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PubMed2000

Methamphetamine and HIV-1: potential interactions and the use of the FIV/cat model.

The interaction of methamphetamine with human immunodeficiency virus (HIV), the aetiologic agent of Acquired Immune Deficiency Syndrome (AIDS), has not been thoroughly investigated. However, increasingly, a larger proportion of HIV infected individuals acquire the virus through methamphetamine use or are exposed to this drug during their disease course. In certain populations, there is a convergence of methamphetamine use and HIV-1 infection; yet our understanding of the potential effects that simultaneous exposure to these two agents have on disease progression is extremely limited. Studying the interactions between methamphetamine and lentivirus in people is difficult. To thoroughly understand methamphetamine's effects on lentivirus disease progression, an animal model that is both clinically relevant and easily manipulated is essential. In this report, we identified potential problems with methamphetamine abuse in individuals with a concurrent HIV-1 infection, described the Feline Immunodeficiency Virus (FIV)/cat model for HIV-1, and reported our early findings using this modelling system to study the interaction of methamphetamine and lentivirus infections.

Amphetamine-Related Disorders↗

PubMed2005

Methamphetamine use in nonurban and urban drug court clients.

Population-based surveys suggest that methamphetamine use and abuse may be rising in the United States. However, little is known about methamphetamine use in eastern sections of the United States, particularly nonurban areas. The purpose of the present study was (a) to explore reported methamphetamine use and its correlates among Kentucky drug court clients and(b) to determine whether differences exist between methamphetamine users by drug court location. Of the 500 drug court clients surveyed, approximately 32% n=161) reported lifetime methamphetamine use. Methamphetamine users and nonusers differed in their drug-use profiles, self-reported criminal history, and number of criminal offenses. Nonurban and urban methamphetamine users differed in their drug-use profiles, psychological functioning, self-reported criminal history, and number of criminal offenses. These results suggest that differences exist between these populations and clinicians, and criminal justice officials may need to consider these differences when planning treatment and rehabilitation strategies.

Adolescent↗

PubMed2004

Fos expression associated with the discriminative stimulus effects of methamphetamine in rats.

Methamphetamine, a psychostimulant drug, produces both acute psychomotor stimulation and long-lasting behavioral effects including addiction and psychosis. To identify anatomical substrates for the discriminative stimulus effects of methamphetamine in rats, we examined the drug discrimination-associated c-Fos expression in the brains of rats that were trained to discriminate methamphetamine from saline under a two-lever fixed ratio (FR-20) schedule of food reinforcement. c-Fos expression in the brains of rats trained to discriminate methamphetamine from saline was significantly increased in the nucleus accumbens (NAc) and the ventral tegmental area (VTA) as compared with the expression in the control rats that were maintained under the FR-20 schedule, but no alternation was observed in other areas including the cerebral cortex, caudate putamen, substantia nigra, hippocampus, amygdala, and habenulla. Methamphetamine treatment in the trained rats caused a significant increase in c-Fos expression in the VTA, and a decrease in the NAc core, as compared to saline treatment. However, c-Fos expression in the NAc and VTA of rats that received chronic intermittent methamphetamine administration without discrimination training, did not differ from the expression in saline-treatment animals. These results suggest that the VTA and the NAc play an important role in the discriminative stimulus effects of methamphetamine.

Animals↗

PubMed1987

Effects of quinidine and cimetidine on the methamphetamine level in the rat brain.

The drug interaction between methamphetamine and quinidine/cimetidine was investigated in terms of distribution of methamphetamine to the brain. The concentrations of methamphetamine and amphetamine in the brain after an s.c. injection of methamphetamine were determined in rats pretreated with a single oral dose of quinidine or cimetidine. Both drugs markedly enhanced the increase in the concentrations of methamphetamine and its metabolite, amphetamine. These results suggest that the recent finding of the enhancements of the behavioral effect of methamphetamine by quinidine and cimetidine is due to the increase in levels of methamphetamine and amphetamine in the brain by these pretreatment drugs.

Amphetamine↗

PubMed1997

A histopathological study of pancreatic lesions after chronic administration of methamphetamine to rats.

