SEARCH · PubMed Health

Results for “Methamphetamine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed2006

Substitution of phenylephrine for pseudoephedrine as a nasal decongeststant. An illogical way to control methamphetamine abuse.

The aim of this review was to investigate the rationale for replacing the nasal decongestant pseudoephedrine (PDE) with phenylephrine (PE) as a means of controlling the illicit production of methamphetamine. A literature search was conducted in electronic databases and use of textbooks. Restrictions have been placed on the sale of PDE in the USA in an attempt to control the illicit production of methamphetamine. This has caused a switch from PDE to PE in many common cold and cough medicines. PE is a poor substitute for PDE as an orally administered decongestant as it is extensively metabolized in the gut and its efficacy as a decongestant is unproven. Both PDE and PE have a good safety record, but the efficacy of PDE as a nasal decongestant is supported by clinical trials. Studies in the USA indicate that restricting the sale of PDE to the public as a medicine has had little impact on the morbidity and number of arrests associated with methamphetamine abuse. Restricting the sale of PDE in order to control the illicit production of methamphetamine will deprive the public of a safe and effective nasal decongestant and force the pharmaceutical industry to replace PDE with PE, which may be an ineffective decongestant. Restrictions on sales of PDE to the public may not reduce the problems associated with methamphetamine abuse.

Amphetamine-Related Disorders↗

PubMed1995

Developmental neurotoxicity to methamphetamines.

1. To investigate the long-term changes caused by amphetamines in the developing brain, we used both an in vivo and in vitro model of chronic fetal exposure to methamphetamine and related drugs. 2. Offspring of rats, treated with either saline, 2 mg/kg twice a day (b.i.d.) or 10 mg/kg b.i.d. methamphetamine throughout gestation, were examined at 30 days of age for changes in the monoamine system of their brains. 3. At the lower dose methamphetamine was neurotoxic to specific neuronal populations, mostly serotonergic. At the higher dose, methamphetamine retained its neurotoxic properties, but also stimulated the growth of axonal terminals in specific regions as evidenced by an increase in monoamine uptake sites. The neurochemical changes at the higher dose were correlated with deficits in adult behavioural measures. 4. Corresponding in vitro drug treatments of rat neuroblastomas cells also produced a dose-related effect on cellular growth and differentiation patterns. Neurotoxic as well as stimulatory effects of methamphetamine and some related compounds were seen in culture. 5. Our in vivo and in vitro observations demonstrate neurotoxic effects of amphetamines and the remodelling of synaptic morphology in response.

Amines↗

PubMed2005

Childhood histories of attention-deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: preliminary report.

The present study examined childhood histories of attention-deficit hyperactivity disorder (ADHD) in 54 methamphetamine and 12 inhalant abusers using the Wender Utah Rating Scale. The inhalant abusers experienced initial drinking at a younger age than methamphetamine abusers (P=0.038). The Wender Utah Rating Scale score was significantly higher in the inhalant abusers than in the methamphetamine abusers (P=0.013) although 83.3% of inhalant and 55.6% of methamphetamine abusers had higher scores than the cut-off for ADHD. These findings suggest that drug abuse is associated with childhood ADHD, and that inhalant abusers have a higher incidence of childhood ADHD than methamphetamine abusers.

Adolescent↗

PubMed2005

Gene transfer of GLT-1, a glutamate transporter, into the nucleus accumbens shell attenuates methamphetamine- and morphine-induced conditioned place preference in rats.

