Susceptibility to methamphetamine dependence associated with ...

African Journals Online (AJOL)

Khyber Saify

2015-09-26

Sep 26, 2015 ... 635 healthy controls (525 males and 110 females) were included in the present case–control study. Genotypic ... view based on Diagnostic and Statistical Manual of Mental. Disorders .... was associated with the risk of methamphetamine abused at ... promoter alleles in female patients with panic disorder.

Regional Brain Activity in Abstinent Methamphetamine Dependent Males Following Cue Exposure.

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Malcolm, Robert; Myrick, Hugh; Li, Xingbao; Henderson, Scott; Brady, Kathleen T; George, Mark S; See, Ronald E

Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5). Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (pcues, have increased brain activity in ventral striatum, caudate nucleus and medial frontal cortex which subserve craving, drug-seeking, and drug use.

A Cognitive Behavioral Therapy-Based Text Messaging Intervention for Methamphetamine Dependence

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Keoleian, Victoria; Stalcup, S. Alex; Polcin, Douglas L.; Brown, Michelle; Galloway, Gantt

2013-01-01

Psychosocial treatments for methamphetamine dependence are of limited effectiveness. Thus, a significant need exists for add-on therapy for this substance user disorder. The aim of this study was to develop and test a novel text messaging intervention for use as an adjunct to cognitive behavioral group therapy for methamphetamine users. Text messaging has the potential to support patients in real-time, around the clock. We convened 2 meetings of an expert panel, held 3 focus groups in current and former users, and conducted 15 semi-structured interviews with in-treatment users in order to develop a fully-automated, cognitive behavioral therapy-based text messaging intervention. We then conducted a randomized, crossover pre-test in 5 users seeking treatment. Participants’ ratings of ease of use and functionality of the system were high. During the pre-test we performed real-time assessments via text messaging on daily methamphetamine use, craving levels, and the perceived usefulness of messages; 79% of scheduled assessments were collected. The odds of messages being rated as “very” or “extremely” useful were 6.6 times [95% CI: 2.2, 19.4] higher in the active vs. placebo periods. The intervention is now ready for testing in randomized clinical trials. PMID:24592670

Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons.

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Sobieraj, Jeffery C; Kim, Airee; Fannon, McKenzie J; Mandyam, Chitra D

2016-01-01

Exercise (physical activity) has been proposed as a treatment for drug addiction. In rodents, voluntary wheel running reduces cocaine and nicotine seeking during extinction, and reinstatement of cocaine seeking triggered by drug-cues. The purpose of this study was to examine the effects of chronic wheel running during withdrawal and protracted abstinence on extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats, and to determine a potential neurobiological correlate underlying the effects. Rats were given extended access to methamphetamine (0.05 mg/kg, 6 h/day) for 22 sessions. Rats were withdrawn and were given access to running wheels (wheel runners) or no wheels (sedentary) for 3 weeks after which they experienced extinction and reinstatement of methamphetamine seeking. Extended access to methamphetamine self-administration produced escalation in methamphetamine intake. Methamphetamine experience reduced running output, and conversely, access to wheel running during withdrawal reduced responding during extinction and, context- and cue-induced reinstatement of methamphetamine seeking. Immunohistochemical analysis of brain tissue demonstrated that wheel running during withdrawal did not regulate markers of methamphetamine neurotoxicity (neurogenesis, neuronal nitric oxide synthase, vesicular monoamine transporter-2) and cellular activation (c-Fos) in brain regions involved in relapse to drug seeking. However, reduced methamphetamine seeking was associated with running-induced reduction (and normalization) of the number of tyrosine hydroxylase immunoreactive neurons in the periaqueductal gray (PAG). The present study provides evidence that dopamine neurons of the PAG region show adaptive biochemical changes during methamphetamine seeking in methamphetamine dependent rats and wheel running abolishes these effects. Given that the PAG dopamine neurons project onto the structures of the extended amygdala, the present findings also

A public health response to the methamphetamine epidemic: the implementation of contingency management to treat methamphetamine dependence

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Hare C Bradley

2006-08-01

Full Text Available Abstract Background In response to increases in methamphatemine-associated sexually transmitted diseases, the San Francisco Department of Public Health implemented a contingency management (CM field program called the Positive Reinforcement Opportunity Project (PROP. Methods Methamphetamine-using men who have sex with men (MSM in San Francisco qualified for PROP following expressed interest in the program, provision of an observed urine sample that tested positive for methamphetamine metabolites and self-report of recent methamphetamine use. For 12 weeks, PROP participants provided observed urine samples on Mondays, Wednesdays and Fridays and received vouchers of increasing value for each consecutive sample that tested negative to metabolites of methamphetamine. Vouchers were exchanged for goods and services that promoted a healthy lifestyle. No cash was provided. Primary outcomes included acceptability (number of enrollments/time, impact (clinical response to treatment and cost-effectiveness as cost per patient treated. Results Enrollment in PROP was brisk indicating its acceptability. During the first 10 months of operation, 143 men sought treatment and of these 77.6% were HIV-infected. Of those screened, 111 began CM treatment and averaged 15 (42% methamphetamine-free urine samples out of a possible 36 samples during the 12-week treatment period; 60% completed 4 weeks of treatment; 48% 8 weeks and 30% 12 weeks. Across all participants, an average of $159 (SD = $165 in vouchers or 35.1% of the maximum possible ($453 was provided for these participants. The average cost per participant of the 143 treated was $800. Conclusion Clinical responses to CM in PROP were similar to CM delivered in drug treatment programs, supporting the adaptability and effectiveness of CM to non-traditional drug treatment settings. Costs were reasonable and less than or comparable to other methamphetamine outpatient treatment programs. Further expansion of programs

The levels of triglyceride and total cholesterol in methamphetamine dependence.

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Zhang, Meijuan; Lv, Dezhao; Zhou, Wu; Ji, Lili; Zhou, Beibei; Chen, Han; Gu, Yingying; Zhao, Jiyun; He, Jincai

2017-04-01

The serum triglyceride (TG) and total cholesterol (TC) levels have been reported altered in the traditional drug-dependence (such as marijuana and heroin). However, studies assessing the relationships among serum TC, TG, and methamphetamine (MA)-dependence have not been described well. In this study, our aim is to explore the serum TG and TC levels in large sample of MA-dependent patients. A retrospective study was conducted in 938 MA-dependent patients who were recruited between February 2, 2008 and March 11, 2013, with social characteristics and drug-dependence history (duration of MA use, routes of drug administration, and daily dose were collected). Then, the serum levels of TC, TG, glucose (GLU), body mass index (BMI), and blood pressure were measured among the participants. Meanwhile, 985 age- and gender-matched healthy people in the physical examination center were selected as control group. Compared with the control group, significant decreases of TC, TG, GLU, and BMI were observed in MA-dependent patients (P < 0.05). Besides, we found that the daily dose of MA use was associated with TC (β = -0.079, P = 0.015) and the duration of MA use was independently related to BMI (β = -0.071, P = 0.031). This study demonstrated that the levels of TC, TG, GLU, and BMI factors altered in the MA-dependent patients. In addition, there is a negative association between MA dependence and TC and BMI.

Feasibility of Ecological Momentary Assessment Using Cellular Telephones in Methamphetamine Dependent Subjects

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John Mendelson

2008-01-01

Full Text Available Background: Predictors of relapse to methamphetamine use are poorly understood. State variables may play an important role in relapse, but they have been difficult to measure at frequent intervals in outpatients.Methods: We conducted a feasibility study of the use of cellular telephones to collect state variable data from outpatients. Six subjects in treatment for methamphetamine dependence were called three times per weekday for approximately seven weeks. Seven questionnaires were administered that assessed craving, stress, affect and current type of location and social environment.Results: 395/606 (65% of calls attempted were completed. The mean time to complete each call was 4.9 (s.d. 1.8 minutes and the mean time to complete each item was 8.4 (s.d. 4.8 seconds. Subjects rated the acceptability of the procedures as good. All six cellular phones and battery chargers were returned undamaged.Conclusion: Cellular telephones are a feasible method for collecting state data from methamphetamine dependent outpatients.

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

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Ruha, Anne-Michelle; Yarema, Mark C

2006-12-01

To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Study of Serum Malondialdehyde Level in Opioid and Methamphetamine Dependent Patients

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Khadije Najafi

2017-12-01

Full Text Available Opioid compound and methamphetamine are commonly used in drug abuse; these can disrupt the normal function of cellular and molecular systems, leading to several events such as oxidative stress, aging, apoptosis, and necrosis. Malondialdehyde (MDA is the most important biomarker for evaluation of oxidative stress and determination of lipid peroxidation. In this study, 42 drug abusers and 22 healthy persons participated as case and control groups, respectively. MDA in volunteer sera was determined by high-performance liquid chromatography (HPLC with fluorescence detection after pre-column derivatization using thiobarbituric acid. The analysis was performed on a ODS column by spectrofluorometer detection, operated at excitation of 515 nm and emission of 535 nm. A mixture of phosphate buffer (0.05 M, pH 6.8, containing potassium monobasic phosphate and methanol (60:40, v/v at a flow rate of 1 ml/min, was used as the mobile phase. The retention time of MDA-TBA was 3.2 min. Our findings showed that the MDA level increased in the opioid and methamphetamine abusers when compared to the control group (P<0.05; however, no significant difference was observed between the opioid and methamphetamine groups. A state of oxidative stress during biological processes leads to lipid peroxidation, DNA damage, biomolecule dysfunctions, and many other diseases. Since it is impossible to eradicate the drug addiction, we should reduce the side effects of drug abuse, such as oxidative stress, by intake of proper nutrition and antioxidants.

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

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Boyd R Rorabaugh

Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

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Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

2017-01-01

Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder

OpenAIRE

Heinzerling, Keith G.; Demirdjian, Levon; Wu, Yingnian; Shoptaw, Steven

2015-01-01

Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correcti...

Sex- and histamine-dependent long-term cognitive effects of methamphetamine exposure

NARCIS (Netherlands)

Acevedo, S.F.; de Esch, I.J.P.; Raber, J.

2007-01-01

As prenatal methamphetamine (MA) exposure results in long-term hippocampus-dependent cognitive deficits, the increased MA use in women of childbearing age is of great concern. As mice are most commonly used in genetic models, we started to study the potential effects of neonatal MA exposure in

Effects of methamphetamine dependence and HIV infection on cerebral morphology

DEFF Research Database (Denmark)

Jernigan, Terry Lynne; Gamst, Abthony C; Archibald, Sarah L.

2005-01-01

increases, and in one of these structures-the nucleus accumbens-there appeared to be a larger effect in younger methamphetamine abusers. Neurocognitive impairment was associated with decreased cortical volumes in HIV-positive participants but with increased cortical volumes in methamphetamine...... the results of the present study provide little information about the specific mechanisms leading to the unexpected methamphetamine effects, they may be related to glial activation or neuritic growth, both of which have been associated with methamphetamine exposure in animal studies. These results have...

Social cognition and aggression in methamphetamine dependence with and without a history of psychosis.

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Uhlmann, Anne; Ipser, Jonathan C; Wilson, Don; Stein, Dan J

2018-04-01

In substance use and psychotic disorders, socially problematic behaviours, such as high aggression may, in part, be explained by deficits in social cognition skills, like the detection of emotions or intentions in others. The aim of this study was to assess the magnitude of social cognition impairment and its association with aggression in individuals with methamphetamine (MA) dependence, methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21 CTRL participants performed a facial morphing emotion recognition task (ERT) across four basic emotions (anger, fear, happiness and sadness) and the reading the mind in the eyes task (RMET), and completed the aggression questionnaire. Both MA-dependent groups showed impairment in social cognition in terms of lower RMET scores relative to CTRL participants (MA; p = .047; MAP: p MAP (p = .040), compared to MA-dependent participants. While deficits in recognising emotional expressions were restricted to anger in the MA group (p = .020), a generalized impairment across all four emotions was observed in MAP (all p ≤ .001). Additionally, both patient groups demonstrated higher levels of aggression than CTRLs, yet no association was found with social cognition. This study supported the notion of deficits in recognising facial emotional expressions and inferring mental states of others in MA dependence, with additional impairments in MAP. Failure to detect an association between social cognitive impairment and aggressive behaviour may implicate independent disturbances of the two phenomena in MA dependence.

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

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Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

2017-09-01

Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder.

Science.gov (United States)

Heinzerling, Keith G; Demirdjian, Levon; Wu, Yingnian; Shoptaw, Steven

2016-03-01

Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Single nucleotide polymorphism near CREB1, rs7591784, is associated with pretreatment methamphetamine use frequency and outcome of outpatient treatment for methamphetamine use disorder

Science.gov (United States)

Heinzerling, Keith G.; Demirdjian, Levon; Wu, Yingnian; Shoptaw, Steven

2016-01-01

Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders. PMID:26736037

Oral health of the methamphetamine abuser.

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Donaldson, Mark; Goodchild, Jason H

2006-11-01

The pharmacology of methamphetamine is reviewed, and the effects of methamphetamine use on oral health are described. Methamphetamine is a highly addictive amphetamine analogue, initially synthesized in 1919. Illicit methamphetamine use leads to devastating effects on health, particularly the dentition. Illegal production of methamphetamine has skyrocketed in recent years, as have the number of users. The chief complaint of methamphetamine users is xerostomia. Without the protective effects of saliva, caries development in these patients is rampant. The typical pattern of decay involves the facial and cervical areas of both the maxillary and mandibular teeth, with eventual progression to frank coronal involvement. The acidic substances used to manufacture this drug have also been implicated as a cause of tooth decay and wear in users, as has bruxism as a result of drug-induced hyperactivity. When possible, these patients should be referred to a dentist to improve their oral health status and minimize the potential for adverse cardiovascular sequelae. Other preventive measures for methamphetamine users include stimulating saliva flow and increasing fluoride supplementation. Pharmacists should also counsel users to avoid carbohydrate-rich soft drinks in favor of water. Oral moisturizers may also be effective. Methamphetamine use causes xerostomia secondary to sympathetic central nervous system activation, rampant caries caused by high-sugar intake in the absence of protective saliva, and bruxism as a result of hyperactivity. Practitioners should know how to recognize the signs of and manage the oral health of patients with a history of methamphetamine use.

Functional and Structural Brain Changes Associated with Methamphetamine Abuse

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Bruce R. Russell

2012-10-01

Full Text Available Methamphetamine (MA is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET and functional and structural magnetic resonance imaging (MRI. The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

Personality traits and mental health states of methamphetamine-dependent and methamphetamine non-using MSM.

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Solomon, Todd M; Kiang, Mathew V; Halkitis, Perry N; Moeller, Robert W; Pappas, Molly K

2010-02-01

This analysis considers the relation between personality traits, mental health states and methamphetamine (MA) use in 60 men who have sex with men (MSM). Thirty MA-dependent and 30 MA non-using MSM were assessed on the Neo Five Factor Inventory, the Brief Symptom Inventory, the Perceived Stress Scale, and the Posttraumatic Stress Disorder Checklist-Civilian Version tests. Our results indicate differences between groups on a variety of measures of personality traits and mental states. Specifically, MA-dependent participants were found to be more Neurotic, less Open, less Agreeable, and less Conscientious. Further, MA-dependent participants were found to have higher levels of Paranoid Ideation and higher levels of Interpersonal Sensitivity. Given the high prevalence of MA use in the MSM community and the association between MA use and sexual risk taking, our findings provided a clearer understanding of how individual personality traits may be a factor in the continued use of this drug among MSM. Further research should seek to incorporate individual personality traits into the development of efficacious MA-specific treatment interventions.

Plasma inflammatory factors are associated with anxiety, depression, and cognitive problems in adults with and without methamphetamine dependence: An exploratory protein array study

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Marilyn eHuckans

2015-12-01

Full Text Available Objectives: It is hypothesized that immune factors influence addictive behaviors and contribute to relapse. The primary study objectives were to: 1 compare neuropsychiatric symptoms across adults with active methamphetamine dependence, in early remission from methamphetamine dependence, and with no history of substance dependence, 2 determine whether active or recent methamphetamine dependence affects the expression of immune factors, and 3 evaluate the association between immune factor levels and neuropsychiatric symptoms. Methods: A cross-sectional study was conducted using between group comparisons and regression analyses to investigate associations among variables. Eighty-four adults were recruited into control (n = 31, methamphetamine (MA-active (n = 17, or MA-remission (n = 36 groups. Participants completed self-report measures of anxiety, depression, and memory complaints and objective tests of attention and executive function. Blood samples were collected, and a panel of immune factors was measured using multiplex technology. Results: Relative to controls, MA dependent adults evidenced greater anxiety and depression during active use (p < 0.001 and remission (p < 0.007, and more attention, memory, and executive problems during remission (p < 0.01 but not active dependence. Regression analyses identified 10 immune factors (putatively associated with cytokine-cytokine receptor interactions associated with anxiety, depression, and memory problems. Conclusion: While psychiatric symptoms are present during active methamphetamine dependence and remission, at least some cognitive difficulties emerge only during remission. Altered expression of a network of immune factors contributes to neuropsychiatric symptom severity.

Neuroimmune Basis of Methamphetamine Toxicity

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Loftis, Jennifer M.; Janowsky, Aaron

2015-01-01

Although it is not known which antigen-specific immune responses (or if antigen-specific immune responses) are relevant or required for methamphetamine's neurotoxic effects, it is apparent that methamphetamine exposure is associated with significant effects on adaptive and innate immunity. Alterations in lymphocyte activity and number, changes in cytokine signaling, impairments in phagocytic functions, and glial activation and gliosis have all been reported. These drug-induced changes in immune response, particularly within the CNS, are now thought to play a critical role in the addiction process for methamphetamine dependence as well as for other substance use disorders. In Section 2, methamphetamine's effects on glial cell (e.g., microglia and astrocytes) activity and inflammatory signaling cascades are summarized, including how alterations in immune cell function can induce the neurotoxic and addictive effects of methamphetamine. Section 2 also describes neurotransmitter involvement in the modulation of methamphetamine's inflammatory effects. Section 3 discusses the very recent use of pharmacological and genetic animal models which have helped elucidate the behavioral effects of methamphetamine's neurotoxic effects and the role of the immune system. Section 4 is focused on the effects of methamphetamine on blood–brain barrier integrity and associated immune consequences. Clinical considerations such as the combined effects of methamphetamine and HIV and/or HCV on brain structure and function are included in Section 4. Finally, in Section 5, immune-based treatment strategies are reviewed, with a focus on vaccine development, neuroimmune therapies, and other anti-inflammatory approaches. PMID:25175865

Exercise for methamphetamine dependence: rationale, design, and methodology.

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Mooney, Larissa J; Cooper, Christopher; London, Edythe D; Chudzynski, Joy; Dolezal, Brett; Dickerson, Daniel; Brecht, Mary-Lynn; Peñate, Jose; Rawson, Richard A

2014-01-01

Effective pharmacotherapies to treat methamphetamine (MA) dependence have not been identified, and behavioral therapies are marginally effective. Based on behavioral studies demonstrating the potential efficacy of aerobic exercise for improving depressive symptoms, anxiety, cognitive deficits, and substance use outcomes, the study described here is examining exercise as a potential treatment for MA-dependent individuals. This study is randomizing 150 participants with MA dependence at a residential treatment facility for addictive disorders to receive either a thrice-weekly structured aerobic and resistance exercise intervention or a health education condition. Recruitment commenced in March, 2010. Enrollment and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Seeking evidence for a possibly effective adjunct to traditional behavioral approaches for treatment of MA dependence, this study is assessing the ability of an 8-week aerobic and resistance exercise protocol to reduce relapse to MA use during a 12-week follow-up period after discharge from residential-based treatment. The study also is evaluating improvements in health and functional outcomes during and after the protocol. This paper describes the design and methods of the study. Copyright © 2013 Elsevier Inc. All rights reserved.

Higher defibrillation threshold in methamphetamine cardiomyopathy patients with implantable cardioverter-defibrillator

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Rakesh Malhotra

2017-11-01

Full Text Available Introduction: Identification of patients with an increased risk of high defibrillation thresholds (DFTs is important in planning implantable cardioverter-defibrillator (ICD procedures. Clinical observations have suggested that patients with methamphetamine cardiomyopathy (MACMP have significantly elevated defibrillation thresholds. We hypothesized that MACMP patients would have higher DFT thresholds than controls and would require procedural changes during ICD implantation to accommodate higher thresholds. Methods: We identified consecutive patients with MACMP undergoing ICD implantation at the academic center from 2003 to 2007. We then compared DFTs against age-and sex-matched controls. Results: The MACMP (n = 10 group showed significantly increased DFT thresholds (23.7 ± 6.7 J compared with age and sex-matched controls (14.5 ± 4.6 J, p < 0.005. Additionally, patients with MACMP had evidence of more severe congestive heart failure, with increased B-type natrieutic protein (BNP levels (1173 ± 784 vs 260 ± 349, p = 0.02 and decreased left ventricular ejection fraction (LVEF (17.8 ± 9.4 vs 35.9 ± 15.2, p = 0.02. MACMP patients required high output devices than controls (50% versus 0%, p = 0.03. Differences between groups remained significant despite adjusting for LVEF. Conclusions: Planning for ICD implantation should take into consideration a history of methamphetamine abuse, mandating DFT testing and empiric consideration of high output devices for such patients. Keywords: Methamphetamine cardiomyopathy, Implantable cardioverter-defibrillatior, Defibrillation threshold testing, B-type natriuretic peptide, Ejection fraction

Methamphetamine psychosis: epidemiology and management.

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Glasner-Edwards, Suzette; Mooney, Larissa J

2014-12-01

Psychotic symptoms and syndromes are frequently experienced among individuals who use methamphetamine, with recent estimates of up to approximately 40 % of users affected. Although transient in a large proportion of users, acute symptoms can include agitation, violence, and delusions, and may require management in an inpatient psychiatric or other crisis intervention setting. In a subset of individuals, psychosis can recur and persist and may be difficult to distinguish from a primary psychotic disorder such as schizophrenia. Differential diagnosis of primary vs. substance-induced psychotic disorders among methamphetamine users is challenging; nevertheless, with careful assessment of the temporal relationship of symptoms to methamphetamine use, aided by state-of-the art psychodiagnostic assessment instruments and use of objective indicators of recent substance use (i.e., urine toxicology assays), coupled with collateral clinical data gathered from the family or others close to the individual, diagnostic accuracy can be optimized and the individual can be appropriately matched to a plan of treatment. The pharmacological treatment of acute methamphetamine-induced psychosis may include the use of antipsychotic medications as well as benzodiazepines, although symptoms may resolve without pharmacological treatment if the user is able to achieve a period of abstinence from methamphetamine. Importantly, psychosocial treatment for methamphetamine dependence has a strong evidence base and is the optimal first-line treatment approach to reducing rates of psychosis among individuals who use methamphetamines. Prevention of methamphetamine relapse is the most direct means of preventing recurrence of psychotic symptoms and syndromes. Long-term management of individuals presenting with recurrent and persistent psychosis, even in the absence of methamphetamine use, may include both behavioral treatment to prevent resumption of methamphetamine use and pharmacological treatment

Methamphetamine Use and Oral Health

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FOR THE DENTAL PATIENT ... Methamphetamine use and oral health M ethamphetamine is an inexpensive, easy-to-make illicit drug. It is known by several street ... and in ever-larger doses. The use of methamphetamine is on the rise in the United States, ...

Methamphetamine (Meth)

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... Enter Search Term(s): Teens / Drug Facts / Methamphetamine (Meth) Methamphetamine (Meth) Street names: Crank, Crystal, Speed Print Expand All Revised March 2017 What is methamphetamine (meth)? Photo by DEA Crystal Methamphetamine Also known ...

The effect of N-acetylcysteine or bupropion on methamphetamine self-administration and methamphetamine-triggered reinstatement of female rats.

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Charntikov, Sergios; Pittenger, Steven T; Pudiak, Cindy M; Bevins, Rick A

2018-03-28

N-acetylcysteine and bupropion are two promising candidate medications for treatment of substance use disorder. The effects of N-acetylcysteine or bupropion on methamphetamine self-administration of female rats are not well understood. To fill this gap, this study assessed the effects of N-acetylcysteine (0, 30, 60, or 120 mg/kg) and bupropion (0, 10, 30, and 60 mg/kg) on methamphetamine self-administration of female rats across the natural estrous cycle. Following a completed dose-response curve, responding for methamphetamine self-administration was extinguished and the effects of N-acetylcysteine or bupropion on methamphetamine-triggered reinstatement was evaluated in separate experiments. N-acetylcysteine did not decrease responding maintained by methamphetamine or methamphetamine-triggered reinstatement. Bupropion significantly decreased methamphetamine self-administration and methamphetamine-triggered reinstatement in female rats with highest dose (60 mg/kg) also significantly decreasing general chamber activity. In a companion experiment, testing the effect of bupropion on responding maintained by sucrose, we confirmed non-specificity of bupropion's effects as bupropion also decreased responding for sucrose. Considered together, our findings suggest that while N-acetylcysteine has considerable promise for treatment of cocaine dependence it may not generalize to other stimulants like methamphetamine. Furthermore, although bupropion has been shown to effectively decrease methamphetamine self-administration, and presently methamphetamine-triggered reinstatement, its locomotor and reward suppressing effects warrant further investigation including both sexes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Methamphetamine Related Radiculopathy: Case Series and Review of Literature

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Mohsen Foroughipour

2013-06-01

Full Text Available Background: Peripheral nervous injury and neuromuscular complications from methamphetamine abuse has not been reported. The mechanism is not yet identified. Methods: Eight patients with lower extremity weakness following methamphetamine abuse were reported during December 2009 to May 2010. Results: Patients presented with lower extremity weakness. All patients were co-abusers of methamphetamine and opioids. Other clinical manifestations comprised of distal paresthesia of the lower extremities with progression to proximal portions, with minimal sensory involvement in the distal of the lower extremities. Electrodiagnostic findings were consistent with lumbosacral Radiculopathy. Vital signs were unremarkable and all laboratory tests were within normal limits. Follow-up examination after three months showed improvement of weakness in 3 patients. Conclusion: For patients with a history of illicit drug abuse and acute neuromuscular weakness, methamphetamine or heroin toxicity should be taken into account. Hence, urine morphine and amphetamine/ methamphetamine tests should be performed and serum lead and thallium levels should be evaluated. In addition, rhabdomyolysis and myoglobinuria should be worked up.

Age-dependent methamphetamine-induced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity.

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Truong, Jannine G; Wilkins, Diana G; Baudys, Jakub; Crouch, Dennis J; Johnson-Davis, Kamisha L; Gibb, James W; Hanson, Glen R; Fleckenstein, Annette E

2005-09-01

Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied. In adult rodents, toxic effects of methamphetamine may result partly from aberrant cytosolic dopamine accumulation and subsequent reactive oxygen species formation. The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and perhaps protection against dopamine-associated oxidative consequences. Accordingly, aberrant VMAT-2 function may contribute to the methamphetamine-induced persistent dopaminergic deficits. Hence, this study examined effects of methamphetamine on VMAT-2 in adolescent (postnatal day 40) and young adult (postnatal day 90) rats. Results revealed that high-dose methamphetamine treatment caused greater acute (within 1 h) decreases in vesicular dopamine uptake in postnatal day 90 versus 40 rats, as determined in a nonmembrane-associated subcellular fraction. Greater basal levels of VMAT-2 at postnatal day 90 versus 40 in this purified fraction seemed to contribute to the larger effect. Basal tissue dopamine content was also greater in postnatal day 90 versus 40 rats. In addition, postnatal day 90 rats were more susceptible to methamphetamine-induced persistent dopaminergic deficits as assessed by measuring VMAT-2 activity and dopamine content 7 days after treatment, even if drug doses were adjusted for age-related pharmacokinetic differences. Together, these data demonstrate dynamic changes in VMAT-2 susceptibility to methamphetamine as a function of development. Implications with regard to methamphetamine-induced dopaminergic deficits, as well as dopamine-associated neurodegenerative disorders such as Parkinson's disease, are discussed.

Crystalline methamphetamine use and methamphetamine-related harms in Australia.

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Degenhardt, Louisa; Sara, Grant; McKetin, Rebecca; Roxburgh, Amanda; Dobbins, Timothy; Farrell, Michael; Burns, Lucinda; Hall, Wayne D

2017-03-01

Concerns about crystal methamphetamine use and harm have increased in multiple countries. This paper describes how changes in the availability and use of crystal methamphetamine have impacted on methamphetamine-related harms in Australia. Data on methamphetamine use were obtained from population-level surveys, health service data and surveys of drug use among sentinel groups of ecstasy users and people who inject drugs. Data were obtained on seizures, arrests, clandestine laboratory detections, hospital separations, mental health unit admissions, drug telephone helpline calls and drug treatment episodes. Segmented linear regression models were fitted to identify changes in these series using log-transformed data where appropriate. The availability of crystal methamphetamine has increased as evidenced by increased laboratory detections, domestic seizures and purity of the seized drug. Population surveys do not report an increase in the number of people who used at least once in the past year. However, more users report using crystal methamphetamine rather than lower-purity powder methamphetamine and more regular use. Indicators of methamphetamine-related harms have increased in parallel with this change. Amphetamine-related helpline calls, drug treatment, arrests and hospital admissions for amphetamine disorders and psychosis all peaked in the mid-2000s, declined for several years and have increased steeply since 2010. The increased availability and use of crystal methamphetamine have been associated with increased regular use and harms. Treatment is required for those experiencing problems and the capacity of health services to provide care needs to be enhanced.[Degenhardt L, Sara G, Connor JP, McKetin R, Roxburgh A, Dobbins T, Farrell M, Burns L, Hall WD. Crystalline methamphetamine use and methamphetamine-related harms in Australia. Drug Alcohol Rev 2017;36:160-170]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

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Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

2017-06-01

Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

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Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

2014-01-01

Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Theories of addiction: methamphetamine users' explanations for continuing drug use and relapse.

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Newton, Thomas F; De La Garza, Richard; Kalechstein, Ari D; Tziortzis, Desey; Jacobsen, Caitlin A

2009-01-01

A variety of preclinical models have been constructed to emphasize unique aspects of addiction-like behavior. These include Negative Reinforcement ("Pain Avoidance"), Positive Reinforcement ("Pleasure Seeking"), Incentive Salience ("Craving"), Stimulus Response Learning ("Habits"), and Inhibitory Control Dysfunction ("Impulsivity"). We used a survey to better understand why methamphetamine-dependent research volunteers (N = 73) continue to use methamphetamine, or relapse to methamphetamine use after a period of cessation of use. All participants met DSM-IV criteria for methamphetamine abuse or dependence, and did not meet criteria for other current Axis I psychiatric disorders or dependence on other drugs of abuse, other than nicotine. The questionnaire consisted of a series of face-valid questions regarding drug use, which in this case referred to methamphetamine use. Examples of questions include: "Do you use drugs mostly to make bad feelings like boredom, loneliness, or apathy go away?", "Do you use drugs mostly because you want to get high?", "Do you use drugs mostly because of cravings?", "Do you find yourself getting ready to take drugs without thinking about it?", and "Do you impulsively take drugs?". The scale was anchored at 1 (not at all) and 7 (very much). For each question, the numbers of participants rating each question negatively (1 or 2), neither negatively or affirmatively (3-5), and affirmatively (6 or 7) were tabulated. The greatest number of respondents (56%) affirmed that they used drugs due to "pleasure seeking." The next highest categories selected were "impulsivity" (27%) and "habits"(25%). Surprisingly, many participants reported that "pain avoidance" (30%) and "craving" (30%) were not important for their drug use. Results from this study support the contention that methamphetamine users (and probably other drug users as well) are more heterogeneous than is often appreciated, and imply that treatment development might be more successful if

PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and (—)-Cocaine

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Fowler, Joanna S.; Kroll, Carsten; Ferrieri, Richard; Alexoff, David; Logan, Jean; Dewey, Stephen L.; Schiffer, Wynne; Schlyer, David; Carter, Pauline; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Benveniste, Helene; Vaska, Paul; Volkow, Nora D.

