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PubMed2006

Methamphetamine abuse: a perfect storm of complications.

Previously restricted primarily to Hawaii and California, methamphetamine abuse has reached epidemic proportions throughout the United States during the past decade, specifically in rural and semirural areas. Particular characteristics of methamphetamine production and use create conditions for a "perfect storm" of medical and social complications. Unlike imported recreational drugs such as heroin and cocaine, methamphetamine can be manufactured locally from commonly available household ingredients according to simple recipes readily available on the Internet. Methamphetamine users and producers are frequently one and the same, resulting in both physical and environmental consequences. Users experience emergent, acute, subacute, and chronic injuries to neurologic, cardiac, pulmonary, dental, and other systems. Producers can sustain life-threatening injuries in the frequent fires and explosions that result when volatile chemicals are combined. Partners and children of producers, as well as unsuspecting first responders to a crisis, are exposed to toxic by-products of methamphetamine manufacture that contaminate the places that serve simultaneously as "lab" and home. From the vantage point of a local emergency department, this article reviews the range of medical and social consequences that radiate from a single hypothetical methamphetamine-associated incident.

Adult↗

PubMed1999

Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity.

Methamphetamine neurotoxicity has been demonstrated in rodents and nonhuman primates. These neurotoxic effects may be associated with mechanisms involved in oxidative stress and the activation of immediate early genes (IEG). It is not clear, however, whether these IEG responses are involved in a methamphetamine-induced toxic cascade or in protective mechanisms against the deleterious effects of the drug. As a first step toward clarifying this issue further, the present study was thus undertaken to assess the toxic effects of methamphetamine in heterozygous and homozygous c-fos knock-out as well as wild-type mice. Administration of methamphetamine caused significant reduction in [(125)I]RTI-121-labeled dopamine uptake sites, dopamine transporter protein, and tyrosine hydroxylase-like immunohistochemistry in the striata of wild-type mice. These decreases were significantly exacerbated in heterozygous and homozygous c-fos knock-out mice, with the homozygous showing greater loss of striatal dopaminergic markers. Moreover, in comparison with wild-type animals, both genotypes of c-fos knock-out mice showed more DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled nondopaminergic cells in their cortices and striata. In contrast, wild-type mice treated with methamphetamine demonstrated a greater number of glial fibrillary acidic protein-positive cells than did c-fos knock-out mice. These data suggest that c-fos induction in response to toxic doses of methamphetamine might be involved in protective mechanisms against this drug-induced neurotoxicity.

Animals↗

PubMed2000

Methamphetamine overdose and fatality : 2 cases report.

Methamphetamine abuse is an important problem in Thailand. The number of addicts and abusers is increasing. Abusers usually use speed pills by oral ingestion or inhalation. The dose used is about 5-60 mg of methamphetamine while the lethal dose reported is 200 mg. Death due to methamphetamine toxicity is uncommon. In this paper, we report two cases of methamphetamine fatalities. Both cases were drug dealers. They swallowed a handful of methamphetamine tablets while being arrested. The autopsy revealed nonspecific findings. Using thin layer chromatography technique, methamphetamine was detected in the urine, blood, stomach and liver of the corpses. This circumstance has been reported elsewhere and might be increased in Thailand as more speed pills are circulated in illegal markets.

Adult↗

PubMed2002

Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.

The role of the histaminergic system in the discriminative stimulus effects of cocaine and methamphetamine was examined in rats trained to discriminate between saline and cocaine (10 mg/kg) or methamphetamine (1.0 mg/kg). L-histidine (400 mg/kg), a precursor of histamine, significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. Previous studies have revealed the existence of several histamine receptor types, H1-, H2-, and H3-receptors. These enhancing effects of L-histidine on the discriminative stimulus effects of cocaine and methamphetamine were attenuated by 5.0 mg/kg of pyrilamine (an H1-receptor antagonist), but not by 1.0 mg/kg of zolantidine (an H2-receptor antagonist), suggesting that these enhancing effects of L-histidine were mediated through the activation of H1-receptors. Thioperamide (7.5 mg/kg), an H3-receptor antagonist, also significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. However, neither pyrilamine nor zolantidine affected the enhancing effects of thioperamide, unlike the results attained with L-histidine. Therefore our findings suggest that the histaminergic system may modify the discriminative stimulus effects of cocaine and methamphetamine mediated through H1- and H3-receptors.