The effects of chronic administration of methamphetamine on pancreatic tissues were histopathologically studied in experimental models. Methamphetamine (1 ml/kg body weight/day) was subcutaneously injected into 14 five-week-old male Wistar Kyoto rats (WKY) for 12 weeks. Age and sex matched 5 WKY rats served as controls. With light microscopy, some scattered edematous lesions and moderate vacuolization were demonstrated in the pancreas of 8 of the methamphetamine treated rats. However, in 4 of the rats, severe regional hemorrhage, partial acinal cell necrosis, destruction of the acinal cells, neutrophile infiltration, interstitial vessel dilatation, interstitial edema and fatty cell invasion were observed after the injections of methamphetamine. In 2 other animals, fibrosis and cirrhosis-like lesions with destruction and degeneration of the acinal cells were observed the small vessels had a slight degeneration of the endothelial cells. In the control animals, no lesions, except for some edematous lesions were found. In all cases, there were no nesidioblastosis-like lesions or necrosis of the Langerhans's islets. In the immunohistochemical study using anti- alpha 1-chymotrypsin antibody, more positive reactive cells were demonstrated among the interstitial and inter acinal cells, both in number and degree, in the methamphetamine treated rats. In addition to the animal model, there were 4 autopsy cases of sudden death in chronic methamphetamine abusers. The autopsies demonstrated a severe acute necrotic hemorrhagic pancreatitis, with only scattered slight hemorrhaging in the brain and lungs. These findings indicate that chronic administration of methamphetamine to rats evoked significant changes in pancreatic tissues including some degeneration of the endothelial cells of the small vessels in this hypoxia-vulnerable organ.

Animals↗

PubMed1992

Plasma and urinary concentrations of methamphetamine after oral administration of famprofazone to man.

1. To obtain further evidence for the metabolic formation of methamphetamine from famprofazone in man, concentrations of methamphetamine in plasma, as well as in urine, were measured by g.l.c. In addition, intact famprofazone and famprofazone N-oxide were analysed in the urine. 2. Methamphetamine appeared in plasma 1 h after a single 100 mg dose of the drug to two male subjects, and the concentration maintained between 24 and 44 ng/ml over 2-12 h, declining to 10 ng/ml and an undetectable level respectively after 24 h. 3. Total urinary excretion of methamphetamine over 72 h was 1.9 mg for a 25 mg dose and 2.2 mg for a 50 mg dose. After a 100 mg dose, 4.6 mg of methamphetamine was excreted over 36 h. Neither intact famprofazone nor famprofazone N-oxide were detected when the urine samples after the 100 mg dose were examined. 4. The results provide further evidence that methamphetamine is a bona fide human metabolite of famprofazone and suggest that at least 20% dose may be broken down via the pathways leading to the formation of methamphetamine. This could have significant clinical implications as the result of pharmacological activity of this metabolite.

Administration, Oral↗

PubMed2001

SPME/GC-MS characterization of volatiles associated with methamphetamine: toward the development of a pseudomethamphetamine training material.

The headspace profiles of eleven methamphetamine (MA) samples have been analyzed using solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS). Nine of the eleven are illicit MA seizures from the Southwest U.S. border. One sample is methamphetamine base synthesized in the Drug Enforcement Administration (DEA) Southwest Laboratory, and the remaining sample is pharmaceutical-grade methamphetamine hydrochloride that is used to make training aids for drug detecting canines. In addition. volatiles associated with 1-phenyl-2-propanone (P2P), a methamphetamine precursor, have been identified for comparison with those found in methamphetamine seizure and the two reference samples. Eighty-seven different compounds were identified from all the samples, not including simple hydrocarbons and aldehydes. Only seven occur consistently in all seizure samples, and these are: acetic acid, benzaldehyde, acetophenone, P2P, 1-phenyl-1,2-propanedione (P12P), 3-phenyl-3-buten-2-one, 1-chloro-1-phenyl-2-propanone. Dimethyl sulfone, a common cutting agent in methamphetamine. was found in six of the nine seizure materials. When the reference methamphetamine and P2P samples are included, only two compounds are common to all twelve samples, and these are benzaldehyde and P2P. As such, these two compounds are likely candidates for use in a pseudomethamphetamine (PM) formulation, and their effectiveness in eliciting a canine response is being evaluated before actual deployment.

Animals↗

PubMed2001

Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

Adult↗

PubMed1975

Effect of methamphetamine on norepinephrine metabolism in various regions of brain.