Several lines of evidence have suggested that the glutamatergic system in the nucleus accumbens (NAc) plays an important role in the conditioned rewarding effect of drugs of abuse. In addition, it is recognized that extracellular glutamate is rapidly removed from the synaptic cleft by Na+-dependent glutamate transporters in neurons and glial cells, thereby maintaining physiological levels of glutamate. We previously reported that activation of glutamate uptake by a glutamate transporter activator attenuated the acquisition of conditioned place preference induced by methamphetamine and morphine in mice. In the present study, we examined the effects of gene transfer of a glial glutamate transporter, GLT-1, into the NAc shell by recombinant adenoviruses on methamphetamine- and morphine-induced conditioned place preference in rats. Bilateral infusion of the recombinant adenoviruses into the NAc shell efficiently increased GLT-1 expression surrounding the infusion site, at least during the period 2-8 days after the infusion. In the conditioned place preference paradigm, animals were conditioned with repeated subcutaneous injections of methamphetamine (2 mg/kg) or morphine (3 mg/kg). Intra-NAc shell overexpression of GLT-1 before the conditioning significantly attenuated the conditioned place preference induced by methamphetamine or morphine, when compared with control. However, it had no effect on the somatic signs of naloxone-precipitated morphine withdrawal. These results suggest that GLT-1 within the NAc shell plays an inhibitory role in the conditioned rewarding effects of methamphetamine and morphine but not the physical dependence on morphine.

Adenoviridae↗

PubMed2004

Anatomical substrates for the discriminative stimulus effects of methamphetamine in rats.

Methamphetamine is a psychostimulant drug acting on central monoaminergic neurons to produce both acute psychomotor stimulation and long-lasting behavioral effects including addiction and psychosis. Drug discrimination procedures have been particularly useful in characterizing subjective effects of addictive drugs. In the present study, to identify potential anatomical substrates for the discriminative stimulus effects of methamphetamine, we investigated the drug discrimination-associated Fos expression in Sprague-Dawley rats trained to discriminate methamphetamine from saline under a two-lever fixed ratio 20 (FR-20) schedule of food reinforcement. The rats that fulfilled the criteria for learning the discrimination were anesthetized and perfused 2 h after the drug discrimination test, and Fos immunoreactivity was examined in 15 brain regions. Fos expression in the brains of rats that discriminate methamphetamine from saline was significantly increased in the nucleus accumbens (NAc) and the ventral tegmental area (VTA), but not in other areas including the cerebral cortex, caudate putamen, substantia nigra, hippocampus, amygdala and habenulla, as compared with the expression in control rats that were maintained under the FR-20 schedule. The present findings suggest a role for the VTA and NAc as possible neuronal substrates in the discriminative stimulus effects of methamphetamine.

Animals↗

PubMed1998

Methamphetamine-induced modification of dopamine metabolism in cultured striatal astrocytes.

The role of striatal astrocytes in the metabolic processing (by deamination) of methamphetamine-released dopamine is not known. To investigate the relationship between methamphetamine and dopamine metabolism, we measured 6-hydroxydopamine, dopamine and, 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations following methamphetamine treatment of cultured striatal astrocytes prepared from 1-2 day-old rats. Addition of low concentrations of dopamine (5 x 10(-5) to 5 x 10(-4) M) to cultured astrocytes increased DOPAC levels in a dose-dependent fashion while higher concentrations (5 x 10(-3) to 10(-2) M) inhibited its metabolism and induced formation of 6-hydroxydopamine. Under the same experimental conditions, 10(-4) M dopamine in combination with methamphetamine (10(-5) to 10(-3) M) inhibited DOPAC formation and increased dopamine levels in a dose-dependent fashion, but the formation of intracellular 6-hydroxydopamine was not evident. Deprenyl (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase B, and pargyline (10(-5) or 10(-4) M), a non-selective monoamine oxidase inhibitor, completely inhibited DOPAC formation and increased dopamine levels, while clorgyline (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase-A, only partially inhibited DOPAC formation (42 or 45% of control, respectively). These results support the hypothesis that methamphetamine inhibits monoamine oxidase and causes increases in dopamine levels in cultured striatal astrocytes.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Hydroxyl radical formation following methamphetamine administration to rats.

Administration of neurotoxic doses of methamphetamine (8 mg/kg, intraperitoneally x 4 times, at 2 hr intervals) caused a significant decrease in dopamine and 3,4-dihydroxyphenylacetic acid and an increase in 3-methoxytyramine levels in the striatum along with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in the striatum and hippocampus. In addition, the methamphetamine treatment caused an increase in rat rectal temperature. Intraventricular injection of salicylate 105 min. after the last injection of methamphetamine produced an increase in 2,3- and 2,5-dihydroxybenzoic acid in the striatum and hippocampus. Moreover, the ratio of 2,3-dihydroxybenzoic acid to salicylate was significantly increased in the striatum, but not in the hippocampus. These results indicate that the hydroxyl radical may play an important role in methamphetamine-induced neurotoxicity in rat striatum and that its formation may be the result of methamphetamine-induced release of dopamine.