2009-01-01

The methamphetamine molecule has a chiral center and exists as 2 enantiomers, d-methamphetamine (the more active enantiomer) and l-methamphetamine (the less active enantiomer). d-Methamphetamine is associated with more intense stimulant effects and higher abuse liability. The objective of this study was to measure the pharmacokinetics of d-methamphetamine for comparison with both l-methamphetamine and (—)-cocaine in the baboon brain and peripheral organs and to assess the saturability and pharmacologic specificity of binding. Methods d- and l-methamphetamine and (—)-cocaine were labeled with 11C via alkylation of the norprecursors with 11C-methyl iodide using literature methods. Six different baboons were studied in 11 PET sessions at which 2 radiotracer injections were administered 2–3 h apart to determine the distribution and kinetics of 11C-d-methamphetamine in brain and peripheral organs. Saturability and pharmacologic specificity were assessed using pretreatment with d-methamphetamine, methylphenidate, and tetrabenazine. 11C-d-Methamphetamine pharmacokinetics were compared with 11C-l-methamphetamine and 11C-(—)-cocaine in both brain and peripheral organs in the same animal. Results 11C-d- and l-methamphetamine both showed high uptake and widespread distribution in the brain. Pharmacokinetics did not differ between enantiomers, and the cerebellum peaked earlier and cleared more quickly than the striatum for both. 11C-d-Methamphetamine distribution volume ratio was not substantially affected by pretreatment with methamphetamine, methylphenidate, or tetrabenazine. Both enantiomers showed rapid, high uptake and clearance in the heart and lungs and slower uptake and clearance in the liver and kidneys. A comparison of 11C-d-methamphetamine and 11C-(—)-cocaine showed that 11C-d-methamphetamine peaked later in the brain than did 11C-(—)-cocaine and cleared more slowly. The 2 drugs showed similar behavior in all peripheral organs examined except the kidneys

The impact of age, HIV serostatus and seroconversion on methamphetamine use.

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Montoya, Jessica L; Cattie, Jordan; Morgan, Erin; Woods, Steven Paul; Cherner, Mariana; Moore, David J; Atkinson, J Hampton; Grant, Igor

2016-03-01

Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. Study aims were to investigate whether (i) methamphetamine use differs by age and HIV serostatus, and (ii) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (β = -0.16, p = 0.01) and a fewer number of days (β = -0.18, p = 0.004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e. grams per day used) was greater among the younger, relative to the older, HIV+ group (p = 0.02), and increased for both age groups following seroconversion (p methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum.

Antisocial personality disorder predicts methamphetamine treatment outcomes in homeless, substance-dependent men who have sex with men.

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Fletcher, Jesse B; Reback, Cathy J

2013-09-01

One-hundred-thirty-one homeless, substance-dependent MSM were enrolled in a randomized controlled trial to assess the efficacy of a contingency management (CM) intervention for reducing substance use and increasing healthy behavior. Participants were randomized into conditions that either provided additional rewards for substance abstinence and/or health-promoting/prosocial behaviors ("CM-full"; n=64) or for study compliance and attendance only ("CM-lite"; n=67). The purpose of this secondary analysis was to determine the affect of ASPD status on two primary study outcomes: methamphetamine abstinence, and engagement in prosocial/health-promoting behavior. Analyses revealed that individuals with ASPD provided more methamphetamine-negative urine samples (37.5%) than participants without ASPD (30.6%). When controlling for participant sociodemographics and condition assignment, the magnitude of this predicted difference increases to 10% and reached statistical significance (p<.05). On average, participants with ASPD earned fewer vouchers for health-promoting/prosocial behaviors than participants without ASPD ($10.21 [SD=$7.02] versus $18.38 [SD=$13.60]; p<.01). Participants with ASPD displayed superior methamphetamine abstinence outcomes regardless of CM schedule; even with potentially unlimited positive reinforcement, individuals with ASPD displayed suboptimal outcomes in achieving health-promoting/prosocial behaviors. Copyright © 2013 Elsevier Inc. All rights reserved.

Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.

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Lin, Yin Chiu; Kuo, Yu-Min; Liao, Pao-Chi; Cherng, Chianfang G; Su, Su-Wen; Yu, Lung

2007-04-30

Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.

Agmatine attenuates the discriminative stimulus and hyperthermic effects of methamphetamine in male rats.

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Thorn, David A; Li, Jiuzhou; Qiu, Yanyan; Li, Jun-Xu

2016-09-01

Methamphetamine abuse remains an alarming public heath challenge, with no approved pharmacotherapies available. Agmatine is a naturally occurring cationic polyamine that has previously been shown to attenuate the rewarding and psychomotor-sensitizing effects of methamphetamine. This study examined the effects of agmatine on the discriminative stimulus and hyperthermic effects of methamphetamine. Adult male rats were trained to discriminate 0.32 mg/kg methamphetamine from saline. Methamphetamine dose dependently increased drug-associated lever responding. The nonselective dopamine receptor antagonist haloperidol (0.1 mg/kg) significantly attenuated the discriminative stimulus effects of methamphetamine (5.9-fold rightward shift). Agmatine (10-100 mg/kg) did not substitute for methamphetamine, but significantly attenuated the stimulus effects of methamphetamine, leading to a maximum of a 3.5-fold rightward shift. Acute 10 mg/kg methamphetamine increased the rectal temperature by a maximum of 1.96±0.17°C. Agmatine (10-32 mg/kg) pretreatment significantly attenuated the hyperthermic effect of methamphetamine. Agmatine (10 mg/kg) also significantly reversed methamphetamine-induced temperature increase. Together, these results support further exploration of the value that agmatine may have for the treatment of methamphetamine abuse and overdose.

The Impact of the Media in Influencing Extension's Perceptions of Methamphetamine

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Beaudreault, Amy R.

2013-01-01

The study reported here explored media dependency and moral panic involving methamphetamine perceptions among a national sample of Extension Directors through survey methodology. With a 70.0% response rate, the questionnaire concentrated on demographics; methamphetamine knowledge, information sources, and dependency; and perceptions of the media.…

Intracellular Methamphetamine Prevents the Dopamine-induced Enhancement of Neuronal Firing*

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Saha, Kaustuv; Sambo, Danielle; Richardson, Ben D.; Lin, Landon M.; Butler, Brittany; Villarroel, Laura; Khoshbouei, Habibeh

2014-01-01

The dysregulation of the dopaminergic system is implicated in multiple neurological and neuropsychiatric disorders such as Parkinson disease and drug addiction. The primary target of psychostimulants such as amphetamine and methamphetamine is the dopamine transporter (DAT), the major regulator of extracellular dopamine levels in the brain. However, the behavioral and neurophysiological correlates of methamphetamine and amphetamine administration are unique from one another, thereby suggesting these two compounds impact dopaminergic neurotransmission differentially. We further examined the unique mechanisms by which amphetamine and methamphetamine regulate DAT function and dopamine neurotransmission; in the present study we examined the impact of extracellular and intracellular amphetamine and methamphetamine on the spontaneous firing of cultured midbrain dopaminergic neurons and isolated DAT-mediated current. In dopaminergic neurons the spontaneous firing rate was enhanced by extracellular application of amphetamine > dopamine > methamphetamine and was DAT-dependent. Amphetamine > methamphetamine similarly enhanced DAT-mediated inward current, which was sensitive to isosmotic substitution of Na+ or Cl− ion. Although isosmotic substitution of extracellular Na+ ions blocked amphetamine and methamphetamine-induced DAT-mediated inward current similarly, the removal of extracellular Cl− ions preferentially blocked amphetamine-induced inward current. The intracellular application of methamphetamine, but not amphetamine, prevented the dopamine-induced increase in the spontaneous firing of dopaminergic neurons and the corresponding DAT-mediated inward current. The results reveal a new mechanism for methamphetamine-induced dysregulation of dopaminergic neurons. PMID:24962577

Impaired Arterial Smooth Muscle Cell Vasodilatory Function In Methamphetamine Users

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Ghaemeh Nabaei

2017-02-01

Full Text Available Objectives: Methamphetamine use is a strong risk factor for stroke. This study was designed to evaluate arterial function and structure in methamphetamine users ultrasonographically. Methods: In a cross-sectional study, 20 methamphetamine users and 21 controls, aged between 20 and 40years, were enrolled. Common carotid artery intima-media thickness (CCA-IMT marker of early atherogenesis, flow-mediated dilatation (FMD determinants of endothelium-dependent vasodilation, and nitroglycerine-mediated dilatation (NMD independent marker of vasodilation were measured in two groups. Results: There were no significant differences between the two groups regarding demographic and metabolic characteristics. The mean (±SD CCA-IMT in methamphetamine users was 0.58±0.09mm, versus 0.59±0.07mm in the controls (p=0.84. Likewise, FMD% was not significantly different between the two groups [7.6±6.1% in methamphetamine users vs. 8.2±5.1% in the controls; p=0.72], nor were peak flow and shear rate after hyperemia. However, NMD% was considerably decreased in the methamphetamine users [8.5±7.8% in methamphetamine users vs. 13.4±6.2% in controls; p=0.03]. Conclusion: According to our results, NMD is reduced among otherwise healthy methamphetamine users, which represents smooth muscle dysfunction in this group. This may contribute to the high risk of stroke among methamphetamine users.

Effects of Circadian Disruption on Methamphetamine Consumption in Methamphetamine-Exposed Rats

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Doyle, Susan E.; Feng, Hanting; Garber, Garrett; Menaker, Michael; Lynch, Wendy J.

2015-01-01

Rationale A substantial number of clinical studies indicate associations between sleep abnormalities and drug abuse; however, the role played by the circadian system in the development of addiction is largely unknown. Objective The aim of this study was to examine the effects of experimentally induced chronic jet lag on methamphetamine consumption in a rat model of methamphetamine drinking. Methods Male Sprague-Dawley rats (n=32) were housed in running wheel cages in a 12:12 light:dark cycle. One group of rats (n=16) was given two weeks of forced methamphetamine consumption (0.01% in drinking water; meth pre-exposed) while a second group (n=16, not pre-exposed) received water only. This was followed by a two week abstinence period during which half of the animals from each group were exposed to 4 consecutive 6-hr advancing phase shifts of the light:dark cycle, while the other half remained on the original light:dark cycle. Methamphetamine consumption was assessed in all rats following the deprivation period using a two-bottle choice paradigm. Results Methamphetamine consumption was initially lower in methamphetamine pre-exposed vs. not pre-exposed rats. However, during the second week following abstinence, consumption was significantly higher in phase shifted rats of the methamphetamine pre-exposed group compared to all other groups. Conclusions These data reveal an effect of circadian rhythm disturbance on methamphetamine consumption, and suggest that dysregulation of the circadian system be considered in the etiology of relapse and addiction. PMID:25543849

Rhabdomyolysis in a Patient Taking Both Oxandrolone for Bodybuilding and Methamphetamine.

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Krzyzak, Michael; Elangovan, Natarajan

2017-11-13

Nonprescription drug use is increasingly prevalent in the United States. We report a case of a 31-year-old male who presented with hallucinations and was found to have rhabdomyolysis. He was consuming oxandrolone for six weeks and ingested methamphetamine the night prior to presentation. With supportive treatment, including intravenous hydration, the patient's mental status returned to baseline and rhabdomyolysis resolved. Our case illustrates the need to understand the interaction between different illicit substances. More research needs to be done to further understand the reactions between different medications as patients consume different combinations of substances.

Cannabinoid Receptors Mediate Methamphetamine Induction of High Frequency Gamma Oscillations in the Nucleus Accumbens

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Morra, Joshua T.; Glick, Stanley D.; Cheer, Joseph F.

2012-01-01

Patients suffering from amphetamine---induced psychosis display repetitive behaviors, partially alleviated by antipsychotics, which are reminiscent of rodent stereotypies. Due to recent evidence implicating endocannabinoid involvement in brain disorders, including psychosis, we studied the effects of endocannabinoid signaling on neuronal oscillations of rats exhibiting methamphetamine stereotypy. Neuronal network oscillations were recorded with multiple single electrode arrays aimed at the nucleus accumbens of freely moving rats. During the experiments, animals were dosed intravenously with the CB1 receptor antagonist rimonabant (0.3 mg/kg) or vehicle followed by an ascending dose regimen of methamphetamine (0.01, 0.1, 1, and 3 mg/kg; cumulative dosing). The effects of drug administration on stereotypy and local gamma oscillations were evaluated. Methamphetamine treatment significantly increased high frequency gamma oscillations (~ 80 Hz). Entrainment of a subpopulation of nucleus accumbens neurons to high frequency gamma was associated with stereotypy encoding in putative fast-spiking interneurons, but not in putative medium spiny neurons. The observed ability of methamphetamine to induce both stereotypy and high frequency gamma power was potently disrupted following CB1 receptor blockade. The present data suggest that CB1 receptor-dependent mechanisms are recruited by methamphetamine to modify striatal interneuron oscillations that accompany changes in psychomotor state, further supporting the link between endocannabinoids and schizophrenia spectrum disorders. PMID:22609048

Mind Over Matter: Methamphetamine

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... Teaching Guide and Series / Methamphetamine Mind Over Matter: Methamphetamine (Meth) Print Order Free Publication in: English Spanish ... paranoia, aggressiveness, and hallucinations. The Brain's Response to Methamphetamine Hi, my name's Sara Bellum. Welcome to my ...

The effect of methamphetamine and heroin price on polydrug use: A behavioural economics analysis in Sydney, Australia.

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Chalmers, Jenny; Bradford, Deborah; Jones, Craig

2010-09-01

A key aim of supply-side drug law enforcement is to reduce drug use by increasing the retail price of drugs. Since most illicit drug users are polydrug users the effectiveness of this strategy depends on the extent to which drug users reduce their overall consumption of drugs. The literature shows that drug users do reduce their consumption of a drug when its price increases. However the extent of that decrease and the implications for the use of other drugs vary across studies. A sample of 101 Australian methamphetamine users was surveyed using a behavioural economics approach. Participants were given a hypothetical fixed drug budget, presented with a range of drug price lists and asked how many units of each drug they would purchase. Methamphetamine and heroin prices were varied independently across trials. While demand for both methamphetamine and heroin was found to be price elastic, elasticity estimates were influenced by the nature of participants' drug dependence. The group least responsive to changes in methamphetamine price were those dependent only on methamphetamine, while the group most responsive were dependent only on heroin. Similar findings emerged in relation to changes in heroin price. Cross-price elasticity analysis showed limited substitution into other drugs as the price of methamphetamine increased. In contrast, for heroin, there was significant substitution into pharmaceutical opioids and to a lesser extent, benzodiazepines and methamphetamine. However, for the most part, the decreases in methamphetamine or heroin consumption outweighed any substitution into other drugs. The reduction in overall drug consumption and expenditure in response to price increases in heroin and methamphetamine observed in this sample lend support to supply-side enforcement strategies that aim to increase retail drug price. Notably, this analysis highlights the importance of accounting for the nature of users' drug dependence in estimating price responsiveness

Methamphetamine Use in Club Subcultures

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Kelly, Brian C.; LeClair, Amy; Parsons, Jeffrey T.

2014-01-01

In recent decades, methamphetamine developed a peculiar geographic distribution in the United States, with limited diffusion in the Northeast. While use within gay clubs received attention, methamphetamine in club subcultures more broadly remains less clear. Using quantitative and qualitative data, we provide a descriptive assessment of methamphetamine use in club subcultures. Methamphetamine use in club subcultures often has instrumental purposes. The context of initiation into methamphetamine use and its close connection to cocaine shape later patterns of use. Viewing meth solely as a gay party drug misses a significant part of the population and may misguide public health strategies to reduce methamphetamine use in the Northeast. PMID:23848380

Boundary Conditions of Methamphetamine Craving

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Lopez, Richard B.; Onyemekwu, Chukwudi; Hart, Carl L.; Ochsner, Kevin N.; Kober, Hedy

2015-01-01

Methamphetamine use has increased significantly and become a global health concern. Craving is known to predict methamphetamine use and relapse following abstinence. Some have suggested that cravings are automatic, generalized, and uncontrollable, but experimental work addressing these claims is lacking. In two exploratory studies we tested the boundary conditions of methamphetamine craving by asking: (1) is craving specific to users’ preferred route of administration? and (2) can craving be regulated by cognitive strategies? Two groups of methamphetamine users were recruited. In Study 1, participants were grouped by their preferred route of administration (intranasal vs. smoking), and rated their craving in response to photographs and movies depicting methamphetamine use (via the intranasal vs. smoking route). In Study 2, methamphetamine smokers implemented cognitive regulation strategies while viewing photographs depicting methamphetamine smoking. Strategies involved either focusing on the positive aspects of smoking methamphetamine or the negative consequences of doing so – the latter strategy based on treatment protocols for addiction. In Study 1, we found a significant interaction between group and route of administration, such that participants who preferred to smoke methamphetamine reported significantly stronger craving for smoking stimuli, whereas those who preferred the intranasal route reported stronger craving for intranasal stimuli. In Study 2, participants reported significantly lower craving when focusing on the negative consequences associated with methamphetamine use. Taken together, these findings suggest that strength of craving for methamphetamine is moderated by users’ route of administration and can be reduced by cognitive strategies. This has important theoretical, methodological, and clinical implications. PMID:26302338

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

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Nishimura, Tetsuya; Takahata, Kazue; Kosugi, Yuri; Tanabe, Takaaki; Muraoka, Shizuko

2017-01-01

l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1?10?mg/kg. However, plasma pharmacokinetic parameters of 10?mg/kg l-methamphetamine were ?tenfold those of 1?mg/kg d-methamphetamine. These resul...

Inhibiting effects of rhynchophylline on methamphetamine-dependent zebrafish are related with the expression of tyrosine hydroxylase (TH).

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Zhu, Chen; Liu, Wei; Luo, Chaohua; Liu, Yi; Li, Chan; Fang, Miao; Lin, Yingbo; Ou, Jinying; Chen, Minting; Zhu, Daoqi; Yung, Ken Kin-Lam; Mo, Zhixian

2017-03-01

In this study, to study the effect of rhynchophylline on TH in midbrain of methamphetamine-induced conditioned place preference (CPP) adult zebrafish, place preference adult zebrafish models were established by methamphetamine (40μg/g) and the expression of TH was observed by immunohistochemistry technique and Western blot. Ketamine (150μg/g), high dose of rhynchophylline (100μg/g) group can significantly reduce the place preference; immunohistochemistry results showed that the number of TH-positive neurons in midbrain was increased in the methamphetamine model group, whereas less TH-positive neurons were found in the ketamine group and high dosage rhynchophylline group. Western blot results showed that the expression of TH protein was significantly increased in the model group, whereas less expression was found in the ketamine group, high dosage rhynchophylline group. Our data pointed out that TH plays an important role in the formation of methamphetamine-induced place preference in adult zebrafish. Rhynchophylline reversed the expression of TH in the midbrain demonstrates the potential effect of mediates methamphetamine induced rewarding effect. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of adolescent methamphetamine exposure

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Jordan M Buck

2015-04-01

Full Text Available Methamphetamine use among adolescents is a significant social and public health concern. Despite increased awareness of methamphetamine use among younger people, relatively little research has examined the effects of adolescent methamphetamine use compared to adult use. Thus much remains to be learned about how methamphetamine alters adolescent brain function and behavior. In this article we review recent trends in adolescent methamphetamine use and data examining the effects of adolescent methamphetamine use on the dopaminergic system and behavior in humans and animal models. Future research is warranted to expand our understanding of the effects of adolescent methamphetamine exposure and how those effects differ from those seen in adults.

Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys

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Banks, Matthew L.; Smith, Douglas A.; Kisor, David F.; Poklis, Justin L.

2015-01-01

Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphet...

Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

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Mariana Raineri

Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

Development and validation of a Thai stressful life events rating scale for patients with a diagnosis of schizophrenic methamphetamine abuse

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Ek-uma Imkome

2017-04-01

Full Text Available This study aimed to psychometrically test a Thai Stressful Life Events Rating Scale (TSLERS. Factor analysis was done on data collected from 313 patients with schizophrenia and methamphetamine abuse in Thailand from April to May, 2015. Results identified the following problems impacting physical and mental health: social relationship and social concerns, money, family life, life security, and career. Evaluation of the psychometric scale properties demonstrated acceptable validity and reliability. TSLERS provided scientific and empirical data about stressful life events of patients with schizophrenia and methamphetamine abuse, and was suitable for stress detection and suggesting further innovations.

Methamphetamine Use and Pulmonary Hypertension

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... 03-13T18:35:19+00:00 PH and Methamphetamine Use Print PH and Methamphetamine Use Brochure (PDF) ... me if I had ever used stimulants like methamphetamines (speed). Why am I being asked this? Research ...

Monitoring the prevalence of methamphetamine-related ...

African Journals Online (AJOL)

Objective: This study aimed to determine a demographic profile of methamphetamine (MA)-related admissions to major psychiatric services in Cape Town, obtain a substance use profile from admitted patients, a profile of common MA-related symptoms encountered during the assessment of the patients presenting with ...

Methamphetamine/Dextroamphetamine and Pregnancy

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Methamphetamine | Dextroamphetamine In every pregnancy, a woman starts out with a 3-5% chance of having a ... risk. This sheet talks about whether exposure to methamphetamine or dextroamphetamine may increase the risk for birth ...

New Approaches to the Methamphetamine Epidemic

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Zusman, Mara B.

2004-01-01

Methamphetamine abuse has become an epidemic in the United States. As methamphetamine becomes increasingly available, more and more people are trying – and becoming addicted to – this potent drug. But although methamphetamine is made using over-the-counter (OTC) drugs containing pseudoephedrine, shifting OTC drugs containing pseudoephedrine to prescription status is not the solution to the methamphetamine crisis. Rather, society must adopt a comprehensive...

Methamphetamine and the expanding complications of amphetamines.

OpenAIRE

Albertson, T E; Derlet, R W; Van Hoozen, B E

1999-01-01

During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse.

21 CFR 862.3610 - Methamphetamine test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methamphetamine test system. 862.3610 Section 862....3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine...

The Neurobiology of Methamphetamine Induced Psychosis

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Jennifer Hsin-Wen Hsieh

2014-07-01

Full Text Available Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support methamphetamine induced psychosis as a model for schizophrenia.

Differences in Clinical Features of Methamphetamine Users with Persistent Psychosis and Patients with Schizophrenia.

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Wang, Liang-Jen; Lin, Shih-Ku; Chen, Yi-Chih; Huang, Ming-Chyi; Chen, Tzu-Ting; Ree, Shao-Chun; Chen, Chih-Ken

Methamphetamine exerts neurotoxic effects and elicits psychotic symptoms. This study attempted to compare clinical differences between methamphetamine users with persistent psychosis (MAP) and patients with schizophrenia. In addition, we examined the discrimination validity by using symptom clusters to differentiate between MAP and schizophrenia. We enrolled 53 MAP patients and 53 patients with schizophrenia. The psychopathology of participants was assessed using the Chinese version of the Diagnostic Interview for Genetic Studies and the 18-item Brief Psychiatric Rating Scale. Logistic regression was used to examine the predicted probability scores of different symptom combinations on discriminating between MAP and schizophrenia. The receiver operating characteristic (ROC) analyses and area under the curve (AUC) were further applied to examine the discrimination validity of the predicted probability scores on differentiating between MAP and schizophrenia. We found that MAP and schizophrenia demonstrated similar patterns of delusions. Compared to patients with schizophrenia, MAP experienced significantly higher proportions of visual hallucinations and of somatic or tactile hallucinations. However, MAP exhibited significantly lower severity in conceptual disorganization, mannerism/posturing, blunted affect, emotional withdrawal, and motor retardation compared to patients with schizophrenia. The ROC analysis showed that a predicted probability score combining the aforementioned 7 items of symptoms could significantly differentiate between MAP and schizophrenia (AUC = 0.77). Findings in the current study suggest that nuanced differences might exist in the clinical presentation of secondary psychosis (MAP) and primary psychosis (schizophrenia). Combining the symptoms as a whole may help with differential diagnosis for MAP and schizophrenia. © 2016 S. Karger AG, Basel.

[Identification of Methamphetamine Abuse and Selegiline Use： Chiral Analysis of Methamphetamine and Amphetamine in Urine].

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Xiang, P; Bu, J; Qiao, Z; Zhuo, X Y; Wu, H J; Shen, M

2017-12-01

To study the content variation of selegiline and its metabolites in urine, and based on actual cases, to explore the feasibility for the identification of methamphetamine abuse and selegiline use by chiral analysis. The urine samples were tested by chiral separation and LC-MS/MS method using CHIROBIOTIC™ V2 chiral liquid chromatography column. The chiral analysis of methamphetamine and amphetamine were performed on the urine samples from volunteers of selegiline use and drug addicts whom suspected taking selegiline. After 5 mg oral administration, the positive test time of selegiline in urine was less than 7 h. The mass concentrations of R（-）-methamphetamine and R（-）-amphetamine in urine peaked at 7 h which were 0.86 μg/mL and 0.18 μg/mL and couldn't be detected after 80 h and 168 h, respectively. The sources of methamphetamine and amphetamine in the urine from the drug addicts whom suspected taking selegiline were analysed successfully by present method. The chiral analysis of methamphetamine and amphetamine, and the determination of selegiline's metabolites can be used to distinguish methamphetamine abuse from selegiline use. Copyright© by the Editorial Department of Journal of Forensic Medicine

Emotion dysregulation and amygdala dopamine D2-type receptor availability in methamphetamine users.

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Okita, Kyoji; Ghahremani, Dara G; Payer, Doris E; Robertson, Chelsea L; Dean, Andy C; Mandelkern, Mark A; London, Edythe D

2016-04-01

Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM-IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala. Ninety-four methamphetamine-using and 102 healthy-control subjects completed the Difficulties in Emotion Regulation Scale (DERS); 33 of those who used methamphetamine completed the Addiction Severity Index (ASI). A subset of 27 methamphetamine-group and 20 control-group subjects completed positron emission tomography with [(18)F]fallypride to assay amygdala D2-type dopamine receptor availability, measured as binding potential (BPND). The methamphetamine group scored higher than the control group on the DERS total score (pmethamphetamine group. The DERS total score was positively correlated with amygdala BPND in both groups and the combined group of participants (combined: r=0.331, p=0.02), and the groups did not differ in this relationship. These findings highlight problems with emotion regulation linked to methamphetamine use, possibly contributing to personal and interpersonal behavioral problems. They also suggest that D2-type dopamine receptors in the amygdala contribute to emotion regulation in both healthy and methamphetamine-using subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function.

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Kesby, James P; Najera, Julia A; Romoli, Benedetto; Fang, Yiding; Basova, Liana; Birmingham, Amanda; Marcondes, Maria Cecilia G; Dulcis, Davide; Semenova, Svetlana

2017-10-01

Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period. Dopamine function in the nucleus accumbens (Acb) was determined using high performance liquid chromatography. Expression of dopamine and/or adenosine A receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR and immunohistochemistry analyses. Microarrays with pathway analyses assessed dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter switching of a reserve pool of non-dopaminergic neurons to a dopaminergic phenotype in the ventral tegmental area (VTA) was determined by immunohistochemistry and quantified with stereology. TAT expression enhanced methamphetamine-induced sensitization. TAT expression alone decreased striatal dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing ADORA2A receptors expression. Moreover, TAT expression combined with methamphetamine exposure was associated with increased adenosine A receptors (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA. TAT expression and methamphetamine exposure induced microglia activation with the largest effect after combined exposure. Our findings suggest that dopamine-adenosine receptor interactions and reserve pool neuronal recruitment may represent potential targets to develop new treatments for

Neuroadaptations in the dentate gyrus following contextual cued reinstatement of methamphetamine seeking.

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Takashima, Yoshio; Fannon, McKenzie J; Galinato, Melissa H; Steiner, Noah L; An, Michelle; Zemljic-Harpf, Alice E; Somkuwar, Sucharita S; Head, Brian P; Mandyam, Chitra D

2018-02-13

Abstinence from unregulated methamphetamine self-administration increases hippocampal dependent, context-driven reinstatement of methamphetamine seeking. The current study tested the hypothesis that alterations in the functional properties of granule cell neurons (GCNs) in the dentate gyrus (DG) of the hippocampus in concert with altered expression of synaptic plasticity-related proteins and ultrastructural changes in the DG are associated with enhanced context-driven methamphetamine-seeking behavior. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naïve (controls) and methamphetamine experienced animals (during acute withdrawal, during abstinence, after extinction and after reinstatement). Spontaneous excitatory postsynaptic currents (sEPSCs) and intrinsic excitability were recorded from GCNs. Reinstatement of methamphetamine seeking increased sEPSC frequency and produced larger amplitude responses in GCNs compared to controls and all other groups. Reinstatement of methamphetamine seeking reduced spiking capability in GCNs compared to controls, and all other groups, as indicated by reduced intrinsic spiking elicited by increasing current injections, membrane resistance and fast after hyperpolarization. In rats that reinstated methamphetamine seeking, these altered electrophysiological properties of GCNs were associated with enhanced expression of Fos, GluN2A subunits and PSD95 and reduced expression of GABA A subunits in the DG and enhanced expression of synaptic PSD in the molecular layer. The alterations in functional properties of GCNs and plasticity related proteins in the DG paralleled with no changes in structure of microglial cells in the DG. Taken together, our results demonstrate that enhanced reinstatement of methamphetamine seeking results in alterations in intrinsic spiking and spontaneous glutamatergic synaptic transmission in the GCNs and concomitant increases in neuronal activation of GCNs, and expression

Irreversible brain damage caused by methamphetamine

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Sebastian Moeller

2016-03-01

Full Text Available Methamphetamine is an addictive scene substance usage of which is increasing rapidly. While methamphetamine often causes neuropsychiatric symptoms like anxiety, psychosis and hallucinations, reports of structural ongoing cerebral alterations are rare. We here report a case of this kind of damage caused through methamphetamine use.

Nasal Septum Perforation due to Methamphetamine abuse

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Mehdi Bakhshaee

2012-07-01

Full Text Available Introduction: Spontaneous Perforation of the nasal septum is an uncommon condition. Nasal inhalation of substances such as cocaine has long been linked to this Perforation. Case Report: This report describes the case of a 46-year-old woman who was addicted to methamphetamine and who presented with perforation of the nasal septum.This is the first reported case of nasal septal necrosis linked to nasal inhalation of methamphetamine. Conclusions: Patient history and assurance regardingillegal drug consumption and abuse is a key point for fast and accurate diagnosis. The pathophysiology of drug-induced sinunasal disease and a review of the literature are also presented.

Functional interactions of HIV-infection and methamphetamine dependence during motor programming.