Animals↗

PubMed2002

Risk behaviors of Filipino methamphetamine users in San Francisco: implications for prevention and treatment of drug use and HIV.

OBJECTIVE: This study describes the demographics, HIV risk and drug use behaviors, and psychosocial status of Filipino American methamphetamine users in the San Francisco Bay area. METHODS: Individual interviews were conducted with 83 Filipino American methamphetamine users, recruited through snowball sampling methods. A structured survey questionnaire included measures of drug use behaviors, HIV-related sexual behaviors, psychosocial factors, and demographics. RESULTS: Filipino methamphetamine users tended to be male, to have low levels of perceived personal control in their lives, and to report low levels of shame about their drug use. Methamphetamine use was strongly associated with HIV-related risk behaviors. Frequent methamphetamine users tended to engage in drug use before or during sex and to use condoms infrequently. Commercial sex activity was associated with frequency of methamphetamine use. About one-third of the study participants had never been tested for HIV. CONCLUSION: HIV/STD and drug abuse prevention programs that target Filipino Americans are needed. These programs should be tailored to meet clients' needs on the basis of gender, employment status, acculturation, and psychosocial variables that affect drug use and sexual behaviors.

Adolescent↗

PubMed2004

Cycloheximide enhances maintenance of methamphetamine-induced conditioned place preference.

Accrued evidence demonstrated the necessity of protein synthesis at acquisition, consolidation and expression stages in conditioning/learning tasks, while the underlying mechanisms of the maintenance of memory remained less explored. This study was designed to characterize the maintenance of methamphetamine-induced conditioned place preference, a drug-induced learning and memory. In addition, cycloheximide, a protein synthesis inhibitor, was used to examine the involvement of protein synthesis in the maintenance of such place preference memory. We found that the maintenance of the rapidly-established methamphetamine (2 mg/kg, i.p.) -induced conditioned place preference could be long-lasting and even over fifty days under the present protocol of extinction. Moreover, it was of interest to note the undulating expression of this conditioned place preference throughout the extinction protocol. Most importantly, as the methamphetamine-induced conditioned place preference was acquired and expressed by mice, the saline-pretreated control mice underwent numbers of intermittent extinction across a long-term retention test period, while cycloheximide-pretreated mice exhibited unaltered methamphetamine-induced conditioned place preference throughout the same retention test period. Taken together, we conclude that [1] methamphetamine-induced conditioned place preference could last for a long period of time, and such place preference memory is reluctant to extinguish even animals' repeated exposure to the previous conditioned environment at a drug-free status, and [2] blockade of protein synthesis may enhance the maintenance of the methamphetamine-induced conditioned place preference.

Animals↗

PubMed1992

Preliminary observations of the effect of methamphetamine in decomposing tissues on the development rate of Parasarcophaga ruficornis (Diptera: Sarcophagidae) and implications of this effect on the estimations of postmortem intervals.

Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of methamphetamine to study the effects of this drug on development of this species. The rabbits were given 37.5, 71.4, and 142.9 mg of methamphetamine via ear vein infusion. From Hours 30 to 60, larvae feeding on tissues from rabbits receiving 71.4 and 142.9 mg of methamphetamine developed more rapidly than larvae from the control colony and those feeding on tissues from the rabbit receiving 37.5 mg of methamphetamine. The time required for pupariation was significantly greater for colonies fed on tissues from methamphetamine-dosed rabbits than for the control. These differences were sufficient to alter postmortem interval estimates based on larval development by up to 18 h and estimates based on puparial development by up to 48 h. The presence of methamphetamine or amphetamine could not be detected in Diptera larvae in this experiment using radioimmunoassay techniques, as there was a nonspecific reaction, resulting in a false positive.

Amphetamine↗

PubMedDate not supplied

Involvement of cannabinoid CB1 and CB2 receptor activity in the development of behavioural sensitization to methamphetamine effects in mice.