The effects of methamphetamine on tritiated and endogenous norepinephrine metabolism was examined in various regions of brain. In acute experiments, 30 minutes or 5 hours after methamphetamine i.p., 3H-norepinephrine was injected into the cisterna magna. In chronic experiments, rats were administered increasing doses of methamphetamine twice a day for 17 days, then 18 hours after the last dose of methamphetamine, 3H-norepinephrine was injected intracisternally. All rats were killed 5 minutes after the intracisternal injection and their brains removed, dissected into five parts and assayed for endogenous norepinephrine, 3H-norepinephrine and its metabolites. In rats treated acutely, methamphetamine caused a significant block in uptake of 3H-norepinephrine and a marked increase in the content of 3H-normetanephrine in all regions except the cortex. Five hours after methamphetamine administration, increased levels of 3H-norepinephrine occurred in the pons-medulla, whereas endogenous norepinephrine content tended to decrease in most regions. In rats treated chronically, enhanced accumulation of 3H-norepinephrine was also confined to the pons-medulla region, whereas endogenous levels of norepinephrine were high in the pons-medulla and low in the hypothalamus and cortex. These data suggest that chronic administration of methamphetamine affects either catecholaminergic nerve cell bodies or nerve terminals in the pons-medulla differentially, as compared to other regions studied.

Animals↗

PubMed2001

[Study of distribution and metabolism of methamphetamine in hair of guinea pig].

OBJECTIVE: To study the distribution and metabolism of methamphetamine in the hair of guinea pig. METHODS: Determination of methamphetamine and its metabolite amphetamine in hair was performed by GC/MS and GC/NPD. Concentration-time course of methamphetamine and amphetamine in hair of guinea were recorded. Relationship between hair color, administrated dose and drug concentration in hair were also discussed. RESULTS: The concentration of amphetamine is higher than the concentration of methamphetamine in the hair of guinea administrated a single dose or seven doses of methamphetamine. The concentration of methamphetamine and amphetamine were significantly related with administration dose and the incorporation rate into white and brown hair is much poorer than that of black hair. CONCLUSION: Administration methods, dose and the color of hair affect the concentration of methamphetamine and amphetamine.

Amphetamine↗

PubMed1992

Motor impairments after methamphetamine-induced neurotoxicity in the rat.

Methamphetamine is a psychomotor stimulant which, given in high doses, produces neurodegenerative changes in the dopamine and serotonin systems. This study was designed to assess motoric deficits in the rat following a high-dose regimen of methamphetamine. Long-Evans male rats received either four injections of saline or methamphetamine (12.5 mg/kg, every 2 hr), a dose sufficient to produce 45 and 36% reductions in striatal dopamine and serotonin, respectively. Before treatment, subjects were trained to perform one of the following motor tasks: one-way active avoidance, inhibitory avoidance, rotorod or the balance beam. After recovery, performance under base-line and drug challenge conditions revealed that methamphetamine treatment caused significant deficits in active avoidance performance (24% increase in response latency) and balance beam performance (2- to 3-fold increase in footfalls), but had no effect on inhibitory avoidance or rotorod performance. Administration of l-dopa (100 mg/kg) significantly improved the methamphetamine-treated subjects' performance on the balance beam, but had no effect on the control subjects' performance. The methamphetamine-treated subjects exhibited a significant decrease in sensitivity to the effects of fenfluramine in comparison to the controls on both the rotorod and active avoidance tasks. We conclude that high-dose methamphetamine treatment produces long-lasting motor deficits associated with chronic reductions of striatal dopamine and serotonin. These data and the utility of the motor tasks are discussed in reference to a laboratory model of Parkinson's disease.

Animals↗

PubMed2003

Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice.