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Archibald, Sarah L; Jacobson, Mark W; Fennema-Notestine, Christine; Ogasawara, Miki; Woods, Steven P; Letendre, Scott; Grant, Igor; Jernigan, Terry L

2012-04-30

Methamphetamine (METH) dependence is frequently comorbid with HIV infection and both have been linked to alterations of brain structure and function. In a previous study, we showed that the brain volume loss characteristic of HIV infection contrasts with METH-related volume increases in striatum and parietal cortex, suggesting distinct neurobiological responses to HIV and METH (Jernigan et al., 2005). Functional magnetic resonance imaging (fMRI) has the potential to reveal functional interactions between the effects of HIV and METH. In the present study, 50 participants were studied in four groups: an HIV+ group, a recently METH-dependent group, a dually affected group, and a group of unaffected community comparison subjects. An fMRI paradigm consisting of motor sequencing tasks of varying levels of complexity was administered to examine blood oxygenation level dependent (BOLD) changes. Within all groups, activity increased significantly with increasing task complexity in large clusters within sensorimotor and parietal cortex, basal ganglia, cerebellum, and cingulate. The task complexity effect was regressed on HIV status, METH status, and the HIV×METH interaction term in a simultaneous multiple regression. HIV was associated with less complexity-related activation in striatum, whereas METH was associated with less complexity-related activation in parietal regions. Significant interaction effects were observed in both cortical and subcortical regions; and, contrary to expectations, the complexity-related activation was less aberrant in dually affected than in single risk participants, in spite of comparable levels of neurocognitive impairment among the clinical groups. Thus, HIV and METH dependence, perhaps through their effects on dopaminergic systems, may have opposing functional effects on neural circuits involved in motor programming. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

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Manning, Elizabeth E; van den Buuse, Maarten

2016-05-15

Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Associations Between Family History of Substance Use, Childhood Trauma, and Age of First Drug Use in Persons With Methamphetamine Dependence.

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Svingen, Leah; Dykstra, Rita E; Simpson, Jamie L; Jaffe, Anna E; Bevins, Rick A; Carlo, Gustavo; DiLillo, David; Grant, Kathleen M

2016-01-01

The current study examined the association among family history of substance use problems, childhood maltreatment, and age of first drug use in a sample of men and women seeking treatment for methamphetamine dependence. Various forms of childhood maltreatment were considered as mediators of the association between family history of substance use problems and age of first drug use. Participants (N = 99, 40% women, mean age 33) who were under treatment for methamphetamine dependence completed a baseline interview that obtained demographic information, past substance use by participants, history of drug/alcohol problems in their family of origin, and age at first use of any drug (excluding alcohol and tobacco). The Early Trauma Inventory Self-Report-Short Form was used to assess child maltreatment experiences before the age of 18. Family history of substance use problems and childhood physical (but not emotional or sexual) trauma significantly predicted age of first drug use. Further, childhood physical trauma mediated the association between family history of substance use problems and age of first drug use. These findings suggest that the experience of childhood physical abuse may be an important mechanism through which family history of substance use is associated with an earlier age of first drug use.

Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase

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Engelmann, Alexander J.; Aparicio, Mark B.; Kim, Airee; Sobieraj, Jeffery C.; Yuan, Clara J.; Grant, Yanabel

2013-01-01

We investigated whether prior exposure to chronic wheel running (WR) alters maladaptive patterns of excessive and escalating methamphetamine intake under extended access conditions, and intravenous methamphetamine self-administration-induced neurotoxicity. Adult rats were given access to WR or no wheel (sedentary) in their home cage for 6 weeks. A set of WR rats were injected with 5-bromo-2′-deoxyuridine (BrdU) to determine WR-induced changes in proliferation (2-h old) and survival (28-day old) of hippocampal progenitors. Another set of WR rats were withdrawn (WRw) or continued (WRc) to have access to running wheels in their home cages during self-administration days. Following self-administration [6 h/day], rats were tested on the progressive ratio (PR) schedule. Following PR, BrdU was injected to determine levels of proliferating progenitors (2-h old). WRc rats self-administered significantly less methamphetamine than sedentary rats during acquisition and escalation sessions, and demonstrated reduced motivation for methamphetamine seeking. Methamphetamine reduced daily running activity of WRc rats compared with that of pre-methamphetamine days. WRw rats self-administered significantly more methamphetamine than sedentary rats during acquisition, an effect that was not observed during escalation and PR sessions. WR-induced beneficial effects on methamphetamine self-administration were not attributable to neuroplasticity effects in the hippocampus and medial prefrontal cortex, but were attributable to WR-induced inhibition of methamphetamine-induced increases in the number of neuronal nitric oxide synthase expressing neurons and apoptosis in the nucleus accumbens shell. Our results demonstrate that WR prevents methamphetamine-induced damage to forebrain neurons to provide a beneficial effect on drug-taking behavior. Importantly, WR-induced neuroprotective effects are transient and continued WR activity is necessary to prevent compulsive methamphetamine intake

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

OpenAIRE

McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-01-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered ...

Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment.

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Robertson, Chelsea L; Ishibashi, Kenji; Chudzynski, Joy; Mooney, Larissa J; Rawson, Richard A; Dolezal, Brett A; Cooper, Christopher B; Brown, Amira K; Mandelkern, Mark A; London, Edythe D

2016-05-01

Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

Differences in the symptom profile of methamphetamine-related psychosis and primary psychotic disorders.

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McKetin, Rebecca; Baker, Amanda L; Dawe, Sharon; Voce, Alexandra; Lubman, Dan I

2017-05-01

We examined the lifetime experience of hallucinations and delusions associated with transient methamphetamine-related psychosis (MAP), persistent MAP and primary psychosis among a cohort of dependent methamphetamine users. Participants were classified as having (a) no current psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient MAP, n=85); (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent MAP, n=37), or (d) meeting DSM-IV criteria for lifetime schizophrenia or mania (primary psychosis, n=52). Current psychotic symptoms were classified as a score of 4 or more on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content in the past month. Lifetime psychotic diagnoses and symptoms were assessed using the Composite International Diagnostic Interview. Transient MAP was associated with persecutory delusions and tactile hallucinations (compared to the no symptom group). Persistent MAP was additionally associated with delusions of reference, thought interference and complex auditory, visual, olfactory and tactile hallucinations, while primary psychosis was also associated with delusions of thought projection, erotomania and passivity. The presence of non-persecutory delusions and hallucinations across various modalities is a marker for persistent MAP or primary psychosis in people who use methamphetamine. Copyright © 2017. Published by Elsevier B.V.

Methamphetamine

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... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Crystal in Iran: Methamphetamine or Heroin Kerack

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Zahra Alam Mehrjerdi

2013-03-01

Full Text Available In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications.

Similarity and Difference in Drug Addiction Process Between Heroin- and Methamphetamine-Dependent Users.

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Wang, Ziyun; Li, Wei-Xiu; Zhi-Min, Liu

2017-03-21

This study aimed to compare the drug addiction process between Chinese heroin- and methamphetamine (MA)-dependent users via a modified 4-stage addiction model (experimentation, occasional use, regular use, and compulsive use). A descriptive study was conducted among 683 eligible participants. In the statistical analysis, we selected 340 heroin- and 295 MA-dependent users without illicit drug use prior to onset of heroin or MA use. The addiction process of heroin-dependent users was shorter than that of MA-dependent users, with shorter transitions from the onset of drug-use to the first drug craving (19.5 vs. 50.0 days), regular use (30.0 vs. 60.0 days), and compulsive use (50.0 vs. 85.0 days). However, no significant differences in the addiction process were observed in frequency of drug administration, except that heroin users reported more administrations of the drug (20.0 vs. 15.0) before progressing to the stage of compulsive drug use. A larger proportion of regular heroin users progressed to use illicit drugs recklessly than did MA users. Most heroin and MA users reported psychological dependence as their primary motivation for compulsive drug use, but more heroin users selected uncomfortable symptoms upon ceasing drug use as further reason to continue. Our results suggest that typical heroin and MA users may experience a similar four-stage addiction process, but MA users might undergo a longer addiction process (in days). More research is necessary to further explore factors influencing the drug addiction process.

Is an Abnormal ECG Just the Tip of the ICE-berg? Examining the Utility of Electrocardiography in Detecting Methamphetamine-Induced Cardiac Pathology.

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Paratz, Elizabeth D; Zhao, Jessie; Sherwen, Amanda K; Scarlato, Rose-Marie; MacIsaac, Andrew I

2017-07-01

Methamphetamine use is escalating in Australia and New Zealand, with increasing emergency department attendance and mortality. Cardiac complications play a large role in methamphetamine-related mortality, and it would be informative to assess the frequency of abnormal electrocardiograms (ECGs) amongst methamphetamine users. To determine the frequency and severity of ECG abnormalities amongst methamphetamine users compared to a control group. We conducted a retrospective cohort analysis on 212 patients admitted to a tertiary hospital (106 patients with methamphetamine use, 106 age and gender-matched control patients). Electrocardiograms were analysed according to American College of Cardiology guidelines. Mean age was 33.4 years, with 73.6% male gender, with no significant differences between groups in smoking status, ECG indication, or coronary angiography rates. Methamphetamine users were more likely to have psychiatric admissions (22.6% vs 1.9%, pmethamphetamine users, particularly tachyarrhythmias (38.7% vs 26.4%, pmethamphetamine users than age and gender-matched controls. Due to the high frequency of abnormalities, ECGs should be performed in all methamphetamine users who present to hospital. Methamphetamine users with abnormal ECGs should undergo further cardiac investigations. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Methamphetamine initiation among HIV-positive gay and bisexual men

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Nakamura, Nadine; Semple, Shirley J.; Strathdee, Steffanie A.; Patterson, Thomas L.

2009-01-01

This study describes factors associated with methamphetamine initiation in a racially diverse sample of 340 methamphetamine-using, HIV-positive gay and bisexual men. A factor analysis was conducted on reasons for initiation, and four factors were identified: to party, to cope, for energy, and to improve self-esteem. Methamphetamine to party accounted for more than one-third of the variance in the factor analysis. Methamphetamine to cope captured almost 9% of the variance, methamphetamine for ...

Methamphetamine and MDMA: ‘Safe’ drugs of abuse

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Allana M. Krolikowski

2014-03-01

Full Text Available Methamphetamine and MDMA have been called safe drugs of abuse. Worldwide there is an increased consumption of these drugs, which has become a focus of research in South Africa. As the number of methamphetamine users has increased in many African countries, it is essential that emergency care practitioners are able to diagnose and manage intoxication with methamphetamine, MDMA, and other derivatives. The most common presentations include restlessness, agitation, hypertension, tachycardia, and headache while hyperthermia, hyponatraemia, and rhabdomyolysis are among the most common serious complications. Most deaths are secondary to hyperthermia complicated by multiple organ failure. A number of laboratory analyses should be obtained if locally available. We provide a review of the current recommended general and specific management approaches. Benzodiazepines are the first line therapy for hyperthermia, agitation, critical hypertension, and seizures. Patients with serious complications are best managed in an intensive care unit if available. Emergency centres should create protocols and/or further train staff in the recognition and management of intoxication with these ‘not so safe’ drugs.

Correlation of abdominopelvic computed tomography with clinical manifestations in methamphetamine body stuffers.

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Bahrami-Motlagh, Hooman; Hassanian-Moghaddam, Hossein; Zamini, Hedieh; Zamani, Nasim; Gachkar, Latif

2018-02-01

Little is known about methamphetamine body stuffers and correlation of clinical manifestations with imaging studies. Current study was done to determine abdominopelvic computed tomography findings and clinical manifestations in methamphetamine body stuffers. In an IRB-approved routine data base study, demographic characteristics, clinical findings, and CT results of 70 methamphetamine body stuffers were retrieved. According to the clinical manifestations, the patients were categorized into either benign- or severe-outcome group. Also, they were determined to have positive or negative CT results. In the group with positive results, number and place of the baggies were determined, as well. Results of the CT were compared between the two groups. Almost 43% of the patients had positive abdominopelvic CT results. Mean density of the packs was 176.2 ± 152.7 Hounsfield unit. Based on the clinical grounds, 57% of the patients were in the benign- and 33% were in the severe-outcome group. In the benign group, 45% of the patients had positive CTs while in the severe-risk group, this was 40% (p > 0.05). Except variables defined as severe outcome (seizure, intubation, creatinine level, aspartate aminotransferase level, creatine phosphokinase and troponin level), agitation, on-arrival pulse rate, lactate dehydrogenase, bicarbonate, base excess, loss of consciousness and hospitalization period were correlating factors. But in regression analysis, we could not find a significant variable that prognosticate severe outcome. It seems that there is no relationship between the CT findings and clinical manifestations of the methamphetamine body stuffers. Severe outcomes may be observed even in the face of negative CTs.

Correlates of trading sex for methamphetamine in a sample of HIV-negative heterosexual methamphetamine users.

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Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; Patterson, Thomas L

2011-01-01

While many studies have examined correlates of trading sex for money, few have examined factors associated with exclusive trading of sex for drugs. We identified sociodemographic, behavioral, and psychological correlates of trading sex for methamphetamine in a sample of HIV-negative heterosexual men and women who were enrolled in a sexual risk reduction intervention in San Diego, California. Of 342 participants, 26% overall (21% of males and 31% of females) reported trading sex for methamphetamine in the past two months. Multiple logistic regression analysis revealed that recently trading sex for methamphetamine was independently associated with being female, homeless, binging on methamphetamine, sexual victimization in the past two months, engaging in anal sex 24 or more times in the past two months, and higher sexual compulsivity scores. Effective interventions for this high-risk population should consider gender-focused counseling for sexual abuse, motivational enhancement therapy, social-cognitive skills training, as well as enhanced access and utilization of social services, including drug treatment.

Involvement of PUMA in pericyte migration induced by methamphetamine.

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Zhang, Yanhong; Zhang, Yuan; Bai, Ying; Chao, Jie; Hu, Gang; Chen, Xufeng; Yao, Honghong

2017-07-01

Mounting evidence indicates that methamphetamine causes blood-brain barrier damage, with emphasis on endothelial cells. The role of pericytes in methamphetamine-induced BBB damage remains unknown. Our study demonstrated that methamphetamine increased the migration of pericytes from the endothelial basement membrane. However, the detailed mechanisms underlying this process remain poorly understood. Thus, we examined the molecular mechanisms involved in methamphetamine-induced pericyte migration. The results showed that exposure of C3H/10T1/2 cells and HBVPs to methamphetamine increased PUMA expression via activation of the sigma-1 receptor, MAPK and Akt/PI3K pathways. Moreover, methamphetamine treatment resulted in the increased migration of C3H/10T1/2 cells and HBVPs. Knockdown of PUMA in pericytes transduced with PUMA siRNA attenuated the methamphetamine-induced increase in cell migration through attenuation of integrin and tyrosine kinase mechanisms, implicating a role of PUMA in the migration of C3H/10T1/2 cells and HBVPs. This study has demonstrated that methamphetamine-mediated pericytes migration involves PUMA up-regulation. Thus, targeted studies of PUMA could provide insights to facilitate the development of a potential therapeutic approach for alleviation of methamphetamine-induced pericyte migration. Copyright © 2017. Published by Elsevier Inc.

Methamphetamine Pills

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... Alzheimer’s disease. What are signs of use? Irritability/aggression Anxiety Nervousness Convulsions Insomnia Source : National Institute on Drug Abuse (NIDA) ; Drug Enforcement Agency (DEA) Related Drugs Methamphetamine ( ...

The mental health experiences and needs of methamphetamine ...

African Journals Online (AJOL)

Background. South Africa (SA) has a burgeoning problem of methamphetamine use, particularly in the Western Cape Province. Although methamphetamine has been associated with elevated psychological distress, there has been little examination of the mental health needs of out-of-treatment methamphetamine users in ...

Methamphetamine overdose

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... dialysis (kidney machine) Destruction of muscles, which can lead to amputation An extremely large methamphetamine overdose can cause death. Alternative Names Intoxication - amphetamines; Intoxication - uppers; Amphetamine intoxication; Uppers overdose; Overdose - ...

Melatonin in concentrated ethanol and ethanol alone attenuate methamphetamine-induced dopamine depletions in C57BL/6J mice.

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Yu, L; Cherng, C-F G; Chen, C

2002-12-01

The present study aimed to investigate the protective effects of melatonin, ethanol and temperature changes on methamphetamine-induced neurotoxicity in both sexes of mice. Mice exhibited a similar degree of striatal dopamine depletion when methamphetamine was administered during the light and dark cycles. Moreover, 10 mg/kg, but not 5 mg/kg, of methamphetamine, significantly increased body temperature even though dopamine depletions were observed following both doses. Melatonin (80 mg/kg) dissolved in 30% (v/v) ethanol and 30% ethanol alone exerted a moderate to full protection against methamphetamine-induced dopamine depletions in both sexes of mice, whereas the same dose of melatonin in 3% ethanol exerted no protective effect. Furthermore, ethanol attenuated methamphetamine-induced dopamine depletions in a dose-dependent manner with the exception of high efficacy of ethanol at low doses. Finally, the protective effects of ethanol were not blocked by bicuculline. Together, we conclude that ethanol may protect mice against methamphetamine-induced dopamine depletion probably via non-GABAA receptor activation.

Analysing pseudoephedrine/methamphetamine policy options in Australia using multi-criteria decision modelling.

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Manning, Matthew; Wong, Gabriel T W; Ransley, Janet; Smith, Christine

2016-06-01

In this paper we capture and synthesize the unique knowledge of experts so that choices regarding policy measures to address methamphetamine consumption and dependency in Australia can be strengthened. We examine perceptions of the: (1) influence of underlying factors that impact on the methamphetamine problem; (2) importance of various models of intervention that have the potential to affect the success of policies; and (3) efficacy of alternative pseudoephedrine policy options. We adopt a multi-criteria decision model to unpack factors that affect decisions made by experts and examine potential variations on weight/preference among groups. Seventy experts from five groups (i.e. academia (18.6%), government and policy (27.1%), health (18.6%), pharmaceutical (17.1%) and police (18.6%)) in Australia participated in the survey. Social characteristics are considered the most important underlying factor, prevention the most effective strategy and Project STOP the most preferred policy option with respect to reducing methamphetamine consumption and dependency in Australia. One-way repeated ANOVAs indicate a statistically significant difference with regards to the influence of underlying factors (F(2.3, 144.5)=11.256, pmethamphetamine consumption and dependency. Most experts support the use of preventative mechanisms to inhibit drug initiation and delayed drug uptake. Compared to other policies, Project STOP (which aims to disrupt the initial diversion of pseudoephedrine) appears to be a more preferable preventative mechanism to control the production and subsequent sale and use of methamphetamine. This regulatory civil law lever engages third parties in controlling drug-related crime. The literature supports third-party partnerships as it engages experts who have knowledge and expertise with respect to prevention and harm minimization. Copyright © 2016 Elsevier B.V. All rights reserved.

Designing and Evaluation of Reliability and Validity of Visual Cue-Induced Craving Assessment Task for Methamphetamine Smokers

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Hamed Ekhtiari

2010-08-01

Full Text Available A B S T R A C TIntroduction: Craving to methamphetamine is a significant health concern and exposure to methamphetamine cues in laboratory can induce craving. In this study, a task designing procedure for evaluating methamphetamine cue-induced craving in laboratory conditions is examined. Methods: First a series of visual cues which could induce craving was identified by 5 discussion sessions between expert clinicians and 10 methamphetamine smokers. Cues were categorized in 4 main clusters and photos were taken for each cue in studio, then 60 most evocative photos were selected and 10 neutral photos were added. In this phase, 50 subjects with methamphetamine dependence, had exposure to cues and rated craving intensity induced by the 72 cues (60 active evocative photos + 10 neutral photos on self report Visual Analogue Scale (ranging from 0-100. In this way, 50 photos with high levels of evocative potency (CICT 50 and 10 photos with the most evocative potency (CICT 10 were obtained and subsequently, the task was designed. Results: The task reliability (internal consistency was measured by Cronbach’s alpha which was 91% for (CICT 50 and 71% for (CICT 10. The most craving induced was reported for category Drug use procedure (66.27±30.32 and least report for category Cues associated with drug use (31.38±32.96. Difference in cue-induced craving in (CICT 50 and (CICT 10 were not associated with age, education, income, marital status, employment and sexual activity in the past 30 days prior to study entry. Family living condition was marginally correlated with higher scores in (CICT 50. Age of onset for (opioids, cocaine and methamphetamine was negatively correlated with (CICT 50 and (CICT 10 and age of first opiate use was negatively correlated with (CICT 50. Discussion: Cue-induced craving for methamphetamine may be reliably measured by tasks designed in laboratory and designed assessment tasks can be used in cue reactivity paradigm, and

The role of dopamine receptors in the neurotoxicity of methamphetamine.

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Ares-Santos, S; Granado, N; Moratalla, R

2013-05-01

Methamphetamine is a synthetic drug consumed by millions of users despite its neurotoxic effects in the brain, leading to loss of dopaminergic fibres and cell bodies. Moreover, clinical reports suggest that methamphetamine abusers are predisposed to Parkinson's disease. Therefore, it is important to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity. Dopamine receptors may be a plausible target to prevent this neurotoxicity. Genetic inactivation of dopamine D1 or D2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D1 receptor inactivation is due to blockade of hypothermia, reduced dopamine content and turnover and increased stored vesicular dopamine in D1R(-/-) mice. However, the neuroprotective impact of D2 receptor inactivation is partially dependent on an effect on body temperature, as well as on the blockade of dopamine reuptake by decreased dopamine transporter activity, which results in reduced intracytosolic dopamine levels in D2R(-/-) mice. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

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Kesby, James P.; Markou, Athina; Semenova, Svetlana

2014-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

Metabolic Precursors to Amphetamine and Methamphetamine.

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Cody, J D

1993-12-01

Analysis and interpretation of amphetamine results is a challenging process made difficult by a number of factors. One of the complications comes from determination of the origin of amphetamine or methamphetamine in a sample. Given the relatively rare occasions that either of these two drugs are prescribed, legal prescription of one of these drugs is seldom a reason for positive findings. A number of other precursor compounds are metabolized by the body to amphetamine or methamphetamine, many of which could be used for legitimate reasons. Fourteen different metabolic precursors of amphetamine or methamphetamine are included in this review. They are amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Medical use, metabolism, analysis, and interpretation are described to afford sufficient information to evaluate the possible involvement of these drugs in positive amphetamine or methamphetamine results. Copyright © 1993 Central Police University.

Domestic Violence in Methamphetamine Psychotic Users, Psychiatric Inpatients, and Healthy People: A Comparative Study

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Seyed Mohammad Rasoul Khalkhali

2016-11-01

Full Text Available Background: Domestic violence is a serious threat to the physical and mental health of women. The aim of the present study was to find and compare the frequency of domestic violence between methamphetamine users, patients with psychiatric disorders, and healthy people. Methods: In this analytical cross-sectional study, methamphetamine users (n=30 and patients with psychiatric disorders (n=30 were women whose husbands were hospitalized during 2014 in Shafa Psychiatric Hospital in Guilan. Diagnosis was done with DSMIV-TR. Healthy people (n=60 were women whose husbands had no primary or drug induced psychiatric disorder or addiction. CTS-2 test was used to evaluate violence. Results: The frequency of psychological, physical and sexual violence in the groups suffering from psychiatric disease and methamphetamine users was higher than the healthy group (P=0.001. We observed a direct correlation between the mean of psychological and physical violence in the three groups (r=0.9, P=0.001, (r=0.7, P=0.0001 and (r=0.53, P=0.005, respectively. Direct correlation between the psychological and physical violence was only observed in the healthy group (r=0.8, P=0.007. Conclusion: The results showed that methamphetamine users such as psychiatric patients are at increased risk of violence. Domestic violence screening of these patients is necessary. It seems that this substance is a new source of increasing domestic violence with more undesirable outcomes in Iran.

The profile of psychiatric symptoms exacerbated by methamphetamine use.

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McKetin, Rebecca; Dawe, Sharon; Burns, Richard A; Hides, Leanne; Kavanagh, David J; Teesson, Maree; McD Young, Ross; Voce, Alexandra; Saunders, John B

2016-04-01

Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, χ(2)(df1)=3.66, p=0.056). Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cognitive functions in methamphetamine induced psychosis compared to schizophrenia and normal subjects.

Directory of Open Access Journals (Sweden)

Zahra Ezzatpanah

2014-09-01

Full Text Available The purpose of this research was to study the cognitive functions in patients with methamphetamine-induced psychosis (MIP in comparison with schizophrenia patients and normal subjects.This was a cross-sectional study, 30 patients with MIP, 30 patients with schizophrenia and 30 normal individuals were selected via convenient sampling and were matched on age, sex and education. Wisconsin Cards Sorting, Stroop, Visual Search and Attention and Wechsler Memory Tests were used to assess the subjects.The study showed that patients with MIP and schizophrenia have more deficits in executive functions, selective attention, sustained attention and memory than normal subjects. There were no significant differences in cognitive functions between patients with MIP and schizophrenia except for visual search and attention that showed more impairment in patients with schizophrenia.Although, cognitive dysfunctions of patients with MIP are mostly similar to patients with schizophrenia, some differences seem to exist, especially in those functions that are not primarily dependent on frontal lobe.

Effect of methamphetamine on the pharmacokinetics of dextromethorphan and midazolam in rats.

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Dostalek, M; Hadasova, E; Hanesova, M; Pistovcakova, J; Sulcova, A; Jurica, J; Tomandl, J; Linhart, I

2005-01-01

Methamphetamine is the fourth most frequently reported compound associated with drug abuse on admission of patients to treatment centres after cocaine, heroin and marijuana. It is metabolized in the organism with a reaction that is catalyzed by cytochrome P450, mainly by the CYP2D and CYP3A subfamily, 4-hydroxyamphetamine and amphetamine being dominant metabolites. The present pharmacokinetic study was undertaken to investigate the possible influence of methamphetamine (10 mg/kg, i.p., once daily for six days) on the pharmacokinetics of dextromethorphane as a model substrate for rat cytochrome P-4502D2 and midazolam as a model substrate for CYP3A1/2. Animals received a single injection of dextromethorphane (10 mg/kg) or midazolam (5 mg/kg) in the tail vein 24 h after the last dose of methamphetamine or administration of placebo. The results of pharmacokinetic analysis showed a significantly increased rate of dextrorphane and 3-hydroxymorphinan formation, and a marked stimulatory effect of methamphetamine on CYP2D2 metabolic activity. Similarly, the kinetics of midazolam's metabolic conversion to hydroxy derivates of midazolam indicated a significant increase in CYP3A1/2 activity. The results showed that the administration of methamphetamine significantly stimulated the metabolic activity of CYP2D2 as well as that of CYP3A1/2. With regard to the high level of homology between human and rat CYP isoforms studied, the results may have a clinical impact on future pharmacotherapy for methamphetamine abuse.

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline.

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Mahoney, James J; Jackson, Brian J; Kalechstein, Ari D; De La Garza, Richard; Newton, Thomas F

2011-03-30

Abstinent methamphetamine (Meth) dependent individuals demonstrate poorer performance on tests sensitive to attention/information processing speed, learning and memory, and working memory when compared to non-Meth dependent individuals. The poorer performance on these tests may contribute to the morbidity associated with Meth-dependence. In light of this, we sought to determine the effects of acute, low-dose Meth administration on attention, working memory, and verbal learning and memory in 19 non-treatment seeking, Meth-dependent individuals. Participants were predominantly male (89%), Caucasian (63%), and cigarette smokers (63%). Following a four day, drug-free washout period, participants were given a single-blind intravenous infusion of saline, followed the next day by 30 mg of Meth. A battery of neurocognitive tasks was administered before and after each infusion, and performance on measures of accuracy and reaction time were compared between conditions. While acute Meth exposure did not affect test performance for the entire sample, participants who demonstrated relatively poor performance on these tests at baseline, identified using a median split on each test, showed significant improvement on measures of attention/information processing speed and working memory when administered Meth. Improved performance was seen on the following measures of working memory: choice reaction time task (p≤0.04), a 1-back task (p≤0.01), and a 2-back task (p≤0.04). In addition, those participants demonstrating high neurocognitive performance at baseline experienced similar or decreased performance following Meth exposure. These findings suggest that acute administration of Meth may temporarily improve Meth-associated neurocognitive performance in those individuals experiencing lower cognitive performance at baseline. As a result, stimulants may serve as a successful treatment for improving cognitive functioning in those Meth-dependent individuals experiencing

Optimization of a methamphetamine conjugate vaccine for antibody production in mice.

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Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael

2016-06-01

There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. Copyright © 2016 Elsevier B.V. All rights reserved.

Stroke and methamphetamine use in young adults: a review.

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Lappin, Julia M; Darke, Shane; Farrell, Michael

2017-12-01

Methamphetamine use and stroke are significant public health problems. Strokes among people aged below 45 years are much less common than in older age groups but have significant mortality and morbidity. Methamphetamine is a putative cause of strokes among younger people. A review of methamphetamine-related strokes was conducted. Bibliographic databases were searched until February 2017 for articles related to methamphetamine and stroke. Both haemorrhagic and ischaemic strokes were considered. Of 370 articles screened, 77 were selected for inclusion. There were 81 haemorrhagic and 17 ischaemic strokes reported in case reports and series. Both types were approximately twice as common in males. Route of administration associated with haemorrhagic stroke was typically oral or injecting, but for ischaemic stroke inhalation was most common. Haemorrhagic stroke was associated with vascular abnormalities in a third of cases. One quarter of individuals completely recovered, and a third died following haemorrhagic stroke. One-fifth completely recovered, and one-fifth died following ischaemic stroke. There is a preponderance of haemorrhagic strokes associated with methamphetamine use in young people, and methamphetamine-related stroke is associated with poor clinical outcomes. Mechanisms of methamphetamine-associated stroke include hypertension, vasculitis, direct vascular toxicity and vasospasm. In a period of rising worldwide methamphetamine use, the incidence of methamphetamine-related stroke will increase, with a consequent increase in the burden of disease contributed by such events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The vaporization enthalpy and vapor pressure of S (+)-methamphetamine at T = 298.15 K by correlation gas chromatography

International Nuclear Information System (INIS)

Thornton, Melissa; Gobble, Chase; Chickos, James

2014-01-01

Highlights: • The vaporization enthalpy of (d)-methamphetamine was measured. • The vapor pressure of (d)-methamphetamine as a function of temperature was evaluated. • The vapor pressure of 4-benzylpiperidine as a function of temperature was evaluated. - Abstract: The vaporization enthalpy and vapor pressure of S (+)-methamphetamine is evaluated by correlation-gas chromatography. A vaporization enthalpy of (58.7 ± 4.3) kJ · mol −1 and a vapor pressure, p = (38 ± 9) Pa has been obtained using a variety of secondary aliphatic amines as standards. In addition, equations describing the vapor pressure temperature dependence are provided for standards and S (+)-methamphetamine covering the temperature range from T = 298.15 K to the boiling temperature. Boiling temperatures are reproduced within an interval of 8 K or less

A Pilot Study of Creatine as a Novel Treatment for Depression in Methamphetamine Using Females

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Hellem, Tracy L.; Sung, Young-Hoon; Shi, Xian-Feng; Pett, Marjorie A.; Latendresse, Gwen; Morgan, Jubel; Huber, Rebekah S.; Kuykendall, Danielle; Lundberg, Kelly J.; Renshaw, Perry F.

2015-01-01

Objective Depression among methamphetamine users is more prevalent in females than males, but gender specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. Methods Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8 week open label trial of 5 grams of daily creatine monohydrate and of these 14, eleven females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. Results The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t(9) = 2.905, p creatine increased phosphocreatine levels. Also, a reduction in methamphetamine positive urine drug

Glutamatergic neurometabolites during early abstinence from chronic methamphetamine abuse.