OBJECTIVES: An increased behavioural response ("behavioural sensitization") to drugs of abuse occurs after repeated treatment. In the present study the possibility of cross-sensitization existence between various cannabinoid receptor ligands--CB1 agonist methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM 251 with methamphetamine was explored. METHODS: Locomotion in the open field was measured in naive mice and in those pre-treated acutely and repeatedly (for 8 days), respectively, with either vehicle or tested drugs. RESULTS: Methamphetamine produced significant sensitization to its stimulatory effect on locomotion. Methanandamide pre-treatment elicited cross-sensitization to methamphetamine effect, whereas pre-treatment with JWH 015 did not. Combined pre-treatment with methamphetamine+AM 251 suppressed sensitization to methamphetamine. CONCLUSIONS: These results suggest that the activity of the endocannabinoid system is involved in the neuronal circuitry underlying the development of sensitization to methamphetamine.

Animals↗

PubMed1991

Cardiomyopathy associated with the smoking of crystal methamphetamine.

The smoking of crystal methamphetamine, or "ice," is a growing drug abuse problem in the United States. The toxic effects of methamphetamine smoking have not been well described. We describe two patients with cardiovascular toxic effects associated with the smoking of crystal methamphetamine. In our first patient, the use of smokeable methamphetamine was associated with the subsequent development of pulmonary edema and a dilated cardiomyopathy. In our second patient, the smoking of crystal methamphetamine likely produced diffuse vasospasm that resulted in acute myocardial infarction, cardiogenic shock, and death. The recognition of potentially lethal cardiac complications associated with the smoking of crystal methamphetamine is of extreme significance and should be emphasized to potential abusers of this drug.

Adult↗

PubMed1991

Disposition and pharmacodynamics of methamphetamine in pregnant sheep.

To determine the placental transfer of methamphetamine, its subsequent fetal disposition, and its hemodynamic effects, we administered methamphetamine intravenously to 15 pregnant ewes 3 days after placement of maternal and fetal vascular catheters. Methamphetamine crossed the placenta within 30 seconds of its administration. Although the ewes had higher peak concentrations, the fetuses' longer elimination half-life ultimately led to higher fetal than maternal methamphetamine concentrations. The ratio of fetal tissue to plasma drug concentration 2 hours after administration was highest in the lung, followed by the placenta, kidney, intestine, liver, brain, and heart. Methamphetamine caused a 54% to 63% rise in maternal blood pressure, a 20% to 37% increase in fetal blood pressure, and a drop in fetal oxyhemoglobin saturation and arterial pH. We conclude that methamphetamine, in doses at or below what is commonly abused, has effects that could be detrimental to the health of the mother and her fetus.

Animals↗

PubMed1990

Abuse of smoking methamphetamine mixed with tobacco: II. The formation mechanism of pyrolysis products.

The pyrolysis products of smoking methamphetamine mixed with tobacco were determined by gas chromatography (GC) and GC/mass spectrometry (GC/MS) methods. The mainstream smoke contained methamphetamine (14.5% of the initial methamphetamine), phenylacetone (3.1%). N-cyanomethylmethamphetamine (1.9%), trans-beta-methylstyrene (1.7%), N-formylmethamphetamine (1.5%), and other products (each less than 1%). The amount of each pyrolysis product in the sidestream smoke was less than that in the mainstream smoke by a factor of over 5, except for methamphetamine (10.5%) and N-formylmethamphetamine (1.4%). The formation mechanism of these products was investigated, by use of a pyrolyzer, from the standpoint of the material, pyrolysis temperature, and pyrolysis atmosphere. Although several products (for example, dimethylamphetamine and trans-beta-methylstyrene) were formed by thermal self-decomposition of methamphetamine alone, most of the products, except N-cyanomethylmethamphetamine, were formed chiefly by the thermal reaction of methamphetamine with cigarette components. The formation of N-cyanomethylmethamphetamine required air and a high pyrolysis temperature. Air and a high pyrolysis temperature generally accelerated the formation of the pyrolysis products.

Chromatography, Gas↗

PubMed1985

Role of dopamine in the neurotoxic effects of methamphetamine.

