paper demonstrate that a competitive binding, electrokinetic capillary-based immunoassay previously used for screening of urinary amphetamine and analogs cannot be employed to distinguish between the enantiomers of amphetamine and methamphetamine. However, capillary zone electrophoresis with a pH 2.5 buffer containing (2-hydroxypropyl)-beta-cyclodextrin as chiral selector is shown to permit the enantioselective analysis of urinary extracts containing methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (Ecstasy) and other designer drugs, and methadone together with its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. In that approach, enantiomer identification is based upon comparison of extracted polychrome UV absorption data and electropherograms obtained by rerunning of spiked extracts with spectra and electropherograms monitored after extraction of fortified blank urine. The suitability of the described chiral electrokinetic capillary method for drug screening and confirmation is demonstrated via analysis of unhydrolyzed quality control urines containing a variety of drugs of abuse. Furthermore, in a urine of a patient under selegiline pharmacotherapy, the presence of the R-(-)-enantiomers of methamphetamine and amphetamine could be unambiguously identified. Direct intake of an R-enantiomer or ingestion of drugs that metabolize to the R-enantiomers can be distinguished from the intake of S-(+)-enantiomers (drug abuse) or prescribed drugs that metabolize to the S-enantiomers of methamphetamine and amphetamine. The described approach is simple, reproducible, inexpensive and reliable (free of interferences of other major basic drugs that are frequently found in toxicological urines) and could thus be used for screening for and confirmation of urinary enantiomers in a routine laboratory.

Amphetamine↗

PubMed1993

In utero methamphetamine effects: I. Behavior and monoamine uptake sites in adult offspring.

Chronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a regional increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open-field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine.

Animals↗

PubMed1997

Binding of methamphetamine to serum albumin in various species in vitro.

While drugs from experimental animals provide very important information, it is also true that data differ from species to species, and that data from experimental animals cannot be applied directly to humans. The binding parameters of serum albumin from various animal species and methamphetamine were investigated in vitro by the Scatchard method. The Scatchard plots for the binding of serum albumin and methamphetamine were classified into three patterns: straight lines for human and rat serum albumin; downwardly convex curves for bovine and rabbit serum albumin; and upwardly convex curves for horse, mouse and chicken serum albumin. Hill coefficients were calculated for binding in which the Scatchard plots were upwardly convex curves and for guinea pig serum albumin. The results suggested the existence of positive cooperativity between the methamphetamine binding sites on serum albumin from the horse, mouse, chicken and guinea pig. Furthermore, the process of methamphetamine binding to human serum albumin appears to differ from the process for all experimental animals except the rat, and there are also differences between the binding processes in the various experimental animals.

Animals↗

PubMed1986

Forensic toxicologic analysis of methamphetamine and amphetamine in body materials by gas chromatography/mass spectrometry.

Qualitative and quantitative analysis of methamphetamine and amphetamine in biologic materials was carried out by gas chromatography/mass spectrometry. A deuterium-labeled methamphetamine was employed as an internal standard with a detection limit of 50 pg and absolute stability and reproducibility. Blood was found to be the best material for estimation of the toxicity of the stimulant drug. It can be replaced by muscle which contains methamphetamine concentrations close to those of blood. The authors' classification of the toxic blood levels of methamphetamine from therapeutic to fatal doses was confirmed by additional data obtained from new case studies.

Amphetamine↗

PubMed1976

Methamphetamine self-administration in the cat.

A procedure for studing intravenous drug self-administration in the cat is described. Ten cats were given 24-h access to methamphetamine reinforcement (0.04 mg/kg/inj). The subjects maintained a significantly higher response rate for drug reinforcement than for saline. The pattern of self-administration over days alternated between periods of high and low drug intake. Six additional cats were used to study the effect of dose per injection on methamphetamine self-administration under conditions of limited access. When methamphetamine was subtituted at various doses per infusion in animals maintained on cocaine reinforcement, response rate was shown to be an inverted U-shaped function of dose. These studies demonstrate that methamphetamine is a reinforcer in the cat and its patterns of intake under conditions of 24-h and limited access resemble other species.

Animals↗

PubMed1976

Effect of cortisone, aldosterone and nialamide on "amphetamine stereotypies" and brain methamphetamine levels of adrenalectomized rats.

Cortisone, aldosterone or nialamide was administered to adrenalectomized or sham-operated rats for 7 days, and methamphetamine was injected 24 hrs after the last injection of these compounds. Stereotyped head movement and licking activity were scored 5 min, 30 min and 60 min after methamphetamine injection and, in parallel brain methamphetamine levels in similarly treated rats were measured 5 min, 30 min and 60 min after the methamphetamine injection. Adrenalectomy depressed stereotyped head movements but enhanced the brain amphetamine accumulation. Nialamide but not the hormones further increased the amphetamine accumulation in adrenalectomized rats. No drugs had any effect on the amphetamine-induced head movement suppressed by adrenalectomy.

Adrenal Glands↗