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O'Neill, Joseph; Tobias, Marc C; Hudkins, Matthew; London, Edythe D

2014-10-31

The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon. We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a methamphetamine group of 44 adults who had chronically abused methamphetamine and a control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the methamphetamine group were studied as inpatients during the first week of abstinence from the drug and were not receiving treatment. In the methamphetamine group, small but significant (5-15%, Pright inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (Pabuse. The Beck Depression Inventory score was negatively correlated (Pright inferior frontal cortex. Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Histamine-dependent behavioral response to methamphetamine in 12-month-old male mice

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Acevedo, Summer F.; Raber, Jacob

2011-01-01

Methamphetamine (MA) use is a growing problem across the United States. Effects of MA include hyperactivity and increased anxiety. Using a mouse model system, we examined behavioral performance in the open field and elevated zero maze and shock-startle response of 12-month-old wild-type mice injected with MA once (1mg/kg) 30 min prior to behavioral testing. MA treatment resulted in behavioral sensitization in the open field, consistent with studies in younger mice. There was an increased activity in the elevated zero maze and an increased shock-startle response 30 and 60 min post-injection. Since histamine mediates some effects of MA in the brain, we assessed whether 12-month-old mice lacking histidine decarboxylase (Hdc−/−), the enzyme required to synthesize histamine, respond differently to MA than wild-type (Hdc+/+) mice. Compared to saline treatment, acute and repeated MA administration increased activity in the open field and measures of anxiety, though more so in Hdc−/− than Hdc+/+ mice. In the elevated zero maze, opposite effects of MA on activity and measures of anxiety were seen in Hdc+/+ mice. In contrast, MA similarly increased the shock-startle response in Hdc−/− and Hdc+/+ mice, compared to saline-treated genotype-matched mice. These results are similar to those in younger mice suggesting that the effects are not age-dependent. Overall, single or repeated MA treatment causes histamine-dependent changes in 12-month-old mice in the open field and elevated zero-maze, but not in the shock-startle response. PMID:21466792

BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine.

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Manning, Elizabeth E; Halberstadt, Adam L; van den Buuse, Maarten

2016-04-01

One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-amphetamine challenge was tested in photocell cages after a 2-week withdrawal period. Methamphetamine-treated wild-type mice, but not brain-derived neurotrophic factor heterozygous mice, showed locomotor sensitization to acute 3mg/kg D-amphetamine. Qualitative analysis of exploration revealed tolerance to D-amphetamine effects on entropy in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice, but not wild-type mice. Chronic methamphetamine exposure induces contrasting profiles of behavioral changes in wild-type and brain-derived neurotrophic factor heterozygous mice, with attenuation of behaviors relevant to psychosis in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice. This suggests that brain-derived neurotrophic factor signalling changes may contribute to development of psychosis in methamphetamine users. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Contingency management for the treatment of methamphetamine use disorders.

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Roll, John M; Petry, Nancy M; Stitzer, Maxine L; Brecht, Mary L; Peirce, Jessica M; McCann, Michael J; Blaine, Jack; MacDonald, Marilyn; DiMaria, Joan; Lucero, Leroy; Kellogg, Scott

2006-11-01

Theory and some preliminary evidence suggest that contingency management may be an effective treatment strategy or adjunct to psychosocial treatment for methamphetamine use disorders. An experimentally rigorous investigation on the topic was provided by a large multisite trial conducted under the auspices of the Clinical Trials Network of the National Institute on Drug Abuse. The authors report data on 113 participants who were diagnosed with methamphetamine abuse or dependence. They were randomly assigned to receive 12 weeks of either treatment as usual or treatment as usual plus contingency management. Urine samples were tested for illicit drugs, and breath samples were tested for alcohol. The reinforcers for drug-negative samples were plastic chips, some of which could be exchanged for prizes. The number of plastic chips drawn increased with each week of negative samples but was reset to one after a missed or positive sample. The participants in both groups remained in treatment for equivalent times, but those receiving contingency management in addition to usual treatment submitted significantly more negative samples, and they were abstinent for a longer period of time (5 versus 3 weeks). These results suggest that contingency management has promise as a component in treatment strategies for methamphetamine use disorder.

Prevalence and nature of cardiovascular disease in methamphetamine-related death: A national study.

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Darke, Shane; Duflou, Johan; Kaye, Sharlene

2017-10-01

Methamphetamine dependence is a major public health problem. This study examined the nature, and extent, of cardiovascular disease amongst cases of methamphetamine-related death in Australia, 2009-2015. Analysis of 894 cases of methamphetamine-related death with full autopsy reports retrieved from the National Coronial Information System. The mean age was 37.9yrs (range 15-69yrs) and 78.5% were male. A quarter (26.3%) of cases had enlarged hearts and left ventricular hypertrophy was diagnosed in 18.9%. Severe coronary artery disease was present in 19.0%, the left coronary artery being the vessel most frequently stenosed (16.6%). Replacement fibrosis (evidence of earlier ischaemic events) in the heart muscle was observed in 19.8% of cases, and cardiomyopathy was diagnosed in 5.5%. Histological evidence of hypertension was observed in 32.7% of cases. With the exception of cardiomyopathy, equally common amongst both sexes, cardiovascular disease was more common amongst males, and those aged >35yrs. Clinically significant levels of cardiovascular disease were also observed amongst cases where the cause of death was not attributed to cardiovascular disease: cardiomegaly (19.3%), left ventricular hypertrophy (14.6%), severe coronary artery disease (9.4%), replacement fibrosis (14.4%), cardiomyopathy (3.3%). Cardiovascular disease was highly prevalent, despite the relatively young age of cases. With methamphetamine use increasing rapidly in major regions, cardiovascular disease and cardiovascular-related death will likely increase amongst methamphetamine users. Copyright © 2017 Elsevier B.V. All rights reserved.

A qualitative study of methamphetamine initiation in Cape Town, South Africa

Science.gov (United States)

Hobkirk, Andréa L.; Watt, Melissa H.; Myers, Bronwyn; Skinner, Donald; Meade, Christina S.

2015-01-01

Background Despite a significant rise in methamphetamine use in low- and middle-income countries, there has been little empirical examination of the factors that contribute to individuals’ initiation of methamphetamine use in these settings. The goal of this study was to qualitatively examine factors associated with methamphetamine initiation in South Africa. Methods In-depth interviews were conducted with 30 active methamphetamine users (13 women and 17 men) in Cape Town, South Africa. Interviews included narrative descriptions of the circumstances surrounding methamphetamine initiation. Interviews were audio recorded, transcribed, and translated. Transcripts were analyzed with document memos, data display matrices, and a constant comparison technique to identify themes. Results On average, participants began regularly using methamphetamine around age 21 and had used for seven years. Four major themes emerged related to the initiation of methamphetamine use. The prevalence of methamphetamine users and distributors made the drug convenient and highly accessible to first time users. Methamphetamine has increased in popularity and is considered “trendy”, which contributes to social pressure from friends, and less often, family members to initiate use. Initiation is further fueled by a lack of opportunities for recreation and employment, which leads to boredom and curiosity about the rumored positive effects of the drug. Young people also turn to methamphetamine use and distribution through gang membership as an attempt to generate income in impoverished communities with limited economic opportunities. Finally, participants described initiating methamphetamine as a means of coping with the cumulative stress and psychological burden provoked by the high rates of violence and crime in areas of Cape Town. Conclusion The findings highlight the complex nature of methamphetamine initiation in low- and middle-income countries like South Africa. There is a need for

A qualitative study of methamphetamine initiation in Cape Town, South Africa.

Science.gov (United States)

Hobkirk, Andréa L; Watt, Melissa H; Myers, Bronwyn; Skinner, Donald; Meade, Christina S

2016-04-01

Despite a significant rise in methamphetamine use in low- and middle-income countries, there has been little empirical examination of the factors that contribute to individuals' initiation of methamphetamine use in these settings. The goal of this study was to qualitatively examine factors associated with methamphetamine initiation in South Africa. In-depth interviews were conducted with 30 active methamphetamine users (13 women and 17 men) in Cape Town, South Africa. Interviews included narrative descriptions of the circumstances surrounding methamphetamine initiation. Interviews were audio recorded, transcribed, and translated. Transcripts were analyzed with document memos, data display matrices, and a constant comparison technique to identify themes. On average, participants began regularly using methamphetamine around age 21 and had used for seven years. Four major themes emerged related to the initiation of methamphetamine use. The prevalence of methamphetamine users and distributors made the drug convenient and highly accessible to first time users. Methamphetamine has increased in popularity and is considered "trendy", which contributes to social pressure from friends, and less often, family members to initiate use. Initiation is further fueled by a lack of opportunities for recreation and employment, which leads to boredom and curiosity about the rumored positive effects of the drug. Young people also turn to methamphetamine use and distribution through gang membership as an attempt to generate income in impoverished communities with limited economic opportunities. Finally, participants described initiating methamphetamine as a means of coping with the cumulative stress and psychological burden provoked by the high rates of violence and crime in areas of Cape Town. The findings highlight the complex nature of methamphetamine initiation in low- and middle-income countries like South Africa. There is a need for community-level interventions to address the

Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

International Nuclear Information System (INIS)

Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

2010-01-01

Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with ( 11 C)d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of ( 11 C)d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

Energy Technology Data Exchange (ETDEWEB)

Volkow, N.D.; Fowler, J.; Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

2010-12-01

Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [{sup 11}C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight {approx}1246 g), liver (23%; weight {approx}1677 g) and intermediate in brain (10%; weight {approx}1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [{sup 11}C]d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

Bee venom suppresses methamphetamine-induced conditioned place preference in mice.

Science.gov (United States)

Kwon, Young Bae; Li, Jing; Kook, Ji Ae; Kim, Tae Wan; Jeong, Young Chan; Son, Ji Seon; Lee, Hyejung; Kim, Kee Won; Lee, Jang Hern

2010-02-01

Although acupuncture is most commonly used for its analgesic effect, it has also been used to treat various drug addictions including cocaine and morphine in humans. This study was designed to investigate the effect of bee venom injection on methamphetamine-induced addictive behaviors including conditioned place preference and hyperlocomotion in mice. Methamphetamine (1 mg/kg) was subcutaneously treated on days 1, 3 and 5 and the acquisition of addictive behaviors was assessed on day 7. After confirming extinction of addictive behaviors on day 17, addictive behaviors reinstated by priming dose of methamphetamine (0.1 mg/kg) was evaluated on day 18. Bee venom (20 microl of 1 mg/ml in saline) was injected to the acupuncture point ST36 on days 1, 3 and 5. Repeated bee venom injections completely blocked development of methamphetamine-induced acquisition and subsequent reinstatement. Single bee venom acupuncture 30 minutes before acquisition and reinstatement test completely inhibited methamphetamine-induced acquisition and reinstatement. Repeated bee venom acupunctures from day 8 to day 12 after methamphetamine-induced acquisition partially but significantly suppressed reinstatement. These findings suggest that bee venom acupuncture has a preventive and therapeutic effect on methamphetamine-induced addiction.

Increased blood 8-hydroxy-2-deoxyguanosine levels in methamphetamine users during early abstinence.

Science.gov (United States)

Huang, Ming-Chyi; Lai, Ying-Ching; Lin, Shih-Ku; Chen, Chun-Hsin

2018-01-01

Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage. This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence. We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement. The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use. Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.

Desorption of a methamphetamine surrogate from wallboard under remediation conditions

Science.gov (United States)

Poppendieck, Dustin; Morrison, Glenn; Corsi, Richard

2015-04-01

Thousands of homes in the United States are found to be contaminated with methamphetamine each year. Buildings used to produce illicit methamphetamine are typically remediated by removing soft furnishings and stained materials, cleaning and sometimes encapsulating surfaces using paint. Methamphetamine that has penetrated into paint films, wood and other permanent materials can be slowly released back into the building air over time, exposing future occupants and re-contaminating furnishings. The objective of this study was to determine the efficacy of two wallboard remediation techniques for homes contaminated with methamphetamine: 1) enhancing desorption by elevating temperature and relative humidity while ventilating the interior space, and 2) painting over affected wallboard to seal the methamphetamine in place. The emission of a methamphetamine surrogate, N-isopropylbenzylamine (NIBA), from pre-dosed wallboard chambers over 20 days at 32 °C and two values of relative humidity were studied. Emission rates from wallboard after 15 days at 32 °C ranged from 35 to 1400 μg h-1 m-2. Less than 22% of the NIBA was removed from the chambers over three weeks. Results indicate that elevating temperatures during remediation and latex painting of impacted wallboard will not significantly reduce freebase methamphetamine emissions from wallboard. Raising the relative humidity from 27% to 49% increased the emission rates by a factor of 1.4. A steady-state model of a typical home using the emission rates from this study and typical residential building parameters and conditions shows that adult inhalation reference doses for methamphetamine will be reached when approximately 1 g of methamphetamine is present in the wallboard of a house.

Need for Methamphetamine Programming in Extension Education

Science.gov (United States)

Beaudreault, Amy R.; Miller, Larry E.

2011-01-01

The study reported sought to identify the prevention education needs involving methamphetamine through survey methodology. The study focused on a random sample of U.S. states and the Extension Directors within each state, resulting in a 70% response rate (n = 134). Findings revealed that 11% reported they had received methamphetamine user…

Treatment of Narcolepsy with Methamphetamine

OpenAIRE

Miller, Merrill M.; Hajdukovic, Roza; Erman, Milton K.

1993-01-01

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 1...

Development and validation of a Thai stressful life events rating scale for patients with a diagnosis of schizophrenic methamphetamine abuse

OpenAIRE

Ek-uma Imkome; JintanaYunibhand; Waraporn Chaiyawat

2017-01-01

This study aimed to psychometrically test a Thai Stressful Life Events Rating Scale (TSLERS). Factor analysis was done on data collected from 313 patients with schizophrenia and methamphetamine abuse in Thailand from April to May, 2015. Results identified the following problems impacting physical and mental health: social relationship and social concerns, money, family life, life security, and career. Evaluation of the psychometric scale properties demonstrated acceptable validity ...

Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

International Nuclear Information System (INIS)

Ke, J.-J.; Chen, H.-I.; Jen, C.J.; Kuo, Y.-M.; Cherng, C.G.; Tsai, Y.-P.N.; Ho, M.-C.; Tsai, C.-W.; Lung Yu

2008-01-01

We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergic damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation

Methamphetamine and amphetamine concentrations in postmortem rabbit tissues.

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Nagata, T; Kimura, K; Hara, K; Kudo, K

1990-11-01

The feasibility of detecting methamphetamine and its major metabolite, amphetamine, in postmortem tissues over a 2-year period was examined. It is important to determine if the abuse and toxic effects of drugs can be proved from evidence found in decayed, submerged, or stained tissue materials. The blood, urine, liver, skeletal muscle, skin and extremity bones from rabbits given methamphetamine intravenously were kept at room temperature, under 4 different conditions: sealed in a test tube, dried in the open air, submerged in tap water and stained on gauze. Methamphetamine was present in all the samples, with slight change in concentration in case of sealed and air dried tissues. Changes varied in bones kept in water. There were considerable decreases in methamphetamine in blood and urine stains. Despite long term storage, drug abuse and/or toxicity could be determined, in all tissues examined.

Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[11C]methamphetamine and ( - )-[11C]methamphetamine in a monkey brain

International Nuclear Information System (INIS)

Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O'Rourke, Maria F.

1995-01-01

Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [ 11 C]H 3 I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/μM. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes

Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

International Nuclear Information System (INIS)

Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael

2005-01-01

These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats

Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

Science.gov (United States)

Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

2012-01-01

Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

The role of hyperthermia and metabolism as mechanisms of tolerance to methamphetamine neurotoxicity.

Science.gov (United States)

Johnson-Davis, Kamisha L; Fleckenstein, Annette E; Wilkins, Diana G

2003-12-15

Pretreatment with multiple methamphetamine injections prior to a high-dose methamphetamine challenge administration can attenuate long-term deficits in striatal and hippocampal serotonin content caused by the stimulant. The present data extend previous findings by demonstrating that rats pretreated with escalating doses methamphetamine did not exhibit dopamine deficits in the striatum, nor serotonin deficits in striatal, frontal cortical, or hippocampal tissues, 7 days after a challenge methamphetamine administration. This protection was not due to attenuation of methamphetamine-induced hyperthermia or altered brain methamphetamine concentrations. These data differ from previous findings thereby highlighting that different mechanisms contribute to the tolerance of the neurotoxic effects.

Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

Science.gov (United States)

Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

2017-07-01

Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Methamphetamine: An Update on Epidemiology, Pharmacology, Clinical Phenomenology, and Treatment Literature

Science.gov (United States)

Courtney, Kelly E.; Ray, Lara A.

2014-01-01

Background Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods Specifically, we first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. Conclusion Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research. PMID:25176528

Quantification of Methamphetamine in Mouse Thighbones Buried in Soil.

Science.gov (United States)

Nakao, Ken-Ichiro; Tatara, Yuki; Kibayashi, Kazuhiko

2017-11-01

Bone samples are used for analysis of drugs in decomposed or skeletonized bodies. Toxicological analyses of buried bones are important for determining the causes and circumstances of death. In this study, methamphetamine and amphetamine concentrations in heart blood, thigh muscles, and thighbones were analyzed using solid-phase extraction with liquid chromatography-tandem mass spectrometry. Methamphetamine concentrations in heart blood, thigh muscle, and thighbone ranged from 0.041 to 0.873 μg/mL, 0.649 to 2.623 μg/g, and 56.543 to 643.371 μg/g, respectively. Thighbone concentrations were significantly higher than those in heart blood or thigh muscles were. Methamphetamine concentrations in buried thighbone (4.010-45.785 μg/g) were significantly lower than those of unburied thighbones were (56.543-643.371 μg/g). Methamphetamine and amphetamine were detected in thighbones buried for 7-180 days. These findings indicate that the methamphetamine concentrations in bone are higher and decrease after burial in soil. © 2017 American Academy of Forensic Sciences.

Structural factors associated with methamphetamine smoking among female sex workers in Tijuana, Mexico.

Science.gov (United States)

Conners, Erin E; Gaines, Tommi L; Strathdee, Steffanie A; Magis-Rodriguez, Carlos; Brouwer, Kimberly C

2018-04-01

Smoking methamphetamine is associated with increased risk of HIV among female sex workers (FSW). The structural context of substance use is an important shaper of individual behaviour; however, structural determinants of methamphetamine use among FSWs are largely unknown. We identified individual, structural and neighbourhood factors associated with smoking methamphetamine among FSWs in the border city of Tijuana, Baja California, Mexico. A prospective cohort of 301 FSWs sampled from indoor and outdoor sex work venues throughout Tijuana participated in quantitative surveys on behaviours and mapping of home and work neighbourhoods across three visits. Multinomial logistic regression using generalised estimating equations identified individual, structural and neighbourhood variables associated with smoking methamphetamine. Methamphetamine use, particularly smoking, was highly prevalent among FSWs. Over half (61%) of FSWs had ever used methamphetamine in their lifetime and at baseline, 38% currently smoked methamphetamine. Smoking methamphetamine daily was associated with living in the red light district [adjusted odds ratio (AOR) = 2.72, 95% confidence interval (CI) = 1.23-6.02] and with perceived homelessness, but only among women in a good financial situation (AOR = 4.08, 95% CI = 1.58-10.50). Smoking methamphetamine less than daily was associated with older age (AOR = 1.06, 95% CI = 1.02-1.10). Our findings point to the important dynamic between the residential environment and more severe methamphetamine use. FSWs may prioritise the purchase of methamphetamine over stable housing if they have the financial means. Given the high prevalence of smoking methamphetamine among FSWs in Tijuana, drug treatment options, especially for women living in the red light district, are needed. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Ice and the outback: Patterns and prevalence of methamphetamine use in rural Australia.

Science.gov (United States)

Roche, Ann; McEntee, Alice

2017-08-01

This study investigated whether lifetime and recent methamphetamine use (including crystal methamphetamine) differed among city, regional and rural residents and whether particular subpopulations were more at-risk. Secondary analyses of the last three National Drug Strategy Household Surveys and corresponding Alcohol and Other Drug Treatment Services National Minimum Data Sets (AODTS NMDS). Australian general population. Australians who completed the 2007 (n = 22 519), 2010 (n = 25 786) and 2013 (n = 23 512) NDSHS (aged 14 + ); and treatment episodes where the principal drug of concern was recorded in the 2006/2007 (n = 139 808), 2009/2010 (n = 139 608) and 2012/2013 (n = 154 489) AODTS NMDS. To determine whether rural Australians were more likely to use methamphetamine than non-rural counterparts. Lifetime and recent methamphetamine and recent crystal methamphetamine use were significantly higher among rural than other Australians. Significantly more rural men and employed rural Australians used methamphetamine than their city, regional or Australian counterparts. Rural Australians aged 18-24 and 25-29 years were significantly more likely to have used methamphetamine in their lifetime than city or Australian residents. Rural Australians aged 18-24 years were significantly more likely to have recently used crystal methamphetamine. Interventions tailored to address the specific and unique circumstances of rural settings are required to reduce and prevent methamphetamine use, particularly crystal methamphetamine. Scope exists to focus prevention efforts on rural workplaces and primary care settings. Greater understanding of the higher prevalence of methamphetamine use in rural areas is required, plus implementation of comprehensive strategies and optimised treatment utilisation. © 2016 National Rural Health Alliance Inc.

Partial MHC/neuroantigen peptide constructs: a potential neuroimmune-based treatment for methamphetamine addiction.

Directory of Open Access Journals (Sweden)

Jennifer M Loftis

Full Text Available Relapse rates following current methamphetamine abuse treatments are very high (∼40-60%, and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-A(b/mMOG-35-55, in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.. Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2 levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments.

Dose-response relationships between exercise intensity, cravings, and inhibitory control in methamphetamine dependence: An ERPs study.

Science.gov (United States)

Wang, Dongshi; Zhou, Chenglin; Zhao, Min; Wu, Xueping; Chang, Yu-Kai

2016-04-01

The present study integrated behavioral and neuroelectric approaches for determining the dose-response relationships between exercise intensity and methamphetamine (MA) craving and between exercise intensity and inhibitory control in individuals with MA dependence. Ninety-two individuals with MA dependence were randomly assigned to an exercise group (light, moderate, or vigorous intensity) or to a reading control group. The participants then completed a craving self-report at four time points: before exercise, during exercise, immediately after exercise, and 50 min after exercise. Event-related potentials were also recorded while the participants completed a standard Go/NoGo task and an MA-related Go/NoGo task approximately 20 min after exercise cessation. The reduction in self-reported MA craving scores of the moderate and vigorous intensity groups was greater than that of the light intensity and control groups during acute exercise as well as immediately and 50 min following exercise termination. Additionally, an inverted-U-shaped relationship between exercise intensity and inhibitory control was generally observed for the behavioral and neuroelectric indices, with the moderate intensity group exhibiting shorter Go reaction times, increased NoGo accuracy, and larger NoGo-N2 amplitudes. Acute exercise may provide benefits for MA-associated craving and inhibitory control in MA-dependent individuals, as revealed by behavioral and neuroelectric measures. Moderate-intensity exercise may be associated with more positive effects, providing preliminary evidence for the establishment of an exercise prescription regarding intensity for MA dependence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Breast abscess after intravenous methamphetamine injection into the breast.

Science.gov (United States)

Kistler, Amanda; Ajkay, Nicolas

2018-05-01

Intravenous drug use is a problem plaguing our society. We present a case of a young female who injected methamphetamine into her mammary vein, resulting in the formation of a breast abscess. This case demonstrates a rare but dangerous complication of intravenous drug use and a possible differential diagnosis in a patient presenting with a breast abscess. © 2017 Wiley Periodicals, Inc.

The Effectiveness of Matrix Treatment to Relapse prevention and Increase Self-Efficacy in People Withdrawing Methamphetamine

Directory of Open Access Journals (Sweden)

Siamak Ghasemnezhad

2016-08-01

Full Text Available Given the prevalence of narcotic substances and their effect on mental health of society people, it is important to pay attention the matter and adopt an approach for its treatment. The research objective is to examine the effectiveness of matrix treatment on prevent relapsing and increase self-efficacy in people withdrawing methamphetamine. In a quasi-experimental design, methamphetamine users who referred to addiction treatment centers on west of Gilanin 2015 and were eligible for involving criteria completed theself efficacy questionnaire. Then among those who got low scores on this questionnaire, there were randomly selected 30 patients that were divided into experimental and control groups (15 patients for each group. The experimental group was treated for 18 weeks and two sessions per week (36 sessions using matrix therapeutic model. The control group remained on waiting list. Both groups completed self-efficacy questionnaire at baseline, end and 90 days later (follow-up stage with urine test. The control group remained on waiting list and there were assigned only common drug treatment in the withdrawal centers. The research data was analyzed using covariance analysis and SPSS22 software. The results showed efficiency of matrix treatment method in preventing relapse and increasing self-efficacy for people withdrawal methamphetamine, which this difference was statistically significant (p<0.5. Matrix-based treatmentis effective for relapse prevention and increasing self-efficacy for people withdrawal methamphetamine.

Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[{sup 11}C]methamphetamine and ( - )-[{sup 11}C]methamphetamine in a monkey brain

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Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O' Rourke, Maria F

1995-04-01

Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [{sup 11}C]H{sub 3}I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/{mu}M. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes.

Identification of Treatment Targets in a Genetic Mouse Model of Voluntary Methamphetamine Drinking.

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Phillips, T J; Mootz, J R K; Reed, C

2016-01-01

Methamphetamine has powerful stimulant and euphoric effects that are experienced as rewarding and encourage use. Methamphetamine addiction is associated with debilitating illnesses, destroyed relationships, child neglect, violence, and crime; but after many years of research, broadly effective medications have not been identified. Individual differences that may impact not only risk for developing a methamphetamine use disorder but also affect treatment response have not been fully considered. Human studies have identified candidate genes that may be relevant, but lack of control over drug history, the common use or coabuse of multiple addictive drugs, and restrictions on the types of data that can be collected in humans are barriers to progress. To overcome some of these issues, a genetic animal model comprised of lines of mice selectively bred for high and low voluntary methamphetamine intake was developed to identify risk and protective alleles for methamphetamine consumption, and identify therapeutic targets. The mu opioid receptor gene was supported as a target for genes within a top-ranked transcription factor network associated with level of methamphetamine intake. In addition, mice that consume high levels of methamphetamine were found to possess a nonfunctional form of the trace amine-associated receptor 1 (TAAR1). The Taar1 gene is within a mouse chromosome 10 quantitative trait locus for methamphetamine consumption, and TAAR1 function determines sensitivity to aversive effects of methamphetamine that may curb intake. The genes, gene interaction partners, and protein products identified in this genetic mouse model represent treatment target candidates for methamphetamine addiction. © 2016 Elsevier Inc. All rights reserved.

Frequency of osteoporosis in 46 men with methamphetamine abuse hospitalized in a National Hospital.

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Kim, Eun Young; Kwon, Do Hoon; Lee, Byung Dae; Kim, Yang Tae; Ahn, Young Bok; Yoon, Kuee Young; Sa, Sok Jin; Cho, Woong; Cho, Sung Nam

2009-07-01

Methamphetamine, a derivative of amphetamine, has been well known to cause mental problems in humans; however, its physical effects are little known. Despite relevant information on the effect of methamphetamine abuse on bone quality being available, data regarding the frequency of osteoporosis in methamphetamine abusers are limited. We selected 46 hospitalized male methamphetamine abusers and 188 reference male controls in whom any conditions affecting bone metabolism were ruled out. Bone mineral density (BMD) in the lumbar spine was measured by dual energy X-ray absorptiometry (DXA). We compared the BMD between methamphetamine abusers and controls and evaluated the frequency of osteoporosis in both groups. The mean BMD value was lower in methamphetamine abusers (mean+/-SD, 0.71+/-0.07 g/cm(2)) than in the controls (mean+/-SD, 0.98+/-0.14 g/cm(2)). The frequency of osteoporosis was 22% according to WHO diagnostic guidelines, and osteopenia at the lumbar spine was 76%. The correlation between the extent of methamphetamine abuse and BMD was very clear. There was considerable loss of bone mineral in a high percentage of methamphetamine abusers. Our study is the first clinical study to determine the frequency of osteoporosis in male methamphetamine abusers.

Methamphetamine protects against MPTP neurotoxicity in C57BL mice.

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Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Budai, G

1994-01-14

Methamphetamine (5 mg/kg) administered 30 min prior to each injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (3 x 30 mg/kg, at 24 h intervals) prevents the reduction of striatal levels of dopamine and its metabolites in C57BL mice. Methamphetamine and amphetamine inhibit the uptake of 1-methyl-4-phenylpyridinium (MPP+) by striatal synaptosomes of rats. A 30-min post-treatment with methamphetamine or amphetamine also prevents the MPTP-induced dopamine depletion, suggesting that their protective effect is related to the blockade of MPP+ uptake into dopaminergic neurons. Since amphetamine and methamphetamine are themselves neurotoxins at higher doses, this work demonstrated the protection against the actions of one neurotoxin by the administration of another.

Methamphetamine fails to alter the noradrenergic integrity of the heart.

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Ruffoli, Riccardo; Soldani, Paola; Pasquali, Livia; Ruggieri, Stefano; Paparelli, Antonio; Fornai, Francesco

2008-10-01

The chronic use of methamphetamine leads to cardiomyopathy and a nigrostriatal dopamine deficiency that partly mimics what occurs in Parkinson's disease. This study examines the cardiac effects occurring after chronic administration of methamphetamine and parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Despite the similarities concerning the nigrostriatal dopamine denervation, methamphetamine failed to produce chronic norepinephrine depletion in the heart, thus contrasting with what occurs in Parkinson's disease or after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These data suggest that the chronic cardiovascular effects induced by methamphetamine rely on biochemical changes which differ from those activated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or during the course of Parkinson's disease.

PKCδ-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity.

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Dang, Duy-Khanh; Shin, Eun-Joo; Kim, Dae-Joong; Tran, Hai-Quyen; Jeong, Ji Hoon; Jang, Choon-Gon; Ottersen, Ole Petter; Nah, Seung-Yeol; Hong, Jau-Shyong; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2018-02-01

Protein kinase C (PKC) has been recognized to activate NADPH oxidase (PHOX). However, the interaction between PKC and PHOX in vivo remains elusive. Treatment with methamphetamine (MA) resulted in a selective increase in PKCδ expression out of PKC isoforms. PKCδ co-immunoprecipitated with p47phox, and facilitated phosphorylation and membrane translocation of p47phox. MA-induced increases in PHOX activity and reactive oxygen species were attenuated by knockout of p47phox or PKCδ. In addition, MA-induced impairments in the Nrf-2-related glutathione synthetic system were also mitigated by knockout of p47phox or PKCδ. Glutathione-immunoreactivity was co-localized in Iba-1-labeled microglial cells and in NeuN-labeled neurons, but not in GFAP-labeled astrocytes, reflecting the necessity for self-protection against oxidative stress by mainly microglia. Buthionine-sulfoximine, an inhibitor of glutathione biosynthesis, potentiated microglial activation and pro-apoptotic changes, leading to dopaminergic losses. These neurotoxic processes were attenuated by rottlerin, a pharmacological inhibitor of PKCδ, genetic inhibitions of PKCδ [i.e., PKCδ knockout mice (KO) and PKCδ antisense oligonucleotide (ASO)], or genetic inhibition of p47phox (i.e., p47phox KO or p47phox ASO). Rottlerin did not exhibit any additive effects against the protective activity offered by genetic inhibition of p47phox. Therefore, we suggest that PKCδ is a critical regulator for p47phox activation induced by MA, and that Nrf-2-dependent GSH induction via inhibition of PKCδ or p47phox, is important for dopaminergic protection against MA insult. Copyright © 2017 Elsevier Inc. All rights reserved.

21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

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2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine (also...

[Comparative study on effects between electroacupuncture and auricular acupuncture for methamphetamine withdrawal syndrome].