Animals↗

PubMed1985

The effect of phenothiazine and dibenzazepine pretreatment on the metabolism of methamphetamine in rats.

There was marked variation between p-hydroxylation and N-demethylation of methamphetamine in rats. Within 24 h, 10.4, 24-7 and 4.1% of the administered methamphetamine was excreted in urine unchanged, p-hydroxymethamphetamine (p-OH-MP, free plus conjugated) and also as amphetamine, respectively. Treatment by imipramine, desipramine, chlorpromazine, perphenazine and propericiazine 8 h before the administration with methamphetamine completely inhibited the urinary excretion of p-OH-MP whereas the excretion of amphetamine was enhanced by about 700 to 800%. This effect was also observed in rats treated with imipramine 16 and 24 h before methamphetamine. Phenothiazine and dibenzazepine derivatives reverse the degree of p-hydroxylation and N-demethylation of methamphetamine in-vivo in rats.

Amphetamine↗

PubMed1991

Comparison of sensitization to ambulation-increasing effects of cocaine and methamphetamine after repeated administration in mice.

The effects of repeated (5 times) subcutaneous administration of cocaine (10, 20 or 40 mg kg-1) and methamphetamine (1, 2 or 4 mg kg-1) at 3-4 day intervals have been compared in mice placed individually into tilting activity cages. A progressive enhancement of the ambulation-increasing effect was noted for 3-4 h after each administration, indicating that sensitization occurred. This occurrence and the existence of an optimal dose producing sensitization were similar for both drugs. However, enhancement of the effect after cocaine progressed rapidly and maximum sensitization was observed earlier than after methamphetamine administration. Moreover, the higher doses of cocaine (40 mg kg-1) caused stereotypies concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, methamphetamine caused a more progressive enhancement, but stereotypies with no preconvulsive signs were produced by the higher dose (4 mg kg-1). The respectively, effective doses for the development of enhancement suggested that cocaine was less potent than methamphetamine in producing sensitization. Cross-sensitization occurred between both drugs. Thus, sensitization to cocaine was distinct from that to methamphetamine due to differences in its rapidity, intensity, and the presence or absence of preconvulsive changes.

Animals↗

PubMed1993

Dopamine antagonists can inhibit methamphetamine sensitization, but not cocaine sensitization, when assessed by ambulatory activity in mice.

The repeated subcutaneous administration of methamphetamine (2 mg kg-1) and cocaine (10 mg kg-1) at 3-4 day intervals induced sensitization to their ambulation-increasing effects in mice. Subcutaneous administration of SCH 23390 (R-(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.003-0.03 mg kg-1) and YM-09151-2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide; 0.003-0.03 mg kg-1), the selective dopamine D1 and D2 antagonists, respectively, reduced dose-dependently the acute ambulation-increasing effect of methamphetamine. The development of methamphetamine sensitization was inhibited when it was administered in combination with either SCH 23390 or YM-09151-2 in the repeated administration schedule. Although SCH 23390 (0.01-0.1 mg kg-1) and YM-09151-2 (0.01-0.1 mg kg-1) also reduced the ambulation-increasing effect of cocaine (10 mg kg-1), neither drug inhibited the cocaine sensitization. Mice given cocaine with SCH 23390 (0.03 mg kg-1) or YM-09151-2 (0.03 and 0.1 mg kg-1) showed higher sensitivity than those given cocaine alone. The present results suggest that, although both the dopamine D1 and D2 antagonists reduce the acute stimulant effects of both methamphetamine and cocaine, they are only effective for inhibition of the methamphetamine sensitization. Mechanisms other than the dopaminergic system appear to be involved in the cocaine sensitization.

Animals↗

PubMed2006

Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive and insertive anal sex, respectively, in a sample of men who have sex with men.