Multiple administrations of high doses of methamphetamine to rats cause long-term depression of both dopamine and serotonin synthesis. Coadministration of the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, antagonizes this effect of methamphetamine on both neurotransmitter systems. However, when catecholamine synthesis was maintained by the administration of L-dopa and the peripheral decarboxylase inhibitor R04-4602, alpha-methyl-p-tyrosine no longer prevented the effects of methamphetamine on either dopamine or serotonin synthesis. In addition, the administration of the specific dopamine uptake blocker, amfonelic acid, significantly attenuated the changes in the serotonin synthesizing enzyme, tryptophan hydroxylase, resulting from multiple high doses of methamphetamine. The ability of a single administration of methamphetamine to depress tryptophan hydroxylase was also dependent on catecholamine synthesis. These results suggest that dopamine plays an important role in the changes mediated by the administration of methamphetamine in both the dopaminergic and serotonergic systems.

Animals↗

PubMed1989

Effect of dopamine receptor antagonist on in vivo dopamine release induced by intrastriatal perfusion with methamphetamine in freely moving rats.

In order to investigate a regulatory role of dopamine receptors in drug-induced release in the striatum, we determined dopamine and its metabolites in dialysates simultaneously with behavioral observations following intrastriatal perfusion with methamphetamine using the transstriatal dialysis method in freely moving rats. Intrastriatal perfusion with methamphetamine (5, 50, 500 microM) for 40 min produced a marked increase in dopamine release and a slight reduction in 3,4-dihydroxyphenylacetic acid release. No significant changes in spontaneous motor activity were observed after methamphetamine at concentrations up to 500 microM. Methamphetamine-induced dopamine release was not affected by the selective D1-receptor antagonist SCH 23390 (1 microM), but was markedly enhanced by the selective D2-receptor antagonist sulpiride (1 microM), at a concentration that did not change the basal level. Intrastriatal pretreatment with kainic acid (1 micrograms into bilateral striata) slightly affected the dopamine release induced by methamphetamine. These results suggest that methamphetamine-induced dopamine release is regulated by both pre- and postsynaptic D-2 receptors in the striatum in vivo.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats.

The toxic effects of methamphetamine on dopamine and serotonergic neurons have recently been linked to the endogenous formation of 6-hydroxydopamine and 5,7-dihydroxytryptamine, respectively. It has been speculated that the ability of methamphetamine to both release dopamine and serotonin as well as to inhibit monoamine oxidase activity leads to the non-enzymatic oxidation of dopamine and serotonin to the neurotoxins. This hypothesis was evaluated by pretreating rats with high doses of an antioxidant (ascorbic acid) prior to the administration of methamphetamine. It was observed that the administration of 25.0 mg/kg of methamphetamine at 12 hour intervals for a four day period caused a long-lasting depletion of dopamine and serotonin. Pretreatment with 100.0 mg/kg of ascorbic acid 30 minutes before each methamphetamine injection significantly (but not completely) attenuated this neurotoxic action of methamphetamine. These observations are discussed in reference to animal models of Parkinson's disease.

Animals↗

PubMed1985

Combined effects of methamphetamine and morphine on ambulatory activity in mice and continuous avoidance response in rats.

Combined effects of methamphetamine and morphine were investigated by means of ambulatory activity in mice and continuous avoidance response in rats. Single administration of methamphetamine (0.5-2 mg/kg sc) or morphine (2.5-10 mg/kg sc) increased the ambulatory activity in a dose-dependent manner. The ambulation-increasing effect of methamphetamine and morphine were synergistic throughout the combined doses tested. Methamphetamine (0.13 and 0.5 mg/kg sc) produced an increase in frequency of lever-pressing and a decrease in shock rate, showing facilitation of the avoidance response, in a dose-dependent manner. Morphine tended to facilitate the avoidance response at lower doses (1.3 and 2.5 mg/kg sc), whereas, at higher doses (5 and 10 mg/kg sc), it elicited decrease in the frequency of lever-pressing and increase in the shock rate, showing suppressing of the avoidance response. The avoidance-facilitating effect of methamphetamine was attenuated by higher doses of morphine. The present results suggest that combined administration of methamphetamine and morphine shows synergistic effect on ambulatory activity in mice, and synergistic and antagonistic effects on the avoidance response in rats depending on the doses combined.