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Liang, Yan; Xu, Bo; Zhang, Xue-Chun; Zong, Lei; Chen, Yue-Lai

2014-03-01

To observe the efficacy difference of electroacupuncture and auricular acupuncture in the treatment of methamphetamine withdrawal syndrome. Ninety male patients of methamphetamine addiction were randomized into an electroacupuncture group, an auricular acupuncture group and a control group, 30 cases in each one. In the electroacupuncture group, Neiguan (PC 6), Shenmen (HT 7), Zusanli (ST 36), Sanyinjiao (SP 6), Jiaji (EX-B 2) at T5 and L2 were selected bilaterally. In the auricular acupuncture group, jiaogan (AH(6a)), shenmen (TF4), fei (CO14) and gan (CO12) were selected unilaterally. The treatment was given 3 times a week, totally 12 treatments were required. In the control group, no any intervention was applied. Separately, before treatment and after 1, 2, 3 and 4 weeks treatment, the scores of methamphetamine withdrawal syndrome, Hamilton anxiety scale and Hamilton depression scale were observed in each group. The total score of methamphetamine withdrawal syndrome, anxiety score and depression score were obviously reduced in 2, 3 and 4 weeks of treatment as compared with those before treatment in the electroacupuncture group and the auricular acupuncture group (all P electroacupuncture group and auricular acupuncture group were lower significantly than those in the control group (all P electroacupuncture group was lower significantly than that in the auricular acupuncture group in the 4th week of treatment (3.69 +/- 2.446 vs 5.73 +/- 3.169, P Electroacupuncture at the body points and auricular acupuncture play the therapeutic role in the treatment of methamphetamine withdrawal syndrome, anxiety and depression. The longer time the treatment is with electroacupuncture at the body points, the more obvious the efficacy will be on the above symptoms.

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

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Amanda L Persons

Full Text Available The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1, two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

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Persons, Amanda L; Bradaric, Brinda D; Dodiya, Hemraj B; Ohene-Nyako, Michael; Forsyth, Christopher B; Keshavarzian, Ali; Shaikh, Maliha; Napier, T Celeste

2018-01-01

The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

A comparison of economic demand and conditioned-cued reinstatement of methamphetamine- or food-seeking in rats

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Galuska, Chad M.; Banna, Kelly M.; Willse, Lena Vaughn; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

2011-01-01

The present study examined whether continued access to methamphetamine or food reinforcement changed economic demand for both. The relationship between demand elasticity and cue-induced reinstatement was also determined. Male Long-Evans rats lever-pressed under increasing fixed-ratio requirements for either food pellets or methamphetamine (20 μg/50 μl infusion). For two groups, demand curves were obtained before and after continued access (12 days, 2-hr sessions) to the reinforcer under a fixed-ratio 3 schedule. A third group was given continued access to methamphetamine between determinations of food demand and a fourth group abstained from methamphetamine between determinations. All groups underwent extinction sessions, followed by a cue-induced reinstatement test. Although food demand was less elastic than methamphetamine demand, continued access to methamphetamine shifted the methamphetamine demand curve upward and the food demand curve downward. In some rats, methamphetamine demand also became less elastic. Continued access to food had no effect on food demand. Reinstatement was higher after continued access to methamphetamine relative to food. For methamphetamine, elasticity and reinstatement measures were correlated. We conclude that continued access to methamphetamine – but not food – alters demand in ways suggestive of methamphetamine accruing reinforcing strength. Demand elasticity and reinstatement measures appear to be related indices of drug-seeking. PMID:21597363

Methamphetamine Use among Iranian Youth: A Population-based Knowledge, Attitude, and Practice study.

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Sharifi, Hamid; Shokoohi, Mostafa; Ahmad RafieiRad, Ali; Sargolzaie Moghadam, Maryam; Haghdoost, Ali-Akbar; Mirzazadeh, Ali; Karamouzian, Mohammad

2017-07-29

Despite the increasing prevalence of methamphetamine use among the young population in Iran, the body of literature on their methamphetamine use remains slim. This study was designed to investigate the knowledge, attitude, and practices of Iranian youth about methamphetamine to help inform harm reduction policies catered towards young men and women. In a cross-sectional study using multistage sampling in 13 provinces, 4868 participants aged 15-29 years old were recruited. Knowledge, attitude and practices of youth about methamphetamine were assessed through a pilot-tested interviewer-administered questionnaire. Descriptive statistics were presented and potential associations were assessed using Chi-square test and independent samples t-test. Mean age ±SD of the participants was 21.8 ± 5.6 years, and 49.5% were women. Overall, 21.7% and 37.7% of the participants had high knowledge scores and positive attitudes, respectively. Among the 19-29 years old participants, ever methamphetamine use and injection was estimated at 5.74% (95% CI: 4.21, 7.90) and 1.8% (95% CI: 1.13, 2.83), respectively. Most (44.3%) had started methamphetamine use for fun and media (69.1%) was reported as their main source of information on methamphetamine use. Methamphetamine use is a concerning health problem among Iranian youth. Comprehensive multi-sectoral downstream and upstream interventions that involve educational settings, as well as media, are urgently needed to help reduce the burden of methamphetamine use among Iranian youth.

Methamphetamine functions as a positive and negative drug feature in a Pavlovian appetitive discrimination task.

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Reichel, Carmela M; Wilkinson, Jamie L; Bevins, Rick A

2007-12-01

This research determined the ability of methamphetamine to serve as a positive or negative feature, and assessed the ability of bupropion, cocaine, and naloxone to substitute for the methamphetamine features. Rats received methamphetamine (0.5 mg/kg, intraperitoneally) or saline 15 min before a conditioning session. For the feature positive (FP) group, offset of 15-s cue lights was followed by access to sucrose on methamphetamine sessions; sucrose was withheld during saline sessions. For the feature negative (FN) group, the light offset was followed by sucrose on saline sessions; sucrose was withheld during methamphetamine sessions. During acquisition, the FP group had higher responding on methamphetamine sessions than on saline sessions. For the FN group, responding was higher on saline sessions than on methamphetamine sessions. Conditioned responding was sensitive to methamphetamine dose. For the FP group, bupropion and cocaine fully and partially substituted for methamphetamine, respectively. In contrast, both drugs fully substituted for methamphetamine in the FN group. Naloxone did not substitute in either set of rats. FP-trained rats were more sensitive to the locomotor stimulating effects of the test drugs than FN-trained rats. This research demonstrates that the pharmacological effects of methamphetamine function as a FP or FN in this Pavlovian discrimination task and that training history can affect conditioned responding and locomotor effects evoked by a drug.

Review: Methamphetamine use by pregnant women: Impact on the ...

African Journals Online (AJOL)

According to the United Nations Office on Drugs and Crime (UNODC)'s 2011 World Drug Report, amphetamine-type stimulants (ATS) are the second most widely used illicit drug group. This drug group comprises methamphetamine, amphetamine and ecstasy. Methamphetamine is the most widely manufactured drug in this ...

Differential effects of the ascorbyl and tocopheryl derivative on the methamphetamine-induced toxic behavior and toxicity

International Nuclear Information System (INIS)

Ito, Shinobu; Mori, Tomohisa; Kanazawa, Hideko; Sawaguchi, Toshiko

2007-01-01

A previous study showed that high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. Furthermore, the combination of methamphetamine and morphine increased lethality in mice. We recently surmised that the rise in SIB and mortality induced by methamphetamine and/or morphine may be related to oxidative stress. The present study was designed to determine whether an antioxidant could inhibit SIB or mortality directly induced by methamphetamine and/or morphine. The SIB induced by 20 mg/kg of methamphetamine was abolished by the administration of Na L-ascorbyl-2-phosphate (APS: 300 mg/kg), but not Na DL-α-tocopheryl phosphate (TPNa: 200 mg/kg). In contrast, APS (300 mg/kg) and TPNa (200 mg/kg) each significantly attenuated the lethality induced by methamphetamine and morphine. The present study showed that the signal intensity of superoxide adduct was increased by 20 mg/kg of methamphetamine in the heart and lungs, and methamphetamine plus morphine tended to increase superoxide adduct in all of the tissues measured by ESR spin trap methods. Adduct signal induced in brain by methamphetamine administration increased in significance, but in mouse administrated methamphetamine plus morphine. There are differential effects of administration of methamphetamine and coadministration of methamphetamine plus morphine on adduct signal. These results suggest that APS and TPNa are effective for reducing methamphetamine-induced toxicity and/or toxicological behavior. While APS and TPNa each affected methamphetamine- and/or morphine-induced toxicology and/or toxicological behavior, indicating that both drugs have antioxidative effects, their effects differed

Delayed emergence of methamphetamine’s enhanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence

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Vaupel, DB; Schindler, CW; Chefer, S; Belcher, AM; Ahmet, I; Scheidweiler, KB; Huestis, MA; Stein, EA

2015-01-01

Background Methamphetamine abuse is linked with brain abnormalities, but its peripheral effects constitute an integral aspect of long-term methamphetamine use. Methods Eight male rhesus monkeys with long histories of intravenous methamphetamine self-administration were evaluated 1 day, and 1, 4, 12, 26, and 52 weeks after their last methamphetamine self-administration session. On test days, isoflurane-anesthetized animals received a 0.35 mg/kg IV methamphetamine challenge. A control group consisted of 10 age and gender matched drug naïve monkeys. Cardiovascular responses to methamphetamine were followed for 2.5 h. Echocardiograms were acquired at 3 and 12 months of abstinence and in the control animals. Results No pre-methamphetamine baseline differences existed among 7 physiological measures across all conditions and controls. As expected, methamphetamine increased heart rate and blood pressure in controls. However, immediately following the self-administration period, the blood pressure response to methamphetamine challenge was reduced when compared to control monkeys. The peak and 150-min average heart rate increases, as well as peak blood pressure increases following methamphetamine were significantly elevated between weeks 12 to 26 of abstinence. These data indicate the development of tolerance followed by sensitization to methamphetamine cardiovascular effects. Echocardiography demonstrated decreased left ventricular ejection fraction and cardiac output at 3 months of abstinence. Importantly, both cardiovascular sensitization and cardiotoxicity appeared to be reversible as they returned toward control group levels after 1 year of abstinence. Conclusions Enhanced cardiovascular effects may occur after prolonged abstinence in addicts relapsing to methamphetamine and may underlie clinically reported acute cardiotoxic events. PMID:26775284

Effect of 7-nitroindazole on body temperature and methamphetamine-induced dopamine toxicity.

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Callahan, B T; Ricaurte, G A

1998-08-24

The present study was undertaken to examine the role of temperature on the ability of 7-nitroindazole (7-NI) to prevent methamphetamine-induced dopamine (DA) neurotoxicity. Male Swiss-Webster mice received methamphetamine alone or in combination with 7-NI at either room temperature (20+/-1 degrees C) or at 28+/-1 degrees C. At 20+/-1 degrees C, 7-NI produced hypothermic effects and afforded total protection against methamphetamine-induced DA depletions in the striatum. At 28+/-1 degrees C, 7-NI produced minimal effects on body temperature and failed to prevent methamphetamine-induced DA reductions. These findings indicate that the neuroprotection afforded by 7-NI is likely related to its ability to produce hypothermia because agents that produce hypothermia and/or prevent hyperthermia are known to attenuate methamphetamine-induced neurotoxicity.

Buspirone maintenance does not alter the reinforcing, subjective, and cardiovascular effects of intranasal methamphetamine.

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Reynolds, Anna R; Strickland, Justin C; Stoops, William W; Lile, Joshua A; Rush, Craig R

2017-12-01

Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. Eight research participants (1 female) reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30mg) were assessed after at least 6days of buspirone (0 and 45mg/day) maintenance. Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

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Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

2012-01-01

Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

The preparation of immunochromatographic stripe of methamphetamine

International Nuclear Information System (INIS)

Jiang Jing; Liu Yibing; Zhou Ling; Guo Weizheng

2004-01-01

A gold immunochromatographic assay (GICA) is developed for methamphetamine in urine. Colloidal gold is obtained by reducing the gold chloride with sodium citrate, and labeled methamphetamine monoclonal antibody. The drug or metabolite competes with the immobilized drug conjugate in the test area for the limited colloidal gold-labeled antibody complex in which the stripe is made to screen the drug abuser. This method has sensitivity of 1000 μg/L, and without cross-reaction with some drugs

School-Related Factors Affecting High School Seniors' Methamphetamine Use

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Stanley, Jarrod M.; Lo, Celia C.

2009-01-01

Data from the 2005 Monitoring the Future survey were used to examine relationships between school-related factors and high school seniors' lifetime methamphetamine use. The study applied logistic regression techniques to evaluate effects of social bonding variables and social learning variables on likelihood of lifetime methamphetamine use. The…

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

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Sonsalla, P K; Nicklas, W J; Heikkila, R E

1989-01-20

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

The Consumption of New Psychoactive Substances and Methamphetamine.

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de Matos, Elena Gomes; Hannemann, Tessa-Virginia; Atzendorf, Josefine; Kraus, Ludwig; Piontek, Daniela

2018-01-26

The abuse of new psychoactive substances (NPS) and methamphetamine has severe adverse effects. Here we provide the first report of regional patterns in NPS and methamphetamine consumption in Germany, on the basis of epidemiologic data from six federal states (Bavaria, Hamburg, Hesse, North Rhine-Westphalia, Saxony, and Thuringia). Data were derived from the 2015 Epidemiological Survey of Substance Abuse (Epidemiologischer Suchtsurvey) and supplemented with additional cases from the federal states that were studied. The numbers of persons included in the representative samples of persons aged 18 to 64 in each state were 1916 (Bavaria), 1125 (Hamburg), 1151 (Hesse), 2008 (North Rhine-Westphalia), 1897 (Saxony), and 1543 (Thuringia). Potential risk factors for the lifetime prevalence of consumption were studied by logistic regression. The lifetime prevalence of methamphetamine consumption in the individual states ranged from 0.3% (North Rhine-Westphalia) to 2.0% (Saxony). Thuringia and Saxony displayed values that were significantly higher than average. For NPS, the figures ranged from 2.2% (Bavaria) to 3.9% (Hamburg), but multivariate analysis revealed no statistically significant differences between the states. Higher age and higher educational level were associated with lower consumption of NPS and methamphetamine, while smoking and cannabis use were each associated with higher consumption. NPS consumption is equally widespread in all of the federal states studied. Methamphetamine is rarely consumed; its consumption appears to be higher in Saxony and Thuringia. The risk factor analysis reported here should be interpreted cautiously in view of the low case numbers with respect to consumption.

Dopamine D(3) receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: role of hyperthermia.

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Baladi, Michelle G; Newman, Amy H; Nielsen, Shannon M; Hanson, Glen R; Fleckenstein, Annette E

2014-06-05

Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. Copyright © 2014 Elsevier B.V. All rights reserved.

Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia

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Baladi, Michelle G.; Newman, Amy H.; Nielsen, Shannon M.; Hanson, Glen R.; Fleckenstein, Annette E.

2014-01-01

Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. PMID:24685638

Chronic Methamphetamine Abuse and Corticostriatal Deficits Revealed by Neuroimaging

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London, Edythe D.; Kohno, Milky; Morales, Angelica; Ballard, Michael E.

2014-01-01

Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets. PMID:25451127

An Exploration of the Relationship between the Use of Methamphetamine and Prescription Drugs

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Lamonica, Aukje K.; Boeri, Miriam

2012-01-01

This study examines patterns of use of prescription drugs and methamphetamine. We drew our sample from a study about 130 active and inactive methamphetamine users and focused on 16 participants with a recent history of methamphetamine and prescription drug use. We collected in-depth interviews to explore relationships in use trajectory patterns.…

A comparison of economic demand and conditioned-cued reinstatement of methamphetamine-seeking or food-seeking in rats.

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Galuska, Chad M; Banna, Kelly M; Willse, Lena Vaughn; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E

2011-08-01

This study examined whether continued access to methamphetamine or food reinforcement changed economic demand for both. The relationship between demand elasticity and cue-induced reinstatement was also determined. Male Long-Evans rats were lever pressed under increasing fixed-ratio requirements for either food pellets or methamphetamine (20 μg/50 μl infusion). For two groups, demand curves were obtained before and after continued access (12 days, 2-h sessions) to the reinforcer under a fixed-ratio 3 schedule. A third group was given continued access to methamphetamine between determinations of food demand and a fourth group abstained from methamphetamine between determinations. All groups underwent extinction sessions, followed by a cue-induced reinstatement test. Although food demand was less elastic than methamphetamine demand, continued access to methamphetamine shifted the methamphetamine demand curve upward and the food demand curve downward. In some rats, methamphetamine demand also became less elastic. Continued access to food had no effect on food demand. Reinstatement was higher after continued access to methamphetamine relative to food. For methamphetamine, elasticity and reinstatement measures were correlated. Continued access to methamphetamine, but not food, alters demand in ways suggestive of methamphetamine accruing reinforcing strength. Demand elasticity thus provides a useful measure of abuse liability that may predict future relapse to renewed drug-seeking and drug use.

Working Memory Deficits Affect Risky Decision-Making in Methamphetamine Users with Attention-Deficit/Hyperactivity Disorder

OpenAIRE

Duarte, Nichole A.; Woods, Steven Paul; Rooney, Alexandra; Atkinson, J. Hampton; Grant, Igor

2012-01-01

Methamphetamine (MA) use and Attention-Deficit/Hyperactivity Disorder (ADHD) commonly co-occur and are independently associated with dysregulation of frontostriatal loops and risky decision-making; however, whether their comorbidity exacerbates risky decision-making is not known. This study evaluated 23 participants with histories of MA dependence and ADHD (MA+ADHD+), 25 subjects with MA dependence alone (MA+ADHD−), and 22 healthy adults (MA−ADHD−), who completed the Iowa Gambling Task (IGT) ...

Methamphetamine-induced dopaminergic toxicity prevented owing to the neuroprotective effects of salicylic acid.

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Thrash-Williams, Bessy; Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

2016-06-01

Methamphetamine (Schedule-II drug, U.S. Drug Enforcement Administration) is one of the most abused illicit drug following cocaine, marijuana, and heroin in the USA. There are numerous health impairments and substantial economic burden caused by methamphetamine abuse. Salicylic acid, potent anti-inflammatory drug and a known neuroprotectant has shown to protect against toxicity-induced by other dopaminergic neurotoxins. Hence, in this study we investigated the neuroprotective effects of salicylic acid against methamphetamine-induced toxicity in mice. The current study investigated the effects of sodium salicylate and/or methamphetamine on oxidative stress, monoamine oxidase, mitochondrial complex I & IV activities using spectrophotometric and fluorimetric methods. Behavioral analysis evaluated the effect on movement disorders-induced by methamphetamine. Monoaminergic neurotransmitter levels were evaluated using high pressure liquid chromatography-electrochemical detection. Methamphetamine caused significant generation of reactive oxygen species and decreased complex-I activity leading to dopamine depletion. Striatal dopamine depletion led to significant behavioral changes associated with movement disorders. Sodium salicylate (50 & 100mg/kg) significantly scavenged reactive oxygen species, blocked mitochondrial dysfunction and exhibited neuroprotection against methamphetamine-induced neurotoxicity. In addition, sodium salicylate significantly blocked methamphetamine-induced behavioral changes related to movement abnormalities. One of the leading causative theories in nigral degeneration associated with movement disorders such as Parkinson's disease is exposure to stimulants, drugs of abuse, insecticide and pesticides. These neurotoxic substances can induce dopaminergic neuronal insult by oxidative stress, apoptosis, mitochondrial dysfunction and inflammation. Salicylic acid due to its antioxidant and anti-inflammatory effects could provide neuroprotection against the

Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits and Obsessive-Compulsive Behavior in Rats

Directory of Open Access Journals (Sweden)

Samira Hajheidari

2017-02-01

Full Text Available Objective: This study was designed to examine the effect of environmental enrichment during methamphetamine (METH dependency and withdrawal on methamphetamine-induced spatial learning and memory deficits and obsessive-compulsive behavior.Method: Adult male Wistar rats (200 ± 10 g chronically received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals for 14 days. Rats reared in standard (SE or enriched environment (EE during the development of dependence on METH and withdrawal. Then, they were tested for spatial learning and memory (the water maze, and obsessive-compulsive behavior as grooming behavior in METH-withdrawn rats.Results: The results revealed that the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on the water maze and displayed significantly increased proximity to the platform compared to their control groups. METH withdrawn rats reared in EE displayed less grooming behavior than METH/SE group.Conclusion: Our findings revealed EE ameliorates METH-induced spatial memory deficits and obsessive-compulsive behavior in rats.

Acupuncture suppresses intravenous methamphetamine self-administration through GABA receptor's mediation.

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Choi, Yi Jeong; Kim, Nam Jun; Zhao, Rong Jie; Kim, Da Hye; Yang, Chae Ha; Kim, Hee Young; Gwak, Young S; Jang, Eun Young; Kim, Jae Su; Lee, Yun Kyu; Lee, Hyun Jong; Lee, Sang Nam; Lim, Sung Chul; Lee, Bong Hyo

2018-01-01

Methamphetamine is one of the widely abused drugs. In spite of a number of studies, there is still little successful therapy to suppress the methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects of psychostimulant. Based on, the present study investigated if acupuncture could suppress intravenous methamphetamine self-administration behavior. In addition, a possible neuronal mechanism was investigated. Male Sprague-Dawley rats weighing 270-300g were trained to intake food pellet. After catheter implantation, animal was trained to self-administer methamphetamine (0.05mg/kg) intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks. After training, rats who established baseline (infusion variation less than 20% of the mean for 3 consecutive days) received acupuncture treatment on the next day. Acupuncture was performed at each acupoint manually. In the second experiment, the selective antagonists of GABA A or GABA B receptor were given before acupuncture to investigate the possible neuronal involvement of GABA receptor pathway in the acupuncture effects. C-Fos expression was examined in the nucleus accumbens to support behavioral data. Acupuncture at HT7, but not at control acupoint LI5, reduced the self-administration behavior significantly. Also, the effects of acupuncture were blocked by the GABA receptor antagonists. C-Fos expression was shown to be parallel with the behavioral data. Results of this study have shown that acupuncture at HT7 suppressed methamphetamine self-administration through GABA receptor system, suggesting that acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Intravenous heroin use in Haiphong, Vietnam: Need for comprehensive care including methamphetamine use-related interventions.

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Michel, Laurent; Des Jarlais, Don C; Duong Thi, Huong; Khuat Thi Hai, Oanh; Pham Minh, Khuê; Peries, Marianne; Vallo, Roselyne; Nham Thi Tuyet, Thanh; Hoang Thi, Giang; Le Sao, Mai; Feelemyer, Jonathan; Vu Hai, Vinh; Moles, Jean-Pierre; Laureillard, Didier; Nagot, Nicolas

2017-10-01

The aim of this study was to describe patterns among people who inject drugs (PWID), risk-related behaviours and access to methadone treatment, in order to design a large-scale intervention aiming to end the HIV epidemic in Haiphong, Vietnam. A respondent-driven sampling (RDS) survey was first conducted to identify profiles of drug use and HIV risk-related behaviour among PWID. A sample of PWID was then included in a one-year cohort study to describe access to methadone treatment and associated factors. Among the 603 patients enrolled in the RDS survey, 10% were female, all were injecting heroin and 24% were using methamphetamine, including 3 (0.5%) through injection. Different profiles of risk-related behaviours were identified, including one entailing high-risk sexual behaviour (n=37) and another involving drug-related high-risk practices (n=22). High-risk sexual activity was related to binge drinking and methamphetamine use. Among subjects with low sexual risk, sexual intercourse with a main partner with unknown serostatus was often unprotected. Among the 250 PWID included in the cohort, 55.2% initiated methadone treatment during the follow-up (versus 4.4% at RDS); methamphetamine use significantly increased. The factors associated with not being treated with methadone after 52 weeks were fewer injections per month and being a methamphetamine user at RDS. Heroin is still the main drug injected in Haiphong. Methamphetamine use is increasing markedly and is associated with delay in methadone initiation. Drug-related risks are low but sexual risk behaviours are still present. Comprehensive approaches are needed in the short term. Copyright © 2017 Elsevier B.V. All rights reserved.

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

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Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

2017-07-01

The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

Addiction and treatment experiences among active methamphetamine users recruited from a township community in Cape Town, South Africa: A mixed-methods study.

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Meade, Christina S; Towe, Sheri L; Watt, Melissa H; Lion, Ryan R; Myers, Bronwyn; Skinner, Donald; Kimani, Stephen; Pieterse, Desiree

2015-07-01

Since 2000, there has been a dramatic increase in methamphetamine use in South Africa, but little is known about the experiences of out-of-treatment users. This mixed-methods study describes the substance use histories, addiction symptoms, and treatment experiences of a community-recruited sample of methamphetamine users in Cape Town. Using respondent driven sampling, 360 methamphetamine users (44% female) completed structured clinical interviews to assess substance abuse and treatment history and computerized surveys to assess drug-related risks. A sub-sample of 30 participants completed in-depth interviews to qualitatively explore experiences with methamphetamine use and drug treatment. Participants had used methamphetamine for an average of 7.06 years (SD=3.64). They reported using methamphetamine on an average of 23.49 of the past 30 days (SD=8.90); 60% used daily. The majority (90%) met ICD-10 criteria for dependence, and many reported severe social, financial, and legal consequences. While only 10% had ever received drug treatment, 90% reported that they wanted treatment. In the qualitative interviews, participants reported multiple barriers to treatment, including beliefs that treatment is ineffective and relapse is inevitable in their social context. They also identified important motivators, including desires to be drug free and improve family functioning. This study yields valuable information to more effectively respond to emerging methamphetamine epidemics in South Africa and other low- and middle-income countries. Interventions to increase uptake of evidence-based services must actively seek out drug users and build motivation for treatment, and offer continuing care services to prevent relapse. Community education campaigns are also needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice.

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Mendieta, Liliana; Granado, Noelia; Aguilera, José; Tizabi, Yousef; Moratalla, Rosario

2016-08-01

The C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) is a nontoxic peptide with demonstrated in vitro and in vivo neuroprotective effects against striatal dopaminergic damage induced by 1-methyl-4-phenylpyridinium and 6-hydoxydopamine, suggesting its possible therapeutic potential in Parkinson's disease. Methamphetamine, a widely abused psychostimulant, has selective dopaminergic neurotoxicity in rodents, monkeys, and humans. This study was undertaken to determine whether Hc-TeTx might also protect against methamphetamine-induced dopaminergic neurotoxicity and the consequent motor impairment. For this purpose, we treated mice with a toxic regimen of methamphetamine (4mg/kg, 3 consecutive i.p. injections, 3 hours apart) followed by 3 injections of 40 ug/kg of Hc-TeTx into grastrocnemius muscle at 1, 24, and 48 hours post methamphetamine treatment. We found that Hc-TeTx significantly reduced the loss of dopaminergic markers tyrosine hydroxylase and dopamine transporter and the increases in silver staining (a well stablished degeneration marker) induced by methamphetamine in the striatum. Moreover, Hc-TeTx prevented the increase of neuronal nitric oxide synthase but did not affect microglia activation induced by methamphetamine. Stereological neuronal count in the substantia nigra indicated loss of tyrosine hydroxylase-positive neurons after methamphetamine that was partially prevented by Hc-TeTx. Importantly, impairment in motor behaviors post methamphetamine treatment were significantly reduced by Hc-TeTx. Here we demonstrate that Hc-TeTx can provide significant protection against acute methamphetamine-induced neurotoxicity and motor impairment, suggesting its therapeutic potential in methamphetamine abusers. © The Author 2016. Published by Oxford University Press on behalf of CINP.

A Qualitative Exploration of Trajectories among Suburban Users of Methamphetamine

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Boeri, Miriam Williams; Harbry, Liam; Gibson, David

2009-01-01

The goal of this exploratory study was to gain a better understanding of methamphetamine use among suburban users. We know very little about the mechanisms of initiation and trajectory patterns of methamphetamine use among this under-researched and hidden population. This study employed qualitative methods to examine the drug career of suburban…

Clinical Characteristics of Fatal Methamphetamine-related Stroke: A National Study.

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Darke, Shane; Lappin, Julia; Kaye, Sharlene; Duflou, Johan

2018-05-01

The study aimed to determine the clinical characteristics of fatal methamphetamine-related stroke in Australia, 2009-2015. There were 38 cases, 60.5% male, with a mean age of 40.3 years. In no case was there evidence that this was the first time methamphetamine had been used by the decedent, and 52.6% had known histories of injecting drug use. The stroke was hemorrhagic in 37 of 38 cases. In 21.1% of cases, the stroke was purely parenchymal and, in 18.4%, involved purely the subarachnoid space. A ruptured berry aneurysm was present in 31.6% and in 68.8% of initial subarachnoid hemorrhages. There was evidence of systemic hypertension in 8 of 25 cases in which full autopsy findings were available. With increased use of methamphetamine, there is a high probability of increased hemorrhagic stroke incidence among young people. In cases of fatal hemorrhagic stroke among young cases presenting to autopsy, the possibility of methamphetamine use should be borne in mind. © 2017 American Academy of Forensic Sciences.

Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats Exposed Prenatally and/or Postnatally to Methamphetamine

Czech Academy of Sciences Publication Activity Database

Šírová, J.; Krištofíková, Z.; Vrajová, M.; Fujakova-Lipski, M.; Řípová, D.; Klaschka, Jan; Šlamberová, R.

2016-01-01

Roč. 41, č. 8 (2016), s. 1911-1923 ISSN 0364-3190 Grant - others:GA MŠk(CZ) ED2.1.00/03.0078; GA ČR(CZ) GA14-03708S; Univerzita Karlova(CZ) Prvouk P34; GA UK(CZ) 88315; SVV(CZ) 260277/2016 Institutional support: RVO:67985807 Keywords : methamphetamine * dopamine transporte * sex differences * membrane fluidity Subject RIV: FH - Neurology Impact factor: 2.581, year: 2016

Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys.

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Banks, Matthew L; Blough, Bruce E

2015-08-01

Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

Science.gov (United States)

Galinato, Melissa H.; Orio, Laura; Mandyam, Chitra D.

2014-01-01

Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in

Correlates of methamphetamine use among young Iranians: Findings of a population-based survey in 2013.

Science.gov (United States)

Bagheri, Nahid; Mirzaee, Moghaddameh; Jahani, Yunes; Karamouzian, Mohammad; Sharifi, Hamid

2017-10-01

Methamphetamine use remains an important public health concern among young people across various international settings. The present study is aimed at investigating the correlates of methamphetamine use among young Iranians within the general population. This study was carried out in 13 provinces of Iran in 2013. Through multistage sampling, 3,246 young adults (aged 19-29 years) were recruited in the study. Weighted multilevel logistic regression methods were applied to identify the correlates of methamphetamine use. The lifetime prevalence of methamphetamine use was 7.1% (95% Confidence Interval (CI): 5.4, 8.8). In the multivariable logistic regression, gender (Adjusted Odds Ratio (AOR): 2.57, 95%CI: 1.37, 4.82), marital status (AOR: 4.91, 95%CI: 2.26, 10.7), education level (AOR: 2.56, 95%CI: 1.3, 5.06), profession (AOR: 2.64, 95%CI: 1.63, 4.29), overall knowledge level of methamphetamine use (AOR: 0.55, 95%CI: 0.39, 0.76), knowing a methamphetamine user among family members or friends (AOR: 2.57, 95%CI: 1.71, 4.42), knowing an ecstasy user among family members or friends (AOR: 3.36, 95%CI: 1.92, 5.9), and extramarital sex (AOR: 6.29, 95%CI: 4.29, 9.22) were significantly associated with methamphetamine use. The lifetime prevalence of methamphetamine use among young Iranian adults is concerning. Educational settings should be equipped with the required resources to take a proactive role in educating adolescents and young adults on substance use including methamphetamine. This study was done on a national level and identified the factors that can correlate with methamphetamine use. Its results can be very useful for policy decision makers. (Am J Addict 2017;26:731-737). © 2017 American Academy of Addiction Psychiatry.