Ovarian hormones were well documented to modulate the dopamine release in the central dopaminergic systems. The dopamine-releasing effects in the nucleus accumbens, a major target of the mesolimbicortical dopaminergic system, were closely associated with the reinforcing effects of two psychomotor stimulants, cocaine and methamphetamine. This study aimed to examine the sex differences in the cocaine- and methamphetamine-reinforcing behavior, conditioned place preference. In addition, the modulating effects of estradiol and progesterone on methamphetamine-induced conditioned place preference were investigated in both sexes of adult gonadectomized mice. There was no sex difference in the sensitivity to the cocaine (5 mg/kg)-induced conditioned place preference. However, female mice exhibited a more potent methamphetamine (1 mg/kg)-induced conditioned place preference than did male mice. Moreover, pretreatment with estradiol for two consecutive days before the beginning of the conditioning and throughout the four daily conditionings (0.47 microg/day for totally six days) effectively facilitated methamphetamine-induced conditioned place preference in gonadectomized female mice, but not in gonadectomized male mice. Progesterone, under a similar treatment regimen (0.47 microg/day for six consecutive days), did not alter the methamphetamine-induced conditioned place preference in either sex of gonadectomized mice. Taken together, we conclude that the facilitating effects of estradiol on methamphetamine-induced conditioned place preference could be sex-dependent with an eminent sensitivity associated with the adult female mice.

Animals↗

PubMed2004

Methamphetamine abuse during pregnancy and its health impact on neonates born at Siriraj Hospital, Bangkok, Thailand.

To ascertain the impact of intrauterine methamphetamine exposure on the overall health of newborn infants at Siriraj Hospital, Bangkok, Thailand, birth records of somatic growth parameters and neonatal withdrawal symptoms of 47 infants born to methamphetamine-abusing women during January 2001 to December 2001 were compared to 49 newborns whose mothers did not use methamphetamines during pregnancy. The data on somatic growth was analyzed using linear regression and multiple linear regression. The association between methamphetamine use and withdrawal symptoms was analyzed using the chi-square. Home visitation and maternal interview records were reviewed in order to assess for child-rearing attitude, and psychosocial parameters. Infants of methamphetamine-abusing mothers were found to have a significantly smaller gestational age-adjusted head circumference (regression coefficient = -1.458, p < 0.001) and birth weight (regression coefficient = -217.9, p < or = 0.001) measurements. Methamphetamine exposure was also associated with symptoms of agitation (5/47), vomiting (11/47) and tachypnea (12/47) when compared to the non-exposed group (p < 0r =0.001). Maternal interviews were conducted in 23 cases and showed that: 96% of the cases had inadequate prenatal care (<5 visits), 48% had at least one parent involved in prostitution, 39% of the mothers were unwilling to take their children home, and government or non-government support were provided in only 30% of the cases. In-utero methamphetamine exposure has been shown to adversely effect somatic growth of newborns and cause a variety of withdrawal-like symptoms. These infants are also psychosocially disadvantaged and are at greater risk for abuse and neglect.

Adolescent↗

PubMed2006

Methamphetamine: putting the brakes on speed.

In only recent history, illicit use of methamphetamine, once isolated to urban areas on the West Coast, has spread into rural areas of the Midwest and southern United States. Although past and current methamphetamine legislation has increased penalties for methamphetamine manufacturers and tightened restrictions on sales of known precursors, the problem still persists. In fact, a 2004 survey indicates that an alarming 6.2% of high school seniors have tried methamphetamine. A number of biological, genetic, and environmental factors influence children's and adolescents' paths to substance abuse. Nurses should recognize the symptoms of methamphetamine abuse, which include agitation; aggressive behavior; rapid mood swings; hypertension; tachycardia; and eventually lesion-marked skin, clinical depression, and paranoid psychosis. Treatment for methamphetamine addiction includes behavioral therapy. Research on pharmacologic therapy is lacking. Educating youth on methamphetamine prevention appears to be the best approach to curb the spreading use of this addictive and deadly drug.

Acute Disease↗

PubMed1986

[Intracerebral hemorrhage and characteristic angiographic changes associated with methamphetamine--a case report].

A case of intracerebral hemorrhage and characteristic angiographic changes associated with methamphetamine is reported. A 23-year-old woman suddenly complained of headache, nausea, vomiting and gait disturbance several minutes after intravenous injection of 30 mg of methamphetamine. She was admitted with consciousness disturbance, aphasia and right hemiparesis 26 hours after the onset. CT scan revealed subcortical hemorrhage in the left fronto-parietal region. Left carotid angiogram showed irregular segmental arterial narrowing, "beading" of the anterior and middle cerebral arteries. Emergency craniotomy was performed and a left fronto-parietal hematoma was removed totally. Histologically, the surgical specimen showed many vessels in which included thrombi with perivascular hemorrhage. Post-operative course was uneventful. Repeat carotid angiogram 4 months after the operation revealed normal anterior and middle cerebral arteries. We discussed about associations between the abuse of methamphetamine and the occurrence of intracranial hemorrhage and characteristic angiographic changes. As far as we know, there were 23 reports in an extensive review of the literature on intracranial hemorrhage associated with methamphetamine abuse. In the present case "beading" of the intracranial vessels may be related to angiitis induced by methamphetamine. Both the presence of arterial inflammation and increased blood pressure caused by sympathomimetic action of methamphetamine are probably the important factors in the occurrence of intracranial hemorrhage associated with methamphetamine.