OBJECTIVES: There is evidence that methamphetamine and sildenafil (Viagra) use are associated with sexual risk behaviour among men who have sex with men (MSM). We investigated the association of methamphetamine, sildenafil, and other substance use with unprotected receptive and insertive anal sex among MSM by conducting an encounter specific analysis. METHODS: Data were from a cross sectional, community based survey of MSM in San Francisco regarding behaviour during their most recent anal sex encounter. Mulitvariate regression analysed independent associations of specific substance use and demographic variables with unprotected anal sex behaviours. RESULTS: The sample (n = 388) was diverse in race/ethnicity, age, income, education, HIV status, and homosexual/bisexual identification. More than half (53%) reported unprotected anal sex, including insertive (29%) and receptive (37%) during their most recent anal sex encounter; 12% reported unprotected insertive and 17% reported unprotected receptive anal sex with an HIV discordant or unknown partner. Methamphetamine was used by 15% and sildenafil was used by 6% of the men before or during the encounter; 2% used both drugs. In multivariate analysis controlling for demographic factors and other substance use, methamphetamine use was associated with unprotected receptive (odds ratio (OR), 2.03; 95% confidence interval (CI), 1.09 to 3.76) and sildenafil use was associated with unprotected insertive (OR, 6.51; CI, 2.46 to 17.24) anal sex. Effects were stronger with HIV discordant or unknown sex partners specifically. CONCLUSION: Encounter specific associations of methamphetamine and sildenafil use with unprotected receptive and insertive anal sex, respectively, indicate the importance of assessment specificity and tailoring risk reduction efforts to address certain drugs and sexual behavioural roles among MSM.

Adolescent↗

PubMed2001

Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex.

OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.

Adult↗

PubMed2001

Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.

OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.

Adult↗

PubMed2003

Decreased striatal dopamine D1 receptor-stimulated adenylyl cyclase activity in human methamphetamine users.

OBJECTIVE: It has been assumed that some behavioral changes associated with repeated exposure to dopaminergic psychostimulant drugs might be explained by changes in activity of dopamine receptors, including the dopamine D(1) receptor, which is linked by a stimulatory G protein to the effector enzyme adenylyl cyclase. To establish whether dopamine D(1) receptor function might be altered in human methamphetamine users, the authors measured dopamine-stimulated adenylyl cyclase activity in the brain of chronic human users of the drug. METHOD: Adenylyl cyclase activity stimulated by dopamine and by guanylyl-imidodiphosphate (to assess G protein and adenylyl cyclase coupling) was determined in the postmortem brain tissue of 16 methamphetamine users who had used the drug both recently and chronically (i.e., at least 1 year) as well as 21 matched comparison subjects. RESULTS: A 25%-30% decrease in the maximal extent of dopamine stimulation of adenylyl cyclase activity was seen in the striatum (nucleus accumbens, caudate, and putamen) of the methamphetamine users. No changes were found in basal or guanylyl-imidodiphosphate-stimulated enzyme activity. CONCLUSIONS: These data suggest that dopamine receptor function linked to adenylyl cyclase is partially desensitized in the striatum of human methamphetamine users. Decreased dopamine D(1) receptor function might underlie part of the known (drug withdrawal syndrome) or expected (drug tolerance) consequences of methamphetamine exposure in humans.

Adenylyl Cyclases↗

PubMed2000

Psychiatric comorbidity of methamphetamine dependence in a forensic sample.

The objective of this study was to examine the association between psychiatric symptoms and methamphetamine dependence. A four-hour survey was administered to 1,580 arrestees sampled from the 14 most populous counties in California. The survey included items assessing demographic profile, history of substance dependence, and psychiatric symptomatology. In the 12 months prior to the assessment, methamphetamine-dependent individuals were more likely to report depressive symptoms and suicidal ideation than individuals denying methamphetamine dependence, even after controlling for demographic profile and dependence on other drugs. Methamphetamine-dependent individuals also were more likely to report a need for psychiatric assistance at the time of the interview. These findings suggest that methamphetamine-dependent individuals are at greater risk to experience particular psychiatric symptoms. Further study to determine the etiology of these symptoms is warranted.

Adolescent↗

PubMed1996

Methamphetamine effects on cognitive processing during extended wakefulness.