National Case-Control Study of Homicide Offending and Methamphetamine Use

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Stretesky, Paul B.

2009-01-01

The purpose of this study is to examine the relationship between methamphetamine use and homicide. To carry out this study, data from the National Household Survey on Drug Abuse and Survey of Inmates in State and Federal Correctional Facilities were combined to create a case-control design. The main exposure measure is methamphetamine use and the…

Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure.

Science.gov (United States)

Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

2016-06-01

Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131-141, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Methamphetamine use and treatment in Iran: A systematic review from the most populated Persian Gulf country.

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Alam-mehrjerdi, Zahra; Mokri, Azarakhsh; Dolan, Kate

2015-08-01

Methamphetamine use is a new health concern in Iran, the most populated Persian Gulf country. However, there is no well-documented literature. The current study objectives were to systematically review all published English and Persian studies of the prevalence of methamphetamine use, the general physical and psychiatric-related harms and the availability of methamphetamine treatment and harm reduction services for adult users in Iran. A comprehensive search of the international peer-reviewed and gray literature was undertaken. Multiple electronic and scientific English and Persian databases were systematically searched from January 2002 to September 2014. Additionally, English and Persian gray literature on methamphetamine use was sought using online gray literature databases, library databases and general online searches over the same period of time. Nineteen thousand and two hundred and eight studies, reports and conference papers were identified but only 42 studies were relevant to the study objectives. They were mainly published in 2010-2014. The search results confirmed the seizures of methamphetamine (six studies), the prevalence of methamphetamine use among the general population (three studies), drug users (four studies), women (nine studies) and opiate users in opiate treatment programs (five studies). In addition, methamphetamine use had resulted in blood-borne viral infections (one study), psychosis and intoxication (ten studies). Different reasons had facilitated methamphetamine use. However, the Matrix Model, community therapy and harm reduction services (four studies) had been provided for methamphetamine users in some cities. The current situation of methamphetamine use necessitates more research on the epidemiology and health-related implications. These studies should help in identifying priorities for designing and implementing prevention and educational programs. More active models of engagement with Persian methamphetamine users and the

The impact of methamphetamine use on subjective well-being in an Internet survey: preliminary findings.

Science.gov (United States)

Looby, Alison; Earleywine, Mitch

2007-04-01

Methamphetamine is one of the most widely used stimulants worldwide. Common reasons for use of the drug include efforts to improve or enhance one's life and to uplift one's mood. Nevertheless, acute effects of the drug lead to temporary improvements in mood followed by negative affect. The purpose of the present study was to expand on the current literature and examine other aspects of mood and satisfaction with life in methamphetamine users. Over 6000 adults completed an Internet survey and reported on depression, apathy, satisfaction with life, happiness, and subjective well-being, in addition to measures of methamphetamine use. We compared those who had used methamphetamine at least once within the past year (N = 610) to those who had never used (N = 6063). Methamphetamine use accounted for significant variance in depression, apathy, satisfaction with life, happiness, and subjective well-being even when alcohol and other drugs served as covariates. Methamphetamine use may decrease one's subjective well-being instead of enhancing it, which is contradictory to the perceptions of many users. Increasing awareness about methamphetamine's negative impact on mood and life satisfaction might help decrease prevalence of the drug's use and associated troubles. Copyright 2007 John Wiley & Sons, Ltd.

Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

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Prenatal Methamphetamine Exposure Linked with Problems

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice

International Nuclear Information System (INIS)

Mizugaki, Michinao; Hishinuma, Takanori; Nakamura, Hitoshi

1993-01-01

[ 11 C]Methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [ 11 C]CH 3 I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [ 11 C]methamphetamine was investigated in the mice brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [ 11 C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [ 11 C]methamphetamine. (Author)

Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice

International Nuclear Information System (INIS)

Mizugaki, Michinao; Hishinuma, Takanori; Nakamura, Hitoshi

1993-01-01

[ 11 C]methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [ 11 C]CH 3 I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [ 11 C]methamphetamine was investigated in the mouse brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [ 11 C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [ 11 C]methamphetamine. (author)

Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo.

Science.gov (United States)

Kaushal, Nidhi; Seminerio, Michael J; Robson, Matthew J; McCurdy, Christopher R; Matsumoto, Rae R

2013-08-01

Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it "acts in part as an agonist." SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative σ receptor antagonist with nanomolar affinity and selectivity for σ receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established σ receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate σ receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Initial Feasibility and Acceptability of a Comprehensive Intervention for Methamphetamine-Using Pregnant Women in South Africa

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Hendrée E. Jones

2014-01-01

Full Text Available The purpose of the present study was to determine the feasibility, acceptability, and initial efficacy of a women-focused intervention addressing methamphetamine use and HIV sexual risk among pregnant women in Cape Town, South Africa. A two-group randomized pilot study was conducted, comparing a women-focused intervention for methamphetamine use and related sexual risk behaviors to a psychoeducational condition. Participants were pregnant women who used methamphetamine regularly, had unprotected sex in the prior month, and were HIV-negative. Primary maternal outcomes were methamphetamine use in the past 30 days, frequency of unprotected sexual acts in the past 30 days, and number of antenatal obstetrical appointments attended. Primary neonatal outcomes were length of hospital stay, birth weight, and gestational age at delivery. Of the 57 women initially potentially eligible, only 4 declined to participate. Of the 36 women who were eligible and enrolled, 92% completed all four intervention sessions. Women in both conditions significantly reduced their methamphetamine use and number of unprotected sex acts. Therefore, delivering comprehensive interventions to address methamphetamine use and HIV risk behaviors among methamphetamine-using pregnant women is feasible in South Africa. Further testing of these interventions is needed to address methamphetamine use in this vulnerable population.

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

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Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

2017-07-01

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Counterpublic health and the design of drug services for methamphetamine consumers in Melbourne.

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Duff, Cameron; Moore, David

2015-01-01

This article is interested in how notions of the 'public' are conceived, marshalled and enacted in drug-treatment responses to methamphetamine use in Melbourne, Australia. After reviewing qualitative data collected among health-care providers and methamphetamine consumers, we draw on the work of Michael Warner to argue that services for methamphetamine consumers in Melbourne betray ongoing tensions between 'public' and 'counterpublic' constituencies. Our analysis indicates that these tensions manifest in two ways: in the management of 'street business' in the delivery of services and in negotiating the meaning of health and the terms of its restoration or promotion. Reflecting these tensions, while the design of services for methamphetamine consumers is largely modelled on public health principles, the everyday experience of these services may be more accurately characterised in terms of what Kane Race has called 'counterpublic health'. Extending Race's analysis, we conclude that more explicit focus on the idea of counterpublic health may help local services engage with methamphetamine consumers in new ways, providing grounds for novel outreach, harm-reduction and treatment strategies. © The Author(s) 2014.

COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence

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C. A. Bousman

2010-01-01

Full Text Available Catechol-O-methyltransferease (COMT metabolizes prefrontal cortex dopamine (DA, a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior.

Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice

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Mizugaki, Michinao; Hishinuma, Takanori; Nakamura, Hitoshi (Tohoku University Hospital, Sendai (Japan). Dept. of Pharmaceutical Sciences) (and others)

1993-05-01

[[sup 11]C]methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [[sup 11]C]CH[sub 3]I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [[sup 11]C]methamphetamine was investigated in the mouse brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [[sup 11]C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [[sup 11]C]methamphetamine. (author).

Drug assertiveness and sexual risk-taking behavior in a sample of HIV-positive, methamphetamine-using men who have sex with men.

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Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; McQuaid, John R; Patterson, Thomas L

2011-10-01

Drug assertiveness skills have been demonstrated to be effective in reducing substance use behaviors among patients with alcohol or heroin use disorders. This study examined the association between drug assertiveness and methamphetamine use, psychological factors, and sexual risk behaviors in a sample of 250 HIV-positive men who have sex with men enrolled in a safer sex intervention in San Diego, CA. Less assertiveness in turning down drugs was associated with greater frequency and larger amounts of methamphetamine use, lower self-esteem, higher scores on a measure of sexual sensation seeking, and greater attendance at risky sexual venues. These data suggest that drug assertiveness training should be incorporated into drug abuse treatment programs and other risk reduction interventions for methamphetamine users. Copyright © 2011 Elsevier Inc. All rights reserved.

Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse

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Mata, Mariana M.; Napier, T. Celeste; Graves, Steven M.; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L.

2015-01-01

The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the comorbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n = 18) or be given saline (control; n = 16) for 14 days. One day after the last self-administration session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γand TNF-α, and frequencies of CD4+, CD8+, CD200+ and CD11b/c+ lymphocytes in the spleen. Rats that self-administer methamphetamine had a lower frequency of CD4+ T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4+ T cells. Methamphetamine using rats had a higher frequency of CD8+ T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Or data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why African American men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection. PMID:25678251

Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse.

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Mata, Mariana M; Napier, T Celeste; Graves, Steven M; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L

2015-04-05

The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4(+), CD8(+), CD200(+) and CD11b/c(+) lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4(+) T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4(+) T cells. Methamphetamine using rats had a higher frequency of CD8(+) T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: Implications for methamphetamine-mediated neurotoxicity

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Zhang, Yuan; Shen, Kai; Bai, Ying; Lv, Xuan; Huang, Rongrong; Zhang, Wei; Chao, Jie; Nguyen, Lan K.; Hua, Jun; Gan, Guangming; Hu, Gang; Yao, Honghong

2016-01-01

ABSTRACT BBC3 (BCL2 binding component 3) is a known apoptosis inducer; however, its role in microglial survival remains poorly understood. In addition to the classical transcription factor TRP53, Mir143 is involved in BBC3 expression at the post-transcriptional level. Here, we identify unique roles of Mir143-BBC3 in mediating microglial survival via the regulation of the interplay between apoptosis and autophagy. Autophagy inhibition accelerated methamphetamine-induced apoptosis, whereas autophagy induction attenuated the decrease in microglial survival. Moreover, anti-Mir143-dependent BBC3 upregulation reversed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-Mir143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous Mir143+/− mice. These findings provide new insight regarding the specific contributions of Mir143-BBC3 to microglial survival in the context of drug abuse. PMID:27464000

The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress

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2005-07-01

K. (1995) Methamphetamine -induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents...glutamate receptors is protective against methamphetamine neurotoxicity . JNeurosci 22, 2135-2141. Beer R., Franz G., Srinivasan A., Hayes R. L., Pike B. R...1992) The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole

During-Treatment Outcomes among Female Methamphetamine-Using Offenders in Prison-Based Treatments

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Rowan-Szal, Grace A.; Joe, George W.; Simpson, D. Dwayne; Greener, Jack M.; Vance, Jerry

2009-01-01

An increasingly important treatment group is the expanding population of methamphetamine-using female offenders. This study focused on women methamphetamine-using offenders (n = 359) who were treated either in a modified therapeutic community (TC) program ("Clean Lifestyle is Freedom Forever" [CLIFF]-TC: n = 234) designed for non-violent offenders…

Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

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Musshoff, F

2000-02-01

The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

Eating high-fat chow enhances sensitization to the effects of methamphetamine on locomotion in rats.

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McGuire, Blaine A; Baladi, Michelle G; France, Charles P

2011-05-11

Eating high-fat chow can modify the effects of drugs acting directly or indirectly on dopamine systems and repeated intermittent drug administration can markedly increase sensitivity (i.e., sensitization) to the behavioral effects of indirect-acting dopamine receptor agonists (e.g., methamphetamine). This study examined whether eating high-fat chow alters the sensitivity of male Sprague Dawley rats to the locomotor stimulating effects of acute or repeated administration of methamphetamine. The acute effects of methamphetamine on locomotion were not different between rats (n=6/group) eating high-fat or standard chow for 1 or 4 weeks. Sensitivity to the effects of methamphetamine (0.1-10mg/kg, i.p.) increased progressively across 4 once per week tests; this sensitization developed more rapidly and to a greater extent in rats eating high-fat chow as compared with rats eating standard chow. Thus, while eating high-fat chow does not appear to alter sensitivity of rats to acutely-administered methamphetamine, it significantly increases the sensitization that develops to repeated intermittent administration of methamphetamine. These data suggest that eating certain foods influences the development of sensitization to drugs acting on dopamine systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Protective Effect of Coenzyme Q10 on Methamphetamine-Induced Apoptosis in Adult Male Rats

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Fatemeh Gholipour

2017-06-01

Full Text Available Background: The negative consequence of methamphetamine abuse is due to neuropathologic changes in the brain, which reduces dopaminergic neurons and result in damage to different brain areas. Neurotoxicity induced by methamphetamine increases the oxidative stress and associated with neuronal apoptosis. The role of the antioxidant coenzyme Q10 probably produces its neuroprotective effects. Therefore, the purpose of the present study was to examine the protective effect of coenzyme Q10 on methamphetamine-induced apoptosis in adult male rats.Materials and Methods: Fifty Wistar eight-week adult rats randomly divided into 5 groups: Healthy control, methamphetamine injection (Meth, methamphetamine injection and CoQ10 5mg/kg treatment (Meth+Post CoQ10 5mg/kg, methamphetamine injection and CoQ10 10mg/kg treatment (Meth+Post CoQ10 10mg/kg, methamphetamine injection and CoQ10 20mg/kg treatment (Meth+Post CoQ10 20mg/kg. Methamphetamine with a purity of 96% with a dosage of 20 mg/kg was injected Intraperitoneal. Coenzyme Q10 for three treatment groups was injected intraperitoneally for 14 days in a dosage of 5, 10 and 20 mg/kg/day. The protein expressions of Baxand Bcl2 were evaluated by western blotting technique.Results: Bax protein expression was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.010 and so Meth+Post CoQ10 10mg/kg (p=0.004 comparing to Meth group. In addition, Bcl2 protein expression was significantly higher in Meth+Post CoQ10 5mg/kg comparing to Meth group (p=0.018. However, there were no significant differences between control and CoQ10 treatment groups. Bax/Bcl2 ratio was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.005, Meth+Post CoQ10 10mg/kg (p=0.008 and Meth+Post CoQ10 20mg/kg (p=0.044 comparing to Meth group.Conclusion: We suggest that CoQ10 reduces the methamphetamine-induced apoptosis in the striatum of the rats through the reduction of apoptotic factors and increase of anti-apoptotic pathways.

Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice.

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Yu, Lu-lu; Wang, Xue-yi; Zhao, Mei; Liu, Yu; Li, Yan-qin; Li, Fang-qiong; Wang, Xiaoyi; Xue, Yan-xue; Lu, Lin

2009-06-01

Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory. The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP). Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration. Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation. Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

Simultaneous use of alcohol with methamphetamine but not ecstasy linked with aggression among young adult stimulant users.

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Leslie, Ellen M; Smirnov, Andrew; Cherney, Adrian; Wells, Helene; Legosz, Margot; Kemp, Robert; Najman, Jake M

2017-07-01

Illicit stimulants are often combined with alcohol in nightlife entertainment districts, an environment where aggressive behaviour commonly occurs. While alcohol and methamphetamine use are each associated with aggressive behaviour, relatively little is known about the impact of the combined use of alcohol and amphetamine-type stimulants (i.e., ecstasy [MDMA] and methamphetamine) on aggression. Analysis of longitudinal data from a population-based sample of Australian young adult amphetamine-type stimulant users (n=248) to examine: (a) prevalence and timing of simultaneous alcohol and amphetamine-type stimulant use and (b) predictors of ecstasy- and methamphetamine-related aggression and hostility. Prediction models of ecstasy- and methamphetamine-related aggression and hostility were developed using multivariate logistic regression. Simultaneous alcohol consumption and amphetamine-type stimulant use was prevalent, with drinking generally occurring before consuming amphetamine-type stimulants and while 'high'. Methamphetamine-related aggression and hostility was significantly associated with recurrent risky simultaneous methamphetamine and alcohol use (Adjusted Odds Ratio [AOR] 2.74, 95% CI 1.09-6.89), a high frequency and increasing use methamphetamine trajectory (AOR 7.23, 95% CI 1.27-41.03), and high trait aggression (AOR 5.78, 95% CI 2.53-13.20). In contrast, only trait aggression (moderate: AOR 3.01, 95% CI 1.55-5.84; high: AOR 5.02, 95% CI 2.38-10.61) was associated with ecstasy-related aggression and hostility. These findings indicate a link between risky patterns of simultaneous alcohol and methamphetamine use and methamphetamine-related aggression and hostility, independent of separate use of alcohol, methamphetamine and cannabis, trait aggression, psychosis, and gender. The policy challenges of amphetamine-type stimulant and alcohol use require a targeted, multidisciplinary approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of crystal methamphetamine among male adolescents in Cape Town, South Africa: Caregivers' experiences.

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Asante, Kwaku Oppong; Lentoor, Antonio G

2017-03-27

Against the background that crystal methamphetamine (colloquially known as "tik") is extensively used by the emerging working class Coloured youth in Cape Town, South Africa, this exploratory qualitative study was conducted to explore the experience of mothers whose children use methamphetamine. The researchers conducted one-to-one semi-structured in-depth interviews with sixteen (16) purposively selected caregivers (mothers) whose sons use methamphetamine. Interviews were recorded and simultaneously translated and transcribed. Thematic analysis was used to identify themes related to the experiences of caregivers of youth with methamphetamine problems. Findings showed that youth misbehaviour provided a context that led to feelings of shame and embarrassment. Participants also experienced personal challenges which included emotional problems, fear and self-blame. Participants also expressed family disruptions and financial drain as adverse experiences as a results of their sons' misbehaviour. The study results highlight the psychosocial challenges for caregivers of children who use methamphetamine. These findings underscore the need for effort to be directed at the development of formal support interventions for mothers of youth who are troubled with addiction.

Evaluation of methamphetamine-associated socioeconomic status and addictive behaviors, and their impact on oral health.

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Rommel, Niklas; Rohleder, Nils H; Wagenpfeil, Stefan; Haertel-Petri, Roland; Kesting, Marco R

2015-11-01

Chronic methamphetamine abuse can lead to multiple health hazards. In particular, the substance is associated with devastating effects on oral health including symptoms such as rampant caries, gingiva inflammation, and xerostomia, whereby the term "Meth Mouth" occurs in the current literature. However, "Meth Mouth" pathology is primarily described on the basis of individual cases or has been evaluated without consideration of the mass of potential influencing factors. Therefore, we have conducted a systematic study to investigate the effects of accompanying factors and circumstances on oral health in cases of chronic methamphetamine abuse. In cooperation with two centers for addiction medicine, we assessed the data of 100 chronic methamphetamine users and 100 matched-pair controls between March 2012 and November 2013. We investigated their socioeconomic status, details of methamphetamine consumption behavior, collateral consumption of sugar beverages, nicotine alcohol, and other addictive substances including cannabis, opioids, other stimulants, and hallucinogens, and dental care. We found considerably greater unstable social circumstances, a high collateral consumption of substances with pathogenic potential for the stomatognathic system, and significantly poorer dental care in the methamphetamine-user group. Various factors have to be considered with regard to methamphetamine use and its influence on oral health. These factors can trigger potential damage by the drug methamphetamine possibly leading to the symptoms of "Meth Mouth", and should be considered in prevention and therapy strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Provigil (Modafinil) Plus Cognitive Behavioral Therapy for Methamphetamine Use in HIV+ Gay Men: A Pilot Study

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McElhiney, Martin C.; Rabkin, Judith G.; Rabkin, Richard; Nunes, Edward V.

2015-01-01

Objectives To evaluate the efficacy of modafinil combined with cognitive behavioral therapy (CBT) for treatment of methamphetamine (MA) dependence among HIV+ gay men. Methods In a single blind trial, modafinil was administered for 12 weeks, followed by a 4-week placebo phase. CBT was conducted for 18 sessions over the 16-week study. Primary outcome measures were self-reported use of days per week plus urine toxicology assays. Additional measures included the Beck Depression Inventory, Cravings Scale, and O/C Crystal Use Scale. Response was defined as > 50% decline in days used per week. Thirteen patients were enrolled over an 18-month period. Results Ten patients (77%) completed the trial, although two discontinued modafinil due to side effects. Six of the ten study completers reduced their MA use by > 50%. Conclusions These preliminary results suggest good retention using combined medication and psychotherapy, and support further examination of modafinil and CBT in double-blind placebo controlled trials. PMID:19152204

Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used?

Czech Academy of Sciences Publication Activity Database

Šlamberová, R.; Pometlová, M.; Macúchová, E.; Nohejlová, K.; Stuchlík, Aleš; Valeš, Karel

2015-01-01

Roč. 292, Oct 1 (2015), s. 361-369 ISSN 0166-4328 Grant - others:GA ČR(CZ) GA14-03708S; GA MZd(CZ) NT14484 Institutional support: RVO:67985823 Keywords : drug abuse * prenatal exposure * methamphetamine * anxiety * elevated plus-maze * social interaction text * ultrasound vocalization Subject RIV: FH - Neurology Impact factor: 3.002, year: 2015

A Multivariate Analysis of the Sociodemographic Predictors of Methamphetamine Production and Use

Science.gov (United States)

Armstrong, Todd A.; Armstrong, Gaylene S.

2013-01-01

To date, research testing the community characteristics associated with methamphetamine production and use has found that the community-level sociodemographic predictors of methamphetamine production and use vary from those of drug use in general. In this study, the authors furthered the research in this area using data from all 102 counties in…

Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

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... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

[Underlying Mechanisms of Methamphetamine-Induced Self-Injurious Behavior and Lethal Effects in Mice].

Science.gov (United States)

Mori, Tomohisa; Sawaguchi, Toshiko

2018-01-01

Relatively high doses of psychostimulants induce neurotoxicity on the dopaminergic system and self-injurious behavior (SIB) in rodents. However the underlying neuronal mechanisms of SIB remains unclear. Dopamine receptor antagonists, N-methyl-D-aspartic acid (NMDA) receptor antagonists, Nitric Oxide Synthase (NOS) inhibitors and free radical scavengers significantly attenuate methamphetamine-induced SIB. These findings indicate that activation of dopamine as well as NMDA receptors followed by radical formation and oxidative stress, especially when mediated by NOS activation, is associated with methamphetamine-induced SIB. On the other hand, an increase in the incidence of polydrug abuse is a major problem worldwide. Coadministered methamphetamine and morphine induced lethality in more than 80% in mice, accompanied by an increase in the number of poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine were significantly attenuated by pretreatment with a phospholipase A2 inhibitor or a radical scavenger, or by cooling of body from 30 to 90 min after drug administration. These results suggest that free radicals play an important role in the increased lethality induced by the coadministration of methamphetamine and morphine. Therefore, free radical scavengers and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine. These findings may help us better understand for masochistic behavior, which is a clinical phenomenon on SIB, as well as polydrug-abuse-induced acute toxicity.

Effects of methamphetamine administration on information gathering during probabilistic reasoning in healthy humans.

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Ermakova, Anna O; Ramachandra, Pranathi; Corlett, Philip R; Fletcher, Paul C; Murray, Graham K

2014-01-01

Jumping to conclusions (JTC) during probabilistic reasoning is a cognitive bias repeatedly demonstrated in people with schizophrenia and shown to be associated with delusions. Little is known about the neurochemical basis of probabilistic reasoning. We tested the hypothesis that catecholamines influence data gathering and probabilistic reasoning by administering intravenous methamphetamine, which is known to cause synaptic release of the catecholamines noradrenaline and dopamine, to healthy humans whilst they undertook a probabilistic inference task. Our study used a randomised, double-blind, cross-over design. Seventeen healthy volunteers on three visits were administered either placebo or methamphetamine or methamphetamine preceded by amisulpride. In all three conditions participants performed the "beads" task in which participants decide how much information to gather before making a probabilistic inference, and which measures the cognitive bias towards jumping to conclusions. Psychotic symptoms triggered by methamphetamine were assessed using Comprehensive Assessment of At-Risk Mental States (CAARMS). Methamphetamine induced mild psychotic symptoms, but there was no effect of drug administration on the number of draws to decision (DTD) on the beads task. DTD was a stable trait that was highly correlated within subjects across visits (intra-class correlation coefficients of 0.86 and 0.91 on two versions of the task). The less information was sampled in the placebo condition, the more psychotic-like symptoms the person had after the methamphetamine plus amisulpride condition (p = 0.028). Our results suggest that information gathering during probabilistic reasoning is a stable trait, not easily modified by dopaminergic or noradrenergic modulation.

An exploratory study on association between family relationship and relapse among methamphetamine users in Compulsory Treatment System of Khon Kaen and Yasothon Provinces.

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Rodseeda, Pritsana; Ratanasiri, Amornrat; Kanato, Manop; Pinitsoontorn, Somdej; Chiawiriyabunya, Isara

2010-03-01

It was estimated that 3.5 million Thais have ever used "Yaba (methamphetamine)" at least once in their entire life. The Northeastern region had the highest number of Yaba users with a high relapse rate after treatment. The authors aimed to explore the association between relapse, among methamphetamine users in the Compulsory Treatment System of Khon Kaen and Yasothon Provinces, and family relationship as well as other contextual factors. An exploratory study was conducted from all cases of post-treatment methamphetamine users in the databases of Khon Kaen Drug Dependence Treatment Center and Yasothorn Provincial Probation Office during October 2007 and February 2008. Interviews and observations were done for data collection. Double data entry was applied. Pearson Chi-square, Fisher's exact test and odds ratio were used to assess the associations. Sixty-five users were found (13 relapses and 52 abstainers). Family relationship revealed no significant association with relapse of the methamphetamine users. Other contextual factors, however, did. They were social acceptance [acceptance by community leader (p = 0.006), acceptance for working or studying (p = 0.049)], risky community situations [using Yaba of close friend, existence of Yaba users and Yaba trading in community (p = 0.014, p agent and drinking of alcohol to reduce Yaba desire (p = 0.012 and p = 0.013)]. Effect of family relationship on relapse among post-treatment methamphetamine users could not be demonstrated in the present study. But several contextual factors had significant relationship with the relapse.

Differentiating Characteristics of Juvenile Methamphetamine Users

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Fass, Daniel; Calhoun, Georgia B.; Glaser, Brian A.; Yanosky, Daniel J., II

2009-01-01

The authors investigated the differences in characteristics and risk behaviors endorsed by detained adolescent methamphetamine users and compared them with other drug users. Subjects completed the Millon Adolescent Clinical Inventory and a questionnaire in which sociodemographics and behavioral information were explored and compared. Multivariate…

Polydrug use among IDUs in Tijuana, Mexico: correlates of methamphetamine use and route of administration by gender.

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Rusch, Melanie L; Lozada, Remedios; Pollini, Robin A; Vera, Alicia; Patterson, Thomas L; Case, Patricia; Strathdee, Stefanie A

2009-09-01

Tijuana is situated on the Mexico-USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006-2007, IDUs > or =18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression was used to assess associations with methamphetamine use (past 6 months), stratified by gender. Among 1,056 participants, methamphetamine use was more commonly reported among females compared to males (80% vs. 68%, p 35 years (AOR, 0.2; 95% CI, 0.1-0.6) was associated with methamphetamine use. Among males (N = 898), being aged >35 years (AOR, 0.5; 95% CI, 0.3-0.6), homeless (AOR, 1.4 (0.9-2.2)), and ever reporting sex with another male (MSM; AOR, 1.9; 95% CI, 1.4-2.7) were associated with methamphetamine use. Among males, a history of MSM was associated with injection, while sex trade and >2 casual sex partners were associated with multiple routes of administration. HIV was higher among both males and females reporting injection as the only route of methamphetamine administration. Methamphetamine use is highly prevalent among IDUs in Tijuana, especially among females. Routes of administration differed by gender and subgroup which has important implications for tailoring harm reduction interventions and drug abuse treatment.

Detection of methamphetamine in the presence of nicotine using in situ chemical derivatization and ion mobility spectrometry.

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Ochoa, Mariela L; Harrington, Peter B

2004-02-15

The detection of methamphetamine in the presence of nicotine has been successfully accomplished using in situ chemical derivatization with propyl chloroformate as the derivatization reagent and ion mobility spectrometry (IMS). The rapid detection of methamphetamine is important for forensic scientists in order to establish a chain of evidence and link criminals to the crime scene. Nicotine is pervasive in clandestine drug laboratories from cigarette smoke residue. It has been demonstrated that nicotine obscures the methamphetamine peaks in ion mobility spectrometers due to their similar charge affinities and ion mobilities, which makes their detection a challenging task. As a consequence, false positive or negative responses may arise. In situ chemical derivatization poses as a sensitive, accurate, and reproducible alternative to remove the nicotine background when detecting nanogram amounts of methamphetamine. The derivatization agent was coated onto the sample disk, and the derivatization product corresponding to propyl methamphetamine carbamate was detected. In the present study, in situ chemical derivatization was demonstrated to be a feasible method to detect methamphetamine hydrochloride as the carbamate derivative, which was baseline-resolved from the nicotine peak. Alternating least squares (ALS) was used to model the datasets. A mixture containing both compounds revealed reduced mobilities of 1.61 cm(2)/V.s and 1.54 cm(2)/V.s for methamphetamine and nicotine, respectively. The reduced mobility of propyl methamphetamine carbamate was found at 1.35 cm(2)/V.s.

Tips for Teens: The Truth about Methamphetamine

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... who take meth can become paranoid, confused,and aggressive;they can die from overheating and convulsions. 5 ... is a powerfully addictive drug that can cause aggression and violent or psychotic behavior. 1 Methamphetamine is ...

Assessment of tolerance to the effects of methamphetamine on daytime and nighttime activity evaluated with actigraphy in rhesus monkeys.

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Berro, Laís F; Andersen, Monica L; Howell, Leonard L

2017-08-01

Methamphetamine is one of the most largely consumed illicit drugs, and its use is associated with abuse liability and several adverse health effects, such as sleep impairment. Importantly, sleep quality can influence addiction treatment outcomes. Evidence suggests that tolerance can develop to the sleep-disrupting effects of stimulant drugs. The aim of the present study was to investigate the development of tolerance to the actigraphy-based sleep-disrupting and stimulant effects of methamphetamine self-administration in rhesus monkeys. Methamphetamine (0.03 mg/kg/inf, i.v.) self-administration was carried out following three different protocols: 14 consecutive days of self-administration, 5 days/week for 3 weeks, with a 2-day interval between 5-day blocks of self-administration, and 3 days/week for 3 weeks, with a 4-day interval between 3-day blocks of self-administration. Daytime activity and activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline parameters) and throughout each protocol. Methamphetamine self-administration markedly disrupted sleep-like measures and increased daytime activity. Tolerance developed to those effects with repeated methamphetamine intake exceeding five consecutive days. Inclusion of washout periods (2 or 4 days) between blocks of methamphetamine self-administration attenuated the development of tolerance, with longer breaks from methamphetamine intake being more effective in maintaining the sleep-disrupting and stimulant effects of methamphetamine. Tolerance can develop to the stimulant and sleep-disrupting effects of methamphetamine self-administration. Interruption of drug intake extends the effects of methamphetamine on sleep-like measures and daytime activity.

GABAA receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine in rhesus monkeys.