Adult↗

PubMed1986

[Effects of repeated administration of bromocriptine on ambulatory activity in mice, and changes in methamphetamine sensitivity in bromocriptine-experienced mice].

Effects of repeated administration of bromocriptine, a long-acting dopamine agonist, as well as interaction between bromocriptine and methamphetamine were investigated by mean of ambulatory activity in mice. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 6 and 3 hr after administration of bromocriptine and methamphetamine, respectively. The repeated 5 times administration of bromocriptine and of methamphetamine was at intervals of 7 days and of 3-4 days, respectively. Bromocriptine tended to suppress the activity at low doses (1 and 2mg/kg, ip), but increased the activity at high doses (8 and 16 mg/kg, ip), showing biphasic effects depending on the doses administered. Both the ambulation-suppressing and -increasing effects of bromocriptine were enhanced when the drug was repeatedly administered. The mice that experienced the repeated administration of low doses and high doses of bromocriptine exhibited a decrease and an increase, respectively, in the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, sc). Repeated administration of methamphetamine (2 mg/kg, sc) elicited an increase in sensitivity not only to methamphetamine itself, showing reverse tolerance, but also to high doses of bromocriptine, showing cross reverse tolerance. However, the reverse tolerance to methamphetamine, once produced, was not affected by the repeated administration of low doses of bromocriptine.

Animals↗

PubMed1983

[Effect of methamphetamine on morphine preference].

The effect of methamphetamine on preference for morphine was studied in rats by the drug-admixed food (DAF) method. The preference rates for morphine-admixed food gradually increased by the repetition of choice and forced trials and then became stable at the level of 70%. On the other hand, the preference rates for morphine-admixed food combined with methamphetamine did not so increase compared with the case of morphine alone. From the taste aversion test, it was assumed that combination of morphine and methamphetamine did not enhance taste aversion, although methamphetamine suppressed development of preference for morphine. In the case of combination of morphine and cocaine or caffeine, preference rates for these drugs increased like the case of morphine. This result indicated that the suppression of the preference for morphine which was induced by methamphetamine was not produced by the general effect of CNS stimulants. We found that methamphetamine suppressed the development of the preference for morphine. These findings suggest that the suppression resulted from neither taste aversion nor the general effect of CNS stimulants. Furthermore, acute toxicity and other effects were enhanced by the combination of morphine and methamphetamine, and it might participate with the suppression.

Animals↗

PubMed1994

[Clinical problems of alcoholics with a history of methamphetamine abuse].

The authors studied the clinical problems of alcoholics with a history of methamphetamine abuse as compared with alcoholics with no history. The samples were in- and out-patients of Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital, from January to December 1992. This study covered 26 alcoholics who had abused methamphetamine from 1 to 40 years before, with an average age at admission was 43.5 years. This compared with a 50.4 year average for 89 alcoholics who had no history of methamphetamine abuse. Hepatitis C antibodies (HCVAb) were significantly more commonly observed in ex-methamphetamine abusers than in non-abusers (73.1% vs. 18.0%). Hepatitis B antigens (HBsAg) were no more common among abusers than non-abusers (0% vs. 2.2%). Blood transfusion history tended to be greater in ex-methamphetamine abusers than non-abusers (38.5% vs. 29.2%) but the difference did not reach conventional levels of statistical significance. Ex-abusers often wore tattoos (23.1%) whereas none of the non-abusers did, a significant difference. Significantly more ex-methamphetamine abusers were diagnosed as suffering from alcoholic hallucinosis than non-abusers (42.3% vs. 7.9%). As more ex-methamphetamine abusers than non-abusers were living alone (61.5% vs. 31.5%), were on welfare (61.5% vs. 23.8%), and living in skid-row areas (15.4% vs. 5.6%), the authors concluded that their living conditions were unstable.

Adult↗