We examined the effects of both 5- and 10-mg/7O kg body weight of d-methamphetamine HCl on high event rate vigilance and tracking performance in a 13.5-hr sustained-performance session during one night of sleep loss. At 0116 hours participants were administered either a 5 mg/70 kg oral dose of d-methamphetamine (n=10), 10 mg/70 kg d-methamphetamine (n=10), or a placebo (n=10) using standard double-blind procedures. Performance on all measures degraded markedly during the night in the placebo group. Both the 5- and 10-mg methamphetamines treatment reversed an initial decline in d', and reversed increases in nonresponses (lapses) and tracking error within approximately 3 hr of administration. No evidence that amphetamine treatment increased impulsive responding (fast guesses) was observed. The magnitude of the performance effects of the methamphetamine treatments was similar at 3 hr postadministration. However, the effects of the 5-mg dose were shorter-lived, disappearing by the last testing session (6.5 hr postadministration), whereas effects of the 10-mg dose tended to remain throughout testing. Both amphetamine treatments decreased subjective sleepiness during the night and tended to increase subjective sleep latencies during a post-testing sleep period.

Adult↗

PubMed1987

Effects of methamphetamine on the twitch response in the rat isolated vas deferens.

The effect of methamphetamine, an indirectly acting sympathomimetic amine, on presynaptic adrenergic regulation in isolated rat vas deferens was studied by comparing it with those of tyramine, cocaine and clonidine. These drugs markedly attenuated the twitch response to electrical field stimulation in a concentration-dependent manner. The relative order of potency for the drugs was: clonidine (10(-10)-3 x 10(-8) M) greater than methamphetamine (10(-8)-3 x 10(-6) M) greater than tyramine (10(-7)-10(-4) M) greater than cocaine (10(-6)-3 x 10(-5) M). Only tyramine (3 x 10(-6)-10(-4) M) elicited a concentration-dependent contractile response, which was abolished by prazosin (10(-6) M) and the reserpinization. The twitch inhibitory effect of these drugs was antagonized by yohimbine (10(-8)-10(-6) M). Both the methamphetamine- and tyramine-induced twitch inhibition were partially (about 50%) attenuated by chronic reserpinization (3 mg/kg, s.c., twice) in combination with alpha-methyl-p-tyrosine (200 mg/kg, s.c., twice), while the clonidine-induced inhibition was not affected by this application at all, and the cocaine-induced twitch inhibition was abolished by the reserpinization. Both the clonidine- and tyramine-induced twitch inhibition were not affected by pretreatment with cocaine (10(-5) M) in combination with estradiol (4 x 10(-5) M), whereas the effect of methamphetamine was slightly attenuated. These results suggest that methamphetamine as well as tyramine and cocaine indirectly activates presynaptic alpha-2 adrenoceptors via norepinephrine released from adrenergic nerves to inhibit the twitch response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1987

Characteristics of effects of repeated scopolamine administration on ambulatory activity in mice and methamphetamine sensitivity in the scopolamine-experienced mice: comparison among 6 strains.

Effects of scopolamine (0.5 mg/kg, s.c.) on ambulatory activity were investigated in 6 strains of mice (dd, ICR, BALB, C57BL, C3H and DBA). Scopolamine increased ambulatory activity, and the sensitivities were in the order of ICR greater than C3H greater than BALB greater than DBA greater than C57BL greater than dd. This was different from that produced by methamphetamine (2 mg/kg, s.c.) where the order was ICR greater than dd greater than DBA greater than C3H greater than C57BL greater than BALB. A tolerance to the ambulation-increasing effect of scopolamine was progressively produced in dd, ICR, C57BL and DBA strains, but not in BALB and C3H strains, when the drug was administered 5 times at intervals of 3-4 days. The repeated scopolamine treatment elicited a major enhancement of the sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) in BALB and C3H strains and a minor enhancement in the C57BL strain, whereas dd, ICR and DBA strains did not exhibit a marked change in the sensitivity to methamphetamine even after the same treatment with scopolamine. These results suggest that the ambulation-increasing effect of scopolamine is different from that of methamphetamine and that the interaction between scopolamine and methamphetamine varies among different strains of mice.

Animals↗