Animals↗

PubMed1984

[Motility effects of methamphetamine in morphine-tolerant mice by the DAP method].

We reported that the reverse tolerance to the effect of morphine on ambulatory activity did not develop in mice treated with morphine-admixed food. In this study, effects of repeated administration of methamphetamine on ambulatory activity were studied in mice treated with morphine-admixed food. The ambulatory activity was determined by the tilting cage method. Methamphetamine injection (1 mg/kg, s.c.) was repeated at 3 approximately 4 day intervals. The ambulatory activity was enhanced progressively when methamphetamine was repeatedly given in mice. However, the enhancing effect was not observed in mice treated with morphine-admixed food (1 mg/g food). Moreover, in a single injection experiment, the effect of the combination of methamphetamine and morphine on ambulatory activity was more potent than that of each drug. These results suggested that the reverse tolerance to methamphetamine did not develop under the condition of exposure to morphine by the DAF (drug-admixed food) method, and the developmental mechanism of reverse tolerance to methamphetamine might be similar to that of morphine.

Administration, Oral↗

PubMed1982

Inhibitory mechanism of methamphetamine in the isolated myocardium of bullfrog.

In the isolated heart of the bullfrog, both the spontaneous contractile force of the atrium and the electrically-induced contractile force of the ventricle were enhanced by the initial administration of methamphetamine. However, a second administration of the drug caused a dose-dependent negative inotropic effect. The methamphetamine-induced positive inotropic effect was reduced or abolished by either practolol or cocaine pre-treatment. The negative inotropic effect of methamphetamine was markedly attenuated after theophylline or practolol pre-treatment, but was not affected by cocaine, atropine and phentolamine pre-treatment. Methamphetamine caused a slight decrease of the adenylatecyclase activity of the intact myocardium. It also inhibited not only the cardiac excitation (contractile force and rate) but also the facilitation of adenylatecyclase activity induced by isoproterenol. A slight reduction of the methamphetamine-induced ventricular inhibition was observed by increasing the external calcium concentration; however, the inhibition was not affected by MnCl2 or verapamil pre-treatment. From these results, it is suggested that the inhibitory effect of methamphetamine on the heart may be produced through the blocking of post-synaptic beta-adrenoceptors.

Action Potentials↗

PubMed1994

125I radioimmunoassay for the dual detection of amphetamine and methamphetamine.

A radioimmunoassay that exhibits a nearly equivalent response to D-amphetamine and D-methamphetamine in urine over the assay range of 0 to 1000 ng/mL while displaying low cross-reactivity to L-amphetamine and L-methamphetamine (4.6% and 2.4%, respectively) has been developed. In addition, methylenedioxy-amphetamine (MDA) and methylenedioxymethamphetamine (MDMA) were detectable in the assay with cross-reactivity levels of > 100% and 77% respectively. Little cross-reactivity was observed with the commonly encountered over-the-counter (OTC) drugs and this cross-reactivity was further reduced by the addition of sodium periodate into the reaction mixture to oxidize the beta-hydroxylamines. The double (second) antibody assay uses 125I-radiolabeled derivatives of both D-amphetamine and D-methamphetamine as tracers in combination with two highly specific sheep antisera directed against D-amphetamine and D-methamphetamine. The assay exhibits a dose-response of approximately 90,000 dpm from 0 to 1000 ng/mL of D-amphetamine or D-methamphetamine with a minimum detectable dose for either drug of approximately 25 ng/mL. With a cut-off level of 500 ng/mL, the assay gave a positive result for 100% of the 111 clinical samples containing GC/MS confirmed (at or above the NIDA GC/MS cut-off values) levels of amphetamine and/or methamphetamine. Eighty-eight samples that screened negative in a clinical laboratory were all negative in the assay. Nineteen samples which were incorrectly identified as positive by other commercially available amphetamine assays were negative in this RIA.

Amphetamine↗