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Berro, Laís F; Andersen, Monica L; Tufik, Sergio; Howell, Leonard L

2017-09-01

GABA A receptor positive allosteric modulators (GABA A receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABA A receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABA A receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general daytime activity were evaluated with Actiwatch monitors. Methamphetamine self-administration (0.03 mg/kg/inf) was evaluated during morning sessions. Methamphetamine-induced dopamine overflow was assessed through in vivo microdialysis targeting the nucleus accumbens. Nighttime treatment with either temazepam or eszopiclone was ineffective in improving sleep-like measures disrupted by methamphetamine self-administration. Acute pretreatment with a low dose of temazepam before self-administration sessions increased methamphetamine self-administration without affecting normal daytime home-cage activity. At a high dose, acute temazepam pretreatment decreased methamphetamine self-administration and attenuated methamphetamine-induced increases in dopamine in the nucleus accumbens, without decreasing general daytime activity. Acute eszopiclone treatment exerted no effects on methamphetamine intake or drug-induced increases in dopamine. Our study suggests that treatments based on GABA A receptor modulators are not effective for the treatment of sleep disruption in the context of psychostimulant use. In addition, distinct GABA A receptor modulators differentially modulated the abuse-related effects of methamphetamine, with acute treatment with the high efficacy GABA A receptor modulator temazepam decreasing the behavioral and neurochemical effects

Electrochemical Impedance Spectroscopic Sensing of Methamphetamine by a Specific Aptamer

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Omid Mashinchian

2012-05-01

Full Text Available Introduction: Electrochemical impedance spectroscopy (EIS is a simple and highly sensitive technique that can be used for evaluation of the aptamer-target interaction even in a label-free approach. Methods: To pursue the effectiveness of EIS, in the current study, the folding properties of specific aptamer for methamphetamine (METH (i.e., aptaMETH were evaluated in the presence of METH and amphetamine (Amph. Folded and unfolded aptaMETH was mounted on the gold electrode surface and the electron charge transfer was measured by EIS. Results: The Ret of methamphetamine-aptaMETH was significantly increased in comparison with other folding conditions, indicating specific detection of METH by aptaMETH. Conclusion: Based on these findings, methamphetamine-aptaMETH on the gold electrode surface displayed the most interfacial electrode resistance and thus the most folding situation. This clearly indicates that the aptaMETH can profoundly and specifically pinpoint METH; as a result we suggest utilization of this methodology for fast and cost-effective identification of METH.

Effect of Methamphetamine on Spectral Binding, Ligand Docking and Metabolism of Anti-HIV Drugs with CYP3A4

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Ande, Anusha; Wang, Lei; Vaidya, Naveen K.; Li, Weihua; Kumar, Santosh; Kumar, Anil

2016-01-01

Cytochrome P450 3A4 (CYP3A4) is the major drug metabolic enzyme, and is involved in the metabolism of antiretroviral drugs, especially protease inhibitors (PIs). This study was undertaken to examine the effect of methamphetamine on the binding and metabolism of PIs with CYP3A4. We showed that methamphetamine exhibits a type I spectral change upon binding to CYP3A4 with δAmax and KD of 0.016±0.001 and 204±18 μM, respectively. Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. We then studied the effect of methamphetamine binding on PIs with CYP3A4. Our results showed that methamphetamine alters spectral binding of nelfinavir but not the other type I PIs (lopinavir, atazanavir, tipranavir). The change in spectral binding for nelfinavir was observed at both δAmax (0.004±0.0003 vs. 0.0068±0.0001) and KD (1.42±0.36 vs.2.93±0.08 μM) levels. We further tested effect of methamphetamine on binding of 2 type II PIs; ritonavir and indinavir. Our results showed that methamphetamine alters the ritonavir binding to CYP3A4 by decreasing both the δAmax (0.0038±0.0003 vs. 0.0055±0.0003) and KD (0.043±0.0001 vs. 0.065±0.001 nM), while indinavir showed only reduced KD in presence of methamphetamine (0.086±0.01 vs. 0.174±0.03 nM). Furthermore, LC-MS/MS studies in high CYP3A4 human liver microsomes showed a decrease in the formation of hydroxy ritonavir in the presence of methamphetamine. Finally, CYP3A4 docking with lopinavir and ritonavir in the absence and presence of methamphetamine showed that methamphetamine alters the docking of ritonavir, which is consistent with the results obtained from spectral binding and metabolism studies. Overall, our results demonstrated differential effects of methamphetamine on the binding and metabolism of PIs with CYP3A4. These findings have clinical implication in terms of drug dose adjustment of antiretroviral medication, especially with ritonavir

Protection of methamphetamine nigrostriatal toxicity by dietary selenium.

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Kim, H C; Jhoo, W K; Choi, D Y; Im, D H; Shin, E J; Suh, J H; Floyd, R A; Bing, G

1999-12-18

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.

Unmet healthcare need among women who use methamphetamine in San Francisco.

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Powelson, Elisabeth; Lorvick, Jennifer; Lutnick, Alexandra; Wenger, Lynn; Klausner, Jeffery; Kral, Alex H

2014-02-01

Methamphetamine use has increased substantially in the United States since the 1990s. Few studies have examined the healthcare service needs of women who use methamphetamine. This study describes unmet medical needs in a community-based sample of women who use methamphetamine in San Francisco, CA. Women who use methamphetamine were recruited in San Francisco and participated in a computer-assisted survey (N = 298 HIV-negative women). Multivariate analysis was performed to explore associations among sociodemographic variables, drug use, use of health and social services, and unmet healthcare need across three domains: chronic health problems, dermatologic problems, and women's preventive healthcare. Sixty-nine percent of participants reported a need for care for a chronic health condition, and 31% of them had an unmet need for care, in the last six months. Thirty-five percent of participants reported a need for dermatologic healthcare, and 66% had an unmet need for care in the last 6 months. Ninety-two percent of participants reported a need for women's preventive healthcare and 46% had an unmet need for care in the last year. Women who reported having a healthcare provider had lower odds of reporting an unmet need for a chronic health condition or women's preventive healthcare. Women who used a case manager had lower odds of having an unmet need for dermatologic care. A significant proportion of women who use methamphetamine in this sample had an unmet need for women's preventive healthcare, and overall these women had a significant unmet need for healthcare. These findings suggest that contact with a healthcare provider or a caseworker could help to expand access to healthcare for this vulnerable population.

Combating Methamphetamine Use in the Community: The Efficacy of the Drug Court Model

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Listwan, Shelley Johnson; Shaffer, Deborah Koetzle; Hartman, Jennifer L.

2009-01-01

Methamphetamine use was historically a problem facing Western states; however, in recent years it has methodically spread throughout the nation. Methamphetamine use impacts communities, families, and the criminal justice system in a variety of ways. As such, many jurisdictions are developing policies to reduce the sale and consumption of this drug…

Local hippocampal methamphetamine-induced reinforcement

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Ulises M Ricoy

2009-11-01

Full Text Available Drug abuse and addiction are major problems in the United States. In particular methamphetamine (METH use has increased dramatically. A greater understanding of how METH acts on the brain to induce addiction may lead to better therapeutic targets for this problem. The hippocampus is recognized as an important structure in learning and memory, but is not typically associated with drug reinforcement or reward processes. Here, the focus is on the hippocampus which has been largely ignored in the addiction literature as compared to the nucleus accumbens (NAc, ventral tegmental area (VTA, and prefrontal cortex (PFC. The results show that METH administered unilaterally via a microdialysis probe to rats’ right dorsal hippocampus will induce drug-seeking (place preference and drug-taking (lever-pressing behavior. Furthermore, both of these responses are dependent on local dopamine (DA receptor activation, as they are impaired by a selective D1/D5 receptor antagonist. The results suggest that the hippocampus is part of the brain’s reward circuitry that underlies addiction.

Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo

OpenAIRE

Kaushal, Nidhi; Seminerio, Michael J.; Robson, Matthew J.; McCurdy, Christopher R.; Matsumoto, Rae R.

2012-01-01

Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it acts in part as an agonist. SN79 (6-acetyl-3-(4-(4-(4-florophenyl)...

Methamphetamine-related burns in the cornbelt.

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Burke, Bridget A; Lewis, Robert W; Latenser, Barbara A; Chung, Joseph Y; Willoughby, Clark; Kealey, G Patrick; Wibbenmeyer, Lucy A

2008-01-01

Methamphetamine (MA) is a highly addictive drug that is easily manufactured from everyday household products and chemicals found at local farm stores. The proliferation of small MA labs has led to a dramatic increase in patients sustaining thermal injury while making and/or using MA. We hypothesized that these patients have larger injuries with longer hospital stays, and larger, nonreimbursed hospital bills compared with burn patients not manufacturing or using MA. In a retrospective case-control study, all burn patients >or=16 years of age admitted to our burn center from January 2002 to December 2005 were stratified into two groups based on urine MA status. Of the 660 burn patients >or=16 years of age admitted during this 4 year period, urine drug screens were obtained at admission on 410 patients (62%); 10% of urine drug screens were MA (+). MA (+) patients have larger burns compared with MA (-) patients (9.3 vs 8.6% body surface area burns), have higher rates of inhalation injuries (20.4 vs 9.3%, P = .015), and more nonthermal trauma (13.0 vs 3.1%, P = .001). When compared with MA (-) patients, MA (+) patients require longer hospital stays (median 9.5 vs 7.0 days, P = .036), accrue greater hospital bills per day (dollars 4292 vs dollars 2797, P = .01), and lack medical insurance (66.7 vs 17.7%, P manufacture mandates that burn centers monitor patients for MA use and develop and institute protocols to ensure proper care of this increasingly costly population.

Persistent palatable food preference in rats with a history of limited and extended access to methamphetamine self-administration

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Caprioli, Daniele; Zeric, Tamara; Thorndike, Eric B; Venniro, Marco

2015-01-01

Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hr/day) or extended (6 or 9 hr/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1–0.2 mg/kg/infusion) or palatable food (5 pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5–1.0 mg/kg), following a satiety manipulation (palatable food exposure in the home cage), or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards. PMID:25582886

Persistent palatable food preference in rats with a history of limited and extended access to methamphetamine self-administration.

Science.gov (United States)

Caprioli, Daniele; Zeric, Tamara; Thorndike, Eric B; Venniro, Marco

2015-09-01

Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods, most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hours/day) or extended (6 or 9 hours/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1-0.2 mg/kg/infusion) or palatable food (five pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5-1.0 mg/kg), following a satiety manipulation (palatable food exposure in the home cage) or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards. © 2015 Society for the Study of Addiction.

Impact of Cannabinoid Receptor Ligands on Sensitisation to Methamphetamine Effects on Rat Locomotor Behaviour

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L. Landa

2008-01-01

Full Text Available The repeated administration of various drugs of abuse may lead to a gradually increased behavioural response to these substances, particularly an increase in locomotion and stereotypies may occur. This phenomenon is well known and described as behavioural sensitisation. An increased response to the drug tested, elicited by previous repeated administration of another drug is recognised as cross-sensitisation. Based on our earlier experiences with studies on mice, which confirmed sensitisation to methamphetamine and described cross-sensitisation to methamphetamine after pre-treatment with cannabinoid CB1 receptor agonist, we focused the present study on the use of another typical laboratory animal - the rat. A biological validity of the sensitisation phenomenon was expected to be enhanced if the results of both mouse and rat studies were conformable. Similar investigation in rats brought very similar results to those described earlier in mice. However, at least some interspecies differences were noted in the rat susceptibility to the development of sensitisation to methamphetamine effects. Comparing to mice, it was more demanding to titrate a dose of methamphetamine producing behavioural sensitisation. Furthermore, we were not able to provoke cross-sensitisation by repeated administration of cannabinoid CB1 receptor agonist methanandamide and similarly, we did not demonstrate the suppression of cross-sensitisation in rats that were repeatedly given combined pre-treatment with cannabinoid CB1 receptor antagonist AM 251 and methamphetamine. Finally, unlike mice, an alternative behavioural change was registered after repeated methamphetamine treatment instead: the occurrence of stereotypic behaviour (nose rubbing.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

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McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-08-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

Mental Health and Substance Use Disorder Comorbidity among Methamphetamine-Using Men Who have Sex with Men.

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Fletcher, Jesse B; Swendeman, Dallas; Reback, Cathy J

2018-04-02

Men who have sex with men (MSM) exhibit elevated rates of mental health and substance use disorder relative to their non-MSM male counterparts. Methamphetamine use in particular has been associated with both neuronal damage and mental health disorders among MSM, and this study reports on the prevalence and comorbidity of DSM-5 mental health and substance use disorders in a sample of methamphetamine-using MSM. From March 2014 through January 2015, 286 methamphetamine-using MSM enrolled in a study to reduce methamphetamine use and sexual risk behaviors. At baseline, participants demonstrated high rates of current major depressive episode (35.8%), antisocial personality disorder (23.9%), suicide risk (23.2%), obsessive-compulsive disorder (23.2%), and social phobia (20.4%), as well as methamphetamine use disorder (89.1%), marijuana use disorder (41.0%), alcohol use disorder (39.6%), cocaine use disorder (30.9%), and inhalants use disorder (15.4%). Analyses revealed significant (p disorder severity and all listed mental health disorders, as well as between alcohol use disorder and all listed mental health disorders. Mental health disorder prevalence and substance use disorder severity were both elevated, and both methamphetamine and alcohol use disorder severity were associated with increased likelihood of comorbid mental health disorder.

Assessing Environmental Prevention Strategies for Reducing the Prevalence and Associated Harms of Methamphetamine Use

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Yacoubian, George S.

2007-01-01

Developed primarily in clandestine laboratories, methamphetamine is a highly addictive synthetic drug whose physical effects include hyperactivity, euphoria, tremors, and a sense of increased energy. While the accuracy of recent accounts suggesting a methamphetamine epidemic in the United States is unclear, these reports have nevertheless…

Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

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Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

2015-06-01

Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys.

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Schwienteck, Kathryn L; Banks, Matthew L

2015-10-01

Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Family conflict and depression in HIV-negative heterosexuals: the role of methamphetamine use.

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Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; Patterson, Thomas L

2009-06-01

Previous research has reported elevated levels of depressive symptoms among methamphetamine users, but little attention has been paid to possible links between family environment and psychological distress. This study examined relationships between family conflict, substance use, and depressive symptoms in a sample of 104 heterosexual methamphetamine users in San Diego, California. Eighty-nine percent of the sample reported conflict with a family member in the past year. Conflict was reported most often with parents and siblings. Sources of conflict included drug use, lifestyle issues, interpersonal and communication issues, and concern for other family members. In regression analyses, being female, being a polydrug user, and facing social and legal stressors were associated with higher levels of family conflict. Multiple regression analyses also revealed a positive association between family conflict and depressive symptoms. Contrary to expectation, methamphetamine dose did not moderate the relationship between family conflict and depressive symptoms. Reducing family conflict may be an important first step toward ameliorating depressive symptoms and creating more supportive environments for methamphetamine users who are in urgent need of effective interventions. Copyright (c) 2009 APA, all rights reserved.

A rapid and simple screening method for methamphetamine in urine by radioimmunoassay using a 125I-labeled metahmphetamine derivative

International Nuclear Information System (INIS)

Inayama, Seiichi; Tokunaga, Yukiko; Hosoya, Eikichi; Nakadate, Teruo; Niwaguchi, Tetsukichi.

1980-01-01

N-Carboxymethylmethamphetamine, a derivative of methamphetamine, was prepared through a new synthetic pathway from ephedrine. Specific antiserum was obtained by immunization of rabbits with the conjugate of N-carboxymethylmethamphetamine with bovine serum albumin. A radioimmunoassay procedure was established using this antibody (specific for methamphetamine) and a 125 I-methamphetamine derivative. A high degree of specificity of the antibody was confirmed by testing for cross-reaction with several methamphetamine analogs, and the sensitivity was found to be 1 ng/tube. The present micro method using radioimmunoassay is highly sensitive, rapid, simple and may be useful as a micro-scale primary screening test for methamphetamine excreted in human urine, for forensic and medical purposes. (author)

Interaction and Transport of Methamphetamine and its Primary Metabolites by Organic Cation and Multidrug and Toxin Extrusion Transporters.

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Wagner, David J; Sager, Jennifer E; Duan, Haichuan; Isoherranen, Nina; Wang, Joanne

2017-07-01

Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in the United States alone. A large portion of methamphetamine and its metabolites is eliminated by the kidney with renal clearance larger than glomerular filtration clearance. Yet the mechanism of active renal secretion is poorly understood. The goals of this study were to characterize the interaction of methamphetamine and its major metabolites with organic cation transporters (OCTs) and multidrug and toxin extrusion (MATE) transporters and to identify the major transporters involved in the disposition of methamphetamine and its major metabolites, amphetamine and para -hydroxymethamphetamine ( p -OHMA). We used cell lines stably expressing relevant transporters to show that methamphetamine and its metabolites inhibit human OCTs 1-3 (hOCT1-3) and hMATE1/2-K with the greatest potencies against hOCT1 and hOCT2. Methamphetamine and amphetamine are substrates of hOCT2, hMATE1, and hMATE2-K, but not hOCT1 and hOCT3. p -OHMA is transported by hOCT1-3 and hMATE1, but not hMATE2-K. In contrast, organic anion transporters 1 and 3 do not interact with or transport these compounds. Methamphetamine and its metabolites exhibited complex interactions with hOCT1 and hOCT2, suggesting the existence of multiple binding sites. Our studies suggest the involvement of the renal OCT2/MATE pathway in tubular secretion of methamphetamine and its major metabolites and the potential of drug-drug interactions with substrates or inhibitors of the OCTs. This information may be considered when prescribing medications to suspected or known abusers of methamphetamine to mitigate the risk of increased toxicity or reduced therapeutic efficacy. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

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Ryu Jong

2010-12-01

Full Text Available Abstract Substrains of the Spontaneously Hypertensive rat (SHR, a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD, have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD. However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA test, and its response on the conditioned place preference (CPP paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj. Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine.

Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine.

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Halpin, Laura E; Collins, Stuart A; Yamamoto, Bryan K

2014-02-27

Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as 'bath salts' that have gained popularity among drug abusers. © 2013.

Cocaine, MDMA and methamphetamine residues in wastewater: Consumption trends (2009-2015) in South East Queensland, Australia.

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Lai, Foon Yin; O'Brien, Jake W; Thai, Phong K; Hall, Wayne; Chan, Gary; Bruno, Raimondo; Ort, Christoph; Prichard, Jeremy; Carter, Steve; Anuj, Shalona; Kirkbride, K Paul; Gartner, Coral; Humphries, Melissa; Mueller, Jochen F

2016-10-15

Wastewater analysis, or wastewater-based epidemiology, has become a common tool to monitor trends of illicit drug consumption around the world. In this study, we examined trends in cocaine, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine consumption by measuring their residues in wastewater from two wastewater treatment plants in Australia (specifically, an urban and a rural catchment, both in South East Queensland) between 2009 and 2015. With direct injection of the samples, target analytes were identified and quantified using liquid chromatography-mass spectrometry. Cocaine and MDMA residues and metabolites were mainly quantifiable in the urban catchment while methamphetamine residues were consistently detected in both urban and rural catchments. There was no consistent trend in the population normalised mass loads observed for cocaine and MDMA at the urban site between 2009 and 2015. In contrast, there was a five-fold increase in methamphetamine consumption over this period in this catchment. For methamphetamine consumption, the rural area showed a very similar trend as the urban catchment starting at a lower baseline. The observed increase in per capita loads of methamphetamine via wastewater analysis over the past six years in South East Queensland provides objective evidence for increased methamphetamine consumption in the Australian population while the use of other illicit stimulants remained relatively stable. Copyright © 2016 Elsevier B.V. All rights reserved.

Crazy for Ya Ba: methamphetamine use among northern Thai youth.

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Cohen, Anjalee

2014-07-01

Since the mid-1990s, Thailand has been one of the largest per capita consumers of methamphetamine pills (ya ba - "crazy drug") in the world and one of the leading consumers of methamphetamine in Southeast Asia, with its youth comprising the majority of users. This article examines the socio-cultural context of methamphetamine use among young Thai in order to understand its widespread appeal. The study is based on 18 months of ethnographic research in Chiang Mai, northern Thailand, between 2002 and 2006 and a follow-up field trip in 2011. In-depth interviews were carried out with 211 young people aged between 15 and 25 in institutional and non-institutional settings. Many of the findings derive from participant observation and informal interviews with a small sample of 20 people. Chiang Mai youth have transformed methamphetamine from a labourers' drug centred on economic utility to a multi-purpose youth drug primarily consumed for pleasure and performance. Ya ba appeals to many young Thai due to its positive image as a modern and fashionable consumer commodity, with confidence in these synthetic pills drawing on and mirroring a broader faith in modern (western) medicine. The growing demand for ya ba in northern Thailand is in part a reflection of the changing social values that have accompanied rapid urbanisation and modernisation in Thailand. In their overwhelming aspiration to be modern, young Thai are consuming ya ba not to rebel against the dominant culture, but to keep up with the demands and expectations of a modern capitalist society. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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Chaturvedi, Arvind K; Cardona, Patrick S; Soper, John W; Canfield, Dennis V

2004-07-01

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.

Correlates of Incarceration Among Young Methamphetamine Users in Chiang Mai, Thailand

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Thomson, Nicholas; Sutcliffe, Catherine G.; Sirirojn, Bangorn; Keawvichit, Rassamee; Wongworapat, Kanlaya; Sintupat, Kamolrawee; Aramrattana, Apinun

2009-01-01

Objectives. We examined correlates of incarceration among young methamphetamine users in Chiang Mai, Thailand in 2005 to 2006. Methods. We conducted a cross-sectional study among 1189 young methamphetamine users. Participants were surveyed about their recent drug use, sexual behaviors, and incarceration. Biological samples were obtained to test for sexually transmitted and viral infections. Results. Twenty-two percent of participants reported ever having been incarcerated. In multivariate analysis, risk behaviors including frequent public drunkenness, starting to use illicit drugs at an early age, involvement in the drug economy, tattooing, injecting drugs, and unprotected sex were correlated with a history of incarceration. HIV, HCV, and herpes simplex virus type 2 (HSV-2) infection were also correlated with incarceration. Conclusions. Incarcerated methamphetamine users are engaging in behaviors and being exposed to environments that put them at increased risk of infection and harmful practices. Alternatives to incarceration need to be explored for youths. PMID:18923109

Trends in methamphetamine use in young injection drug users in San Francisco from 1998 to 2004: the UFO Study.

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Inglez-Dias, Aline; Hahn, Judith A; Lum, Paula J; Evans, Jennifer; Davidson, Peter; Page-Shafer, Kimberly

2008-05-01

To describe temporal trends in methamphetamine use among young injection drug users (IDU) in San Francisco. Secondary analysis of cross-sectional baseline data collected for a longitudinal study of young IDU from 1998 to 2004. Participants were 1445 young IDU (<30 years old) who reported injection in the previous month, English-speaking, and recruited by street outreach methods. We examined trends for: lifetime (ever) and recent (30-day) methamphetamine use, including injected and non-injected, and by age group and sexual risk behaviour [men who have sex with men injecting drug users (MSM-IDU), male IDU (non-MSM) and female IDU]. In 1998, 1999, 2000, 2001, 2003 and 2004 we interviewed 237, 276, 431, 310, 147 and 44 participants, respectively. Overall, median age was 22 years [interquartile range (IQR) 20-25], 30.3% were women and median duration of injecting was 4.4 years (IQR 2-7). Prevalence of methamphetamine use was high, with 50.1% reporting recent injection, but overall there were no temporal increases in reported 'ever' injected use. Recent methamphetamine injection (past 30 days) increased significantly, and peaked at 60% in 2003. MSM-IDU had higher methamphetamine injection ever (92.3%) and recently (59.5%) compared to heterosexual male (non-MSM) IDU (81.6% and 47.3%, respectively) and to female IDU (78.4% and 46.1%, respectively). Despite reports of ubiquitous increases in methamphetamine use, there were no significant increases in 6 years in ever injecting methamphetamine overall among young IDU. MSM-IDU who reported the highest methamphetamine use overall reported some increases in recent injected use. The methamphetamine 'epidemic' was probably under way among young IDU earlier than other populations.

Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges

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Hodges, A.B; Ladenheim, B; McCoy, M.T; Beauvais, G; Cai, N; Krasnova, I.N; Cadet, J.L

2011-01-01

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dos...

Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

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Crunelle, C.L.; Veltman, D.J.; Booij, J.; van Emmerik-van Oortmerssen, K.; van den Brink, W.

2012-01-01

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence,

Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users.

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Michael E Ballard

Full Text Available Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence.Methamphetamine users and non-user controls (n = 18 per group completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride.The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008, but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622. The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010, but not methamphetamine users (r = 0.281, p = 0.258, and the group-wise interaction was significant (p = 0.030.These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.

Decline in adolescent treatment admissions for methamphetamine ...

African Journals Online (AJOL)

Background and objectives. The purpose of this report is to describe the changing trends in adolescent treatment admissions for methamphetamine in Cape Town, and to discuss possible implications. Method. Data were collected on admissions for drug abuse treatment through a regular monitoring system involving drug ...

[Dependent patient and interpersonal dependency: psychotherapeutic strategies].

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Versaevel, C

2012-04-01

This article is a review of psychotherapies for patients suffering from dependent personality and interpersonal dependency. We synthesized articles making reference to this question, notably those written by Bornstein, author who refers to the dependent personality. We highlighted the psychotherapies that have been the object of an evaluation. The research on the subject is sparse: only eight studies permitting assessment of psychotherapies in this indication in 2005. Besides these psychotherapies, we detailed other approaches which are used by practitioners in these indications. The therapy does not aim at autonomy "at all costs", but that the patient finds a dependence "adapted" to his/her environment. Before starting a therapy, an evaluation is useful to specify the type of dependence. First of all, is there a "pathological" dependence? Is the suffering of the patient secondary to his personality or not supportive enough? Does insight exist? What is the reaction of the patient if we suggest the hypothesis of a dependence on his/her part? Does he/she consider this idea or reject it? Finally, is the dependence primary or secondary? For that purpose, it is necessary to study the biography of the patient and the appearance of the comorbidity over time. The primary dependence is seen in childhood and precedes the other psychological disorders. The secondary dependence follows after the comorbidity and events of life that alter self-esteem (depression, for example). Various therapeutic strategies arise from various currents. The therapies of analytical inspiration recommend replaying the relationship of object and explicitly evoking the transfer. The behavioural and cognitive psychotherapies aim at making the patient identify the cognitions which underlie the dependence, then leading the patient to modify his/her cognition and to behave in a more autonomous way, using the theory of learning. The humanist therapies aim at a therapeutic relationship of acceptance and

Methamphetamine use among gay and bisexual men in Australia : Trends in recent and regular use from the Gay Community Periodic Surveys

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Lea, Toby; Mao, Limin; Hopwood, Max; Prestage, Garrett; Zablotska, Iryna; de Wit, John|info:eu-repo/dai/nl/06883652X; Holt, Martin

BACKGROUND: Gay and bisexual men typically report high rates of illicit drug use, including methamphetamine use. This paper aimed to analyse trends in crystal methamphetamine ('crystal') and powder methamphetamine ('speed') use among gay and bisexual men in Australia, and characterise the

Warning against co-administration of 3,4-methylenedioxymethamphetamine (MDMA) with methamphetamine from the perspective of pharmacokinetic and pharmacodynamic evaluations in rat brain.

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Yuki, Fuchigami; Rie, Ikeda; Miki, Kuzushima; Mitsuhiro, Wada; Naotaka, Kuroda; Kenichiro, Nakashima

2013-04-11

3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine often cause serious adverse effects (e.g., rhabdomyolysis, and cardiac disease) following hyperthermia triggered by release of brain monoamines such as dopamine and serotonin. Therefore, evaluation of brain monoamine concentrations is useful to predict these drugs' risks in human. This study aimed to evaluate risks of co-administration of MDMA and methamphetamine, both of which are abused frequently in Japan, based on drug distribution and monoamine level in the rat brain. Rats were allocated to three groups: (1) sole MDMA administration (12 or 25 mg/kg, intraperitoneally), (2) sole methamphetamine administration (10 mg/kg, intraperitoneally) and (3) co-administration of MDMA (12 mg/kg, intraperitoneally) and methamphetamine (10 mg/kg, intraperitoneally). We monitored pharmacokinetic and pharmacodynamic variables for drugs and monoamines in the rat brain. Area under the curve for concentration vs. time until 600 min from drug administration (AUC₀₋₆₀₀) increased from 348.0 to 689.8 μgmin/L for MDMA and from 29.9 to 243.4 μMmin for dopamine in response to co-administration of methamphetamine and MDMA compared to sole MDMA (12 mg/kg) administration. After sole methamphetamine or that with MDMA administration, AUC₀₋₆₀₀ of methamphetamine were 401.8 and 671.1 μgmin/L, and AUC₀₋₆₀₀ of dopamine were 159.9 and 243.4 μMmin. In conclusion, the brain had greater exposure to MDMA, methamphetamine and dopamine after co-administration of MDMA and methamphetamine than when these two drugs were given alone. This suggests co-administration of MDMA with methamphetamine confers greater risk than sole administration, and that adverse events of MDMA ingestion may increase when methamphetamine is co-administered. Copyright © 2013 Elsevier B.V. All rights reserved.

Methamphetamine use and correlates in two villages of the highland ethnic Karen minority in northern Thailand: a cross sectional study

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Ono-Kihara Masako

2009-05-01

Full Text Available Abstract Background The prevalence of methamphetamine use and human immunodeficiency virus (HIV incidence are high in lowland Thai society. Despite increasing social and cultural mixing among residents of highland and lowland Thai societies, however, little is known about methamphetamine use among ethnic minority villagers in the highlands. Methods A cross-sectional survey examined Karen villagers from a developed and a less-developed village on February 24 and March 26, 2003 to evaluate the prevalence and social correlates of methamphetamine use in northern Thailand. Data were collected in face-to-face interviews using a structured questionnaire. Results The response rate was 79.3% (n = 548. In all, 9.9% (males 17.6%, females 1.7% of villagers reported methamphetamine use in the previous year. Methamphetamine was used mostly by males and was significantly related to primary or lower education; to ever having worked in town; to having used opium, marijuana, or heroin in the past year; and to ever having been diagnosed with a sexually transmitted infection (STI. Conclusion Since labor migration to towns is increasingly common among ethnic minorities, the prevention of methamphetamine use and of HIV/STI infection among methamphetamine users should be prioritized to prevent HIV in this minority population in Thailand.

The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole.

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Green, A R; De Souza, R J; Williams, J L; Murray, T K; Cross, A J

1992-04-01

Studies were undertaken in mice and rats on the neurotoxic effects of methamphetamine on dopaminergic and 5-hydroxytryptaminergic neurones in the brain and the neuroprotective action of chlormethiazole. In initial studies, mice were injected with methamphetamine (5 mg/kg, i.p.) at 2 hr intervals, to a total of 4 times. This procedure produced a 66% loss of striatal dopamine and a 50% loss of tyrosine hydroxylase activity 3 days later. Chlormethiazole (50 mg/kg, i.p.), given 15 min before each dose of methamphetamine, totally prevented the methamphetamine-induced loss of tyrosine hydroxylase activity and partly prevented the loss of dopamine. Phencyclidine (20 mg/kg, i.p.), given in place of chlormethiazole, also prevented the loss of tyrosine hydroxylase. Administration to rats of 4 doses of methamphetamine (15 mg/kg, i.p.) at 3 hr intervals resulted in a 75% loss of striatal dopamine 3 days later and a similar loss of 5-HT and 5-HIAA in cortex and hippocampus. Chlormethiazole (50 mg/kg, i.p.), given 15 min before each injection of methamphetamine, protected against the loss of dopamine and indoleamine content, in the respective regions. Pentobarbital (25 mg/kg, i.p.) also provided substantial protection but diazepam (2.5 mg/kg, i.p.) was without effect. Confirming earlier studies, dizocilpine (1 mg/kg) also provided substantial protection against the methamphetamine-induced neurotoxicity. Preliminary data indicated that chlormethiazole was not neuroprotective because of a hypothermic action. These data therefore demonstrate that chlormethiazole is an effective neuroprotective agent against methamphetamine-induced neurotoxicity and extend the evidence for the possible value of this drug in preventing neurodegeneration.

Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

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Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

2015-12-01

Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence of and risk factors for methamphetamine use in northern Thai youth: results of an audio-computer-assisted self-interviewing survey with urine testing.

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Sattah, Martin V; Supawitkul, Somsak; Dondero, Timothy J; Kilmarx, Peter H; Young, Nancy L; Mastro, Timothy D; Chaikummao, Supaporn; Manopaiboon, Chomnad; Griensven, Frits van

2002-07-01

Data from drug treatment facilities, drug seizures and drug arrests suggest rapidly increasing methamphetamine use by adolescents in Thailand. However, limited quantitative data are available about the prevalence of its use or correlates of use. The purpose of our study was therefore to estimate the prevalence of methamphetamine use and to identify possible risk factors. Cross-sectional survey using anonymous audio-computer-assisted self-interview and urine specimen analysis. Chiang Rai Province, Thailand. 1725 students, 15-21 years of age (893 male and 832 female) attending one of three vocational schools in Chiang Rai Province. Three hundred and fifty male and 150 female students reported a history of having ever used methamphetamine. In addition, 128 male and 49 female students had positive urine test results, indicating recent methamphetamine use; 27 of these students denied having ever used methamphetamine. According to history, urine test, or both, 41.3% of male students and 19.0% of female students used methamphetamine. In multivariate analysis, methamphetamine use was highly correlated with the use of other substances, sexual activity, peer pressure, positive attitudes toward methamphetamine, and absence of a family confidant. Methamphetamine use is common among adolescent students in northern Thailand. Demographic, behavioral and psychosocial correlates of methamphetamine use identified in this study may be helpful for the design and implementation of preventive interventions.

A single-nucleotide polymorphism of GRIN1 in heroin and methamphetamine addicts at a rehabilitation sanatorium in Markazi province, Iran

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Ahmad Hamta

2017-03-01

Full Text Available Introduction: Using addictive drugs can change the amount of neurotransmitters, especially dopamine and glutamate. Glutamate has been known to trigger the relapse and tendency toward addictive drugs. The glutamate receptor ionotropic NMDA type subunit 1 (GRIN1 contains the single- nucleotide polymorphism C1001G (rs11146020 and encodes N-methyl-D-aspartic acid (NDMA receptor subunit 1 (NR1. The present study was conducted to investigate the relationship between the rs11146020 polymorphism in GRIN1 and addiction to heroin and methamphetamine. Methods: The present case-control study recruited 90 male heroin and methamphetamine addicts treated with methadone and 100 healthy men. Genomic DNA was extracted from peripheral blood using Iraizol kits. Four pairs of specific primers were designed using AlleleID 7.5, and the T-ARMS PCR was optimized. Results: The genotype distribution of GG, GC and CC was respectively found to be 66%, 31% and 3% in the control group and 58%, 31% and 11% in the patient group. The statistical analysis suggested no significant differences between these two groups. Conclusion: No significant relationships were observed between the C1001G polymorphism in GRIN1 and addiction to heroin and methamphetamine.

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release.

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Yun, Jaesuk

2014-05-15

Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function. Copyright © 2013 Elsevier GmbH. All rights reserved.

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.

Science.gov (United States)

Baldwin, H A; Colado, M I; Murray, T K; De Souza, R J; Green, A R

1993-03-01

1. Administration to rats of methamphetamine (15 mg kg-1, i.p.) every 2 h to a total of 4 doses resulted in a neurotoxic loss of striatal dopamine of 36% and of 5-hydroxytryptamine (5-HT) in the cortex (43%) and hippocampus (47%) 3 days later. 2. Administration of chlormethiazole (50 mg kg-1, i.p.) 15 min before each dose of methamphetamine provided complete protection against the neurotoxic loss of monoamines while administration of dizocilpine (1 mg kg-1, i.p.) using the same dose schedule provided substantial protection. 3. Measurement of dopamine release in the striatum by in vivo microdialysis revealed that methamphetamine produced an approximate 7000% increase in dopamine release after the first injection. The enhanced release response was somewhat diminished after the third injection but still around 4000% above baseline. Dizocilpine (1 mg kg-1, i.p.) did not alter this response but chlormethiazole (50 mg kg-1, i.p.) attenuated the methamphetamine-induced release by approximately 40%. 4. Dizocilpine pretreatment did not influence the decrease in the dialysate concentration of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) produced by administration of methamphetamine while chlormethiazole pretreatment decreased the dialysate concentration of these metabolites still further. 5. The concentration of dopamine in the dialysate during basal conditions increased modestly during the course of the experiment. This increase did not occur in chlormethiazole-treated rats. HVA concentrations were unaltered by chlormethiazole administration. 6. Chlormethiazole (100-1000 microM) did not alter methamphetamine (100 microM) or K+ (35 mM)-evoked release of endogenous dopamine from striatal prisms in vitro. 7. Several NMDA antagonists prevent methamphetamine-induced neurotoxicity; however chlormethiazole is not an NMDA antagonist. Inhibition of striatal dopamine function prevents methamphetamine-induced toxicity of both dopamine and 5

The impact of comorbid cannabis and methamphetamine use on mental health among regular ecstasy users.

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Scott, Laura A; Roxburgh, Amanda; Bruno, Raimondo; Matthews, Allison; Burns, Lucy

2012-09-01

Residual effects of ecstasy use induce neurotransmitter changes that make it biologically plausible that extended use of the drug may induce psychological distress. However, there has been only mixed support for this in the literature. The presence of polysubstance use is a confounding factor. The aim of this study was to investigate whether regular cannabis and/or regular methamphetamine use confers additional risk of poor mental health and high levels of psychological distress, beyond regular ecstasy use alone. Three years of data from a yearly, cross-sectional, quantitative survey of Australian regular ecstasy users was examined. Participants were divided into four groups according to whether they regularly (at least monthly) used ecstasy only (n=936), ecstasy and weekly cannabis (n=697), ecstasy and weekly methamphetamine (n=108) or ecstasy, weekly cannabis and weekly methamphetamine (n=180). Self-reported mental health problems and Kessler Psychological Distress Scale (K10) were examined. Approximately one-fifth of participants self-reported at least one mental health problem, most commonly depression and anxiety. The addition of regular cannabis and/or methamphetamine use substantially increases the likelihood of self-reported mental health problems, particularly with regard to paranoia, over regular ecstasy use alone. Regular cannabis use remained significantly associated with self reported mental health problems even when other differences between groups were accounted for. Regular cannabis and methamphetamine use was also associated with earlier initiation to ecstasy use. These findings suggest that patterns of drug use can help identify at risk groups that could benefit from targeted approaches in education and interventions. Given that early initiation to substance use was more common in those with regular cannabis and methamphetamine use and given that this group had a higher likelihood of mental health problems, work around delaying onset of initiation

Prior nicotine self-administration attenuates subsequent dopaminergic deficits of methamphetamine in rats: role of nicotinic acetylcholine receptors.

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Baladi, Michelle G; Nielsen, Shannon M; McIntosh, J Michael; Hanson, Glen R; Fleckenstein, Annette E

2016-08-01

Preclinical studies have demonstrated that oral nicotine exposure attenuates long-term dopaminergic damage induced by toxins, including repeated, high doses of methamphetamine. It is suggested that alterations in nicotinic acetylcholine receptor (nAChR) expression, including α4β2* and α6β2* subtypes, likely contribute to this protection. The current study extended these findings by investigating whether nicotine self-administration in male, Sprague-Dawley rats (a) attenuates short-term dopaminergic damage induced by methamphetamine and (b) causes alterations in levels of α4β2* and α6β2* nAChR subtypes. The findings indicate that nicotine self-administration (0.032 mg/kg/infusion for 14 days) per se did not alter α4β2* and α6β2* nAChR expression or dopamine transporter (DAT) expression and function. Interestingly, prior nicotine self-administration attenuated methamphetamine-induced decreases in DAT function when assessed 24 h, but not 1 h, after methamphetamine treatment (4×7.5 mg/kg/injection). The ability of nicotine to attenuate the effects of methamphetamine on DAT function corresponded with increases in α4β2*, but not α6β2*, nAChR binding density. Understanding the role of nAChRs in methamphetamine-induced damage has the potential to elucidate mechanisms underlying the etiology of disorders involving dopaminergic dysfunction, as well as to highlight potential new therapeutic strategies for prevention or reduction of dopaminergic neurodegeneration.

Methamphetamine use and sexual risk behaviour in Cape Town ...

African Journals Online (AJOL)

4Department of Psychiatry & Mental Health, University of Cape Town, South Africa. Abstract. Objective: ... Keywords: Methamphetamine; Sexual behaviour; HIV; South Africa ... to high school students who had used drugs other than MA in their.

Effects of length of abstinence on decision-making and craving in methamphetamine abusers.

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Guibin Wang

Full Text Available RATIONALE: The majority of drug abusers are incapable of sustaining abstinence over any length of time. Accumulating evidence has linked intense and involuntary craving, Impulsive decision-making and mood disturbances to risk for relapse. However, little is known about temporal changes of these neuropsychological functions in methamphetamine (METH-dependent individuals. OBJECTIVES: To investigate the effect of length of abstinence on decision-making, craving (baseline and cue-induced, and emotional state in METH-addicted individuals. METHODS: In this cross-sectional study, 183 adult METH-dependent patients at an addiction rehabilitation center who were abstinent for 6 days (n = 37, 14 days (n = 33, 1 month (n = 31, 3 months (n = 30, 6 months (n = 26, or 1 year (n = 30 and 39 healthy subjects were administered the Iowa Gambling Task (IGT to assess decision-making performance. Depression, anxiety, and impulsivity were also examined. One hundred thirty-nine METH abusers who were abstinent for the aforementioned times then underwent a cue session, and subjective and physiological measures were assessed. RESULTS: METH dependent individuals who were abstinent for longer periods of time exhibited better decision-making than those who were abstinent for shorter periods of time. And self-reported emotional symptoms improved with abstinence. METH abusers' ratings of craving decreased with the duration of abstinence, while cue-induced craving increased until 3 months of abstinence and decreased at 6 months and 1 year of abstinence. CONCLUSIONS: We present time-dependent alterations in decision-making, emotional state, and the incubation of cue-induced craving in METH-dependent individuals, which might have significant clinical implications for the prevention of relapse.

Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non-Indigenous people who inject drugs.

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Smirnov, Andrew; Kemp, Robert; Ward, James; Henderson, Suzanna; Williams, Sidney; Dev, Abhilash; Najman, Jake M

2016-09-01

Despite over-representation of Indigenous Australians in sentinel studies of injecting drug use, little is known about relevant patterns of drug use and dependence. This study compares drug dependence and possible contributing factors in Indigenous and non-Indigenous Australians who inject drugs. Respondent-driven sampling was used in major cities and 'peer recruitment' in regional towns of Queensland to obtain a community sample of Indigenous (n = 282) and non-Indigenous (n = 267) injectors. Data are cross sectional. Multinomial models were developed for each group to examine types of dependence on injected drugs (no dependence, methamphetamine-dependent only, opioid-dependent only, dependent on methamphetamine and opioids). Around one-fifth of Indigenous and non-Indigenous injectors were dependent on both methamphetamine and opioids in the previous 12 months. Psychological distress was associated with dual dependence on these drugs for Indigenous [adjusted relative risk (ARR) 4.86, 95% confidence interval (CI) 2.08-11.34] and non-Indigenous (ARR 4.14, 95% CI 1.59-10.78) participants. Unemployment (ARR 8.98, 95% CI 2.25-35.82) and repeated (> once) incarceration as an adult (ARR 3.78, 95% CI 1.43-9.97) were associated with dual dependence for Indigenous participants only. Indigenous participants had high rates of alcohol dependence, except for those dependent on opioids only. The drug dependence patterns of Indigenous and non-Indigenous people who inject drugs were similar, including the proportions dependent on both methamphetamine and opioids. However, for Indigenous injectors, there was a stronger association between drug dependence and contextual factors such as unemployment and incarceration. Expansion of treatment options and community-level programs may be required. [Smirnov A, Kemp R, Ward J, Henderson S, Williams S, Dev A, Najman J M. Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non-Indigenous people who

Alcohol, Methamphetamine, and Marijuana Exposure Have Distinct Effects on the Human Placenta.

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Carter, R Colin; Wainwright, Helen; Molteno, Christopher D; Georgieff, Michael K; Dodge, Neil C; Warton, Fleur; Meintjes, Ernesta M; Jacobson, Joseph L; Jacobson, Sandra W

2016-04-01

Animal studies have demonstrated adverse effects of prenatal alcohol exposure on placental development, but few studies have examined these effects in humans. Little is known about effects of prenatal exposure to methamphetamine, marijuana, and cigarette smoking on placental development. Placentas were collected from 103 Cape Coloured (mixed ancestry) pregnant women recruited at their first antenatal clinic visit in Cape Town, South Africa. Sixty-six heavy drinkers and 37 nondrinkers were interviewed about their alcohol, cigarette smoking, and drug use at 3 antenatal visits. A senior pathologist, blinded to exposure status, performed comprehensive pathology examinations on each placenta using a standardized protocol. In multivariable regression models, effects of prenatal exposure were examined on placental size, structure, and presence of infections and meconium. Drinkers reported a binge pattern of heavy drinking, averaging 8.0 drinks/occasion across pregnancy on 1.4 d/wk. 79.6% smoked cigarettes; 22.3% used marijuana; and 17.5% used methamphetamine. Alcohol exposure was related to decreased placental weight and a smaller placenta-to-birthweight ratio. By contrast, methamphetamine was associated with larger placental weight and a larger placenta-to-birthweight ratio. Marijuana was also associated with larger placental weight. Alcohol exposure was associated with increased risk of placental hemorrhage. Prenatal alcohol, drug, and cigarette use were not associated with chorioamnionitis, villitis, deciduitis, or maternal vascular underperfusion. Alcohol and cigarette smoking were associated with a decreased risk of intrauterine passing of meconium, a sign of acute fetal stress and/or hypoxia; methamphetamine, with an increased risk. This is the first human study to show that alcohol, methamphetamine, and marijuana were associated with distinct patterns of pathology, suggesting different mechanisms mediating their effects on placental development. Given the growing

Methamphetamine Use among Rural White and Native American Adolescents: An Application of the Stress Process Model

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Eitle, David J.; Eitle, Tamela McNulty

2013-01-01

Methamphetamine use has been identified as having significant adverse health consequences, yet we know little about the correlates of its use. Additionally, research has found that Native Americans are at the highest risk for methamphetamine use. Our exploratory study, informed by the stress process model, examines stress and stress buffering…

Gut Microbiota Analysis in Rats with Methamphetamine-Induced Conditioned Place Preference

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Tingting Ning

2017-08-01

Full Text Available Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP were analyzed through 16S rRNA gene sequencing. The fecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the fecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

Imagery Scripts and a Computerized Subtraction Stress Task Both Induce Stress in Methamphetamine Users: A Controlled Laboratory Study

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Kathleen J. Garrison

2010-01-01

Full Text Available Patients treated for methamphetamine (MA dependence have a high rate of relapse, and stress is thought to play a key role. We sought to develop a computerized procedure for experimentally inducing stress in MA users. In a within-subjects design, we compared a computerized subtraction stress task (SST to personalized stress-imagery scripts and a control condition (neutral imagery in 9 former MA users, recruited in San Francisco in 2006–2007. We assessed blood hormone levels, anxiety and craving for MA on visual analog scales, and the Positive and Negative Affect Schedule and made linear mixed-effects models to analyze the results. Both the SST and stress scripts were effective in inducing self-report markers of stress in MA users. Because the SST is easily reproducible and requires less time of staff and participants, it may be a useful alternative for measuring stress reactivity in drug users.

Methamphetamine and dopamine neurotoxicity: differential effects of agents interfering with glutamatergic transmission.

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Boireau, A; Bordier, F; Dubédat, P; Doble, A

1995-07-28

The effects of riluzole and lamotrigine, two agents which interfere with the release of glutamate (GLU), and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of methamphetamine-induced depletion of dopamine (DA) levels in mice. Repeated injections with methamphetamine (4 x 5 mg/kg i.p.) markedly decreased levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. When mice were treated with riluzole (2 x 10 mg/kg p.o.), no protection was observed against the decrease in DA and the two metabolites. Lamotrigine (2 x 10 mg/kg p.o.) was also inactive. Treatment with MK-801 (2 x 2.5 mg/kg i.p.) antagonized the decrease in DA, DOPAC and HVA levels induced by the neurotoxin. Thus, unlike an NMDA blocker, drugs that interfere with GLU release did not antagonize the methamphetamine-induced DA neurotoxicity in mice. The consequences of this inactivity are discussed in terms of the reliability of this model to test new drugs with putative efficacy in the treatment of Parkinson's disease.

Sex differences in disinhibition and its relationship to physical abuse in a sample of stimulant-dependent patients.

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Winhusen, Theresa; Lewis, Daniel

2013-04-01

Research suggests that impulsivity is a vulnerability factor for developing stimulant dependence, that women develop dependence more quickly than men, and that physical abuse can increase impulsivity and may have greater adverse health consequences in women. This study sought to tie these findings together by evaluating: (1) sex differences in disinhibition prior to lifetime initiation of stimulant abuse and (2) the relationship between physical abuse and disinhibition in stimulant-dependent patients. The Frontal Systems Behavior Scale (FrSBe) is a reliable and valid self-report assessment of three neurobehavioral domains associated with frontal systems functioning (Apathy, Disinhibition, and Executive Dysfunction, summed for a Total), that assesses pre-morbid functioning and has a specific cutoff for defining clinically significant abnormalities. Six sites evaluating 12-step facilitation for stimulant abusers obtained the FrSBe from 118 methamphetamine- and/or cocaine-dependent participants. Lifetime physical abuse was measured by the Addiction Severity Index (ASI). The proportion reporting clinically significant disinhibition was significantly higher in women (64.9%) than in men (45.0%, p=0.04), with no significant difference on the other FrSBe scales. Physical abuse in women, but not men, was associated with worse functioning, with physically abused, relative to non-abused, women having a significantly greater proportion with clinically significant disinhibition (pabuse and that physical abuse in women is associated with greater disinhibition. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

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Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Francescutti, Dina M; Sykes, Catherine E; Shah, Mrudang M; Thomas, David M; Kuhn, Donald M

2013-04-01

Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity. © 2012 International Society for Neurochemistry.

Changes in psychiatric symptoms among persons with methamphetamine dependence predicts changes in severity of drug problems but not frequency of use.

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Polcin, Douglas L; Korcha, Rachael; Bond, Jason; Galloway, Gantt; Nayak, Madhabika

2016-01-01

Few studies have examined how changes in psychiatric symptoms over time are associated with changes in drug use and severity of drug problems. No studies have examined these relationships among methamphetamine (MA)-dependent persons receiving motivational interviewing within the context of standard outpatient treatment. Two hundred seventeen individuals with MA dependence were randomly assigned to a standard single session of motivational interviewing (MI) or an intensive 9-session model of MI. Both groups received standard outpatient group treatment. The Addiction Severity Index (ASI) and timeline follow-back (TLFB) for MA use were administered at treatment entry and 2-, 4-, and 6-month follow-ups. Changes in ASI psychiatric severity between baseline and 2 months predicted changes in ASI drug severity during the same time period, but not changes on measures of MA use. Item analysis of the ASI drug scale showed that psychiatric severity predicted how troubled or bothered participants were by their drug us, how important they felt it was for them to get treatment, and the number of days they experienced drug problems. However, it did not predict the number days they used drugs in the past 30 days. These associations did not differ between study conditions, and they persisted when psychiatric severity and outcomes were compared across 4- and 6-month time periods. Results are among the first to track how changes in psychiatric severity over time are associated with changes in MA use and severity of drug problems. Treatment efforts targeting reduction of psychiatric symptoms among MA-dependent persons might be helpful in reducing the level of distress and problems associated with MA use but not how often it is used. There is a need for additional research describing the circumstances under which the experiences and perceptions of drug-related problems diverge from frequency of consumption.

Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

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Giardino, William J; Mark, Gregory P; Stenzel-Poore, Mary P; Ryabinin, Andrey E

2012-02-01

Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5-10 mg/kg). While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction.

Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

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Banks, Matthew L

2016-08-01

Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

Gender and Sex Trading Among Active Methamphetamine Users in Cape Town, South Africa.

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Lion, Ryan R; Watt, Melissa H; Wechsberg, Wendee M; Meade, Christina S

2017-05-12

South Africa has experienced a tremendous rise in methamphetamine use since the year 2000. Sex trading is a global phenomenon that has been observed in active drug users and has been associated with risks for HIV infection and violence. This paper describes and examines the correlates of sex trading among active methamphetamine users in Cape Town, South Africa. Through peer referral, 360 (201 male; 159 female) active methamphetamine users were recruited in a peri-urban township. Demographics, sex trading, drug use, trauma, and mental health were assessed by a structured clinical interview and computer survey. Logistic regression models were used to examine predictors of sex trading for men and women. In the past 3 months, 40% of men and 33% of women endorsed trading sex for methamphetamine or money. Among these, they reported trading with same sex partners (33%), high rates of inconsistent condom use (73%), and incidences of physical (23%) and sexual (27%) assault when sex trading. Increased drug use severity was correlated with sex trading. Women with experiences of violence and trauma were also more likely to trade sex. Conclusions/importance: The results stress a need for linkage to drug treatment, as addiction may be fueling sex trading. Targeted interventions geared towards safe sex practices may reduce risky sexual behaviors. Women need interventions that are attuned to their specific vulnerabilities. More research is needed to explore the experiences of men who have sex with men given their particularly high rates of sex trading behavior.

Chronic variable stress and intravenous methamphetamine self-administration – role of individual differences in behavioral and physiological reactivity to novelty

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Taylor, S.B.; Watterson, L.R.; Kufahl, P.R.; Nemirovsky, N.E.; Tomek, S.E.; Conrad, C.D.; Olive, M.F.

2016-01-01

Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. PMID:27163191

The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

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Susana T Valente

2015-10-01

Full Text Available Antiretroviral therapy (ART has dramatically improved the lives of HIV-1 infected individuals. Nonetheless, HIV associated neurocognitive disorders (HAND, which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life.The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat in the brain. Tat is a secreted viral protein that crosses the blood brain barrier into the central nervous system, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine abusers is high among the HIV-1-positive population compared to the general population. On the other hand, methamphetamine abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and methamphetamine use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and methamphetamine in HAND and discuss a few promising potential therapeutic developments.

Evaluating methamphetamine use and risks of injection initiation among street youth: the ARYS study

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Montaner Julio SG

2006-05-01

Full Text Available Abstract Many Canadian cities are experiencing ongoing infectious disease and overdose epidemics among injection drug users (IDU. These health concerns have recently been exacerbated by the increasing availability and use of methamphetamine. The challenges of reducing health-related harms among IDU have led to an increased recognition that strategies to prevent initiation into injection drug use must receive renewed focus. In an effort to better explore the factors that may protect against or facilitate entry into injection drug use, the At Risk Youth Study (ARYS has recently been initiated in Vancouver, Canada. The local setting is unique due to the significant infrastructure that has been put in place to reduce HIV transmission among active IDU. The ARYS study will seek to examine the impact of these programs, if any, on non-injection drug users. In addition, Vancouver has been the site of widespread use of methamphetamine in general and has seen a substantial increase in the use of crystal methamphetamine among street youth. Hence, the ARYS cohort is well positioned to examine the harms associated with methamphetamine use, including its potential role in facilitating initiation into injection drug use. This paper provides some background on the epidemiology of illicit drug use among street youth in North America and outlines the methodology of ARYS, a prospective cohort study of street youth in Vancouver, Canada.

Context-dependent effects of a single administration of mirtazapine on the expression of methamphetamine-induced conditioned place preference

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Robin eVoigt

2012-01-01

Full Text Available Re-exposure to cues repeatedly associated with methamphetamine (Meth can trigger Meth-seeking and relapse in the abstinent abuser. Weakening the conditioned Meth-associated memory during cue re-exposure may provide a means for relapse-reduction pharmacotherapy. Accordingly, we sought to determine if the atypical antidepressant mirtazapine disrupted the long-term maintenance of Meth-induced conditioned place preference (CPP when administered in conjunction with re-exposure to contextual conditioning cues, and if this effect was altered by Meth being present during cue re-exposure. First, we evaluated the effect of mirtazapine on the maintenance of Meth-induced CPP during re-exposure to either the saline- or Meth-paired chamber 12 days after conditioning. Meth conditioned rats subsequently administered mirtazapine expressed CPP independent of re-exposure to the saline- or Meth-paired chamber; but the magnitude of CPP was significantly less for mirtazapine-treated rats re-exposed to the Meth-paired chamber. Next, we evaluated the effect of mirtazapine on a ‘reinforced re-exposure’ to the Meth-paired context. Administration of mirtazapine vehicle and Meth, prior to re-exposure to the Meth-paired chamber did not disrupt the ability of rats to demonstrate CPP on day 20; however, rats administered mirtazapine and Meth prior to re-exposure to the Meth-paired chamber did not demonstrate CPP. These results indicate a context-dependent effect of mirtazapine, and that the ability of mirtazapine to disrupt the long-term maintenance of CPP is greatest when the atypical antidepressant is tested with a combination of Meth injection and contextual cues.

Effects of L-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys.

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Kohut, Stephen J; Bergman, Jack; Blough, Bruce E

2016-03-01

Monoamine releasers with prominent dopaminergic actions, e.g., D-methamphetamine (D-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, D-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. The L-isomer of methamphetamine (L-MA), unlike D-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether L-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Separate groups (N = 4-5) of rhesus monkeys were studied to determine whether L-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. L-MA, like D-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10-day treatments with continuously infused L-MA (0.032-0.32 mg/kg/h, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. These results indicate that L-MA both shares discriminative stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. L-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder.

Dependency in Critically Ill Patients

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Rumei Yang

2016-03-01

Full Text Available By necessity, critically ill patients admitted to intensive care units (ICUs have a high level of dependency, which is linked to a variety of negative feelings, such as powerlessness. However, the term dependency is not well defined in the critically ill patients. The concept of “dependency” in critically ill patients was analyzed using a meta-synthesis approach. An inductive process described by Deborah Finfgeld-Connett was used to analyze the data. Overarching themes emerged that reflected critically ill patients’ experience and meaning of being in dependency were (a antecedents: dependency in critically ill patients was a powerless and vulnerable state, triggered by a life-threatening crisis; (b attributes: the characteristic of losing “self” was featured by dehumanization and disembodiment, which can be alleviated by a “self”-restoring process; and (c outcomes: living with dependency and coping with dependency. The conceptual model explicated here may provide a framework for understanding dependency in critically ill patients.

Ibudilast may improve attention during early abstinence from methamphetamine.

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Birath, J Brandon; Briones, Marisa; Amaya, Stephanie; Shoptaw, Steven; Swanson, Aimee-Noelle; Tsuang, John; Furst, Benjamin; Heinzerling, Keith; Obermeit, Lisa; Maes, Lauryn; McKay, Charles; Wright, Matthew J

2017-09-01

Inattention is a deficit related to instilling abstinence from methamphetamine (MA) dependence. This study aimed to determine whether ibudilast (IB; 50mg bid) improves attentional abilities compared to placebo during early abstinence from MA dependence. Attention was assessed in 11 MA-dependent non-treatment seeking participants in a phase IB safety-interaction trial. The Conners' Continuous Performance Test-II (CPT-II), a measure of sustained attention and response inhibition, was administered at baseline and on day 22, 48h post a MA challenge under placebo (P; n=6) or IB 50mg bid (n=5). Group differences were compared using Mann-Whitney U Tests. Groups were similar at baseline in premorbid intellectual functioning, attention deficit hyperactivity symptom scores, impulsivity ratings, and education level, but differed in age. Demographically corrected T-scores for CPT-II performances were utilized. Although no group differences in sustained attention existed at baseline, at follow-up, the IB group (Mdn=44.4) showed reduced variability in response times compared with the P group (Mdn=69.9), U=0.00, z=-2.74, p=.006, r=.83. The IB group (Mdn=45.8) also gave fewer perseverative responses than the P group (Mdn=67.0), U=2.00, z=-2.50, p=.01, r=.75. No other significant differences were observed. Findings suggest that IB may have a protective effect on sustained attention during early abstinence from MA dependence. This may guide thinking about mechanism of action should IB demonstrate efficacy as a treatment for MA dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

Remediation of Manufactured Methamphetamine in Clandestine Laboratories. A Literature Review

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The purpose of the current literature review was to identify, collect, review, and organize all available information concerning the remediation of methamphetamine found in clandestine laboratories through an analysis of routinely collected data sources. There were numerous peer ...

“Evaluation of a peer network intervention trial among young methamphetamine users in Chiang Mai, Thailand”

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Sutcliffe, Catherine; Srirojn, Bangorn; Latkin, Carl A; Aramratanna, Ajpinun; Sherman, Susan G

2009-01-01

Since the 1990s, there has been a proliferation of methamphetamine use in Thailand, particularly among young people. Simultaneously, risky sexual behaviors among this population have increased. This study examined the effects of a peer network intervention and a life skills intervention on methamphetamine and HIV risk behaviors among 18–25 year olds in Chiang Mai, Thailand. Between April 2005 and June 2007, we conducted a randomized behavioral trial to compare the efficacy of a peer educator, network-oriented intervention with a best practice, life-skills curriculum on methamphetamine use, sexual behaviors, and incident sexually transmitted infections (STIs). Follow-up occurred at three, six, nine, and twelve months. Both conditions consisted of seven, two hour, small group sessions. Longitudinal analyses of the three outcomes were conducted by fitting repeated measures logistic regression models using generalized estimating equations. Participants (N=983) attended a median of six sessions, with no differences between arms. At each follow-up visit, retention was greater than 85%. Participants were 75% male and were a median of 19 years old. Over time, participants in both conditions showed a significant and dramatic decline in self-reported methamphetamine use (99% at baseline versus 53% at 12-months, p<0.0001) and significant increase in consistent condom use (32% baseline versus 44% at 12 months, p<0.0001). Incident STIs were common, with no differences between arms. Chlamydia had the highest incidence rate, 9.85/100 person-years and HIV had a low incidence rate of 0.71/100 person-years. Among young Thais, we found that a peer educator, network-oriented intervention was associated with reductions in methamphetamine use, increases in condom use, and reductions in incident STIs over 12 months. We also found parallel reductions with the life skills condition. To our knowledge, this is the first such trial targeting this population. Small group interventions are an

Methamphetamine use and sexual risk behaviour in Cape Town ...

African Journals Online (AJOL)

Objective: Community studies and studies of admissions to drug treatment centers indicate a dramatic increase in the prevalence of methamphetamine use in Cape Town since 2003. There has also been a substantial increase over this time period in the prevalence of HIV infection among women attending public antenatal ...

Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors

Science.gov (United States)

Nader, Joëlle; Rapino, Cinzia; Gennequin, Benjamin; Chavant, Francois; Francheteau, Maureen; Makriyannis, Alexandros; Duranti, Andrea; Maccarrone, Mauro; Solinas, Marcello; Thiriet, Nathalie

2016-01-01

Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed to increase their endogenous tone. In this study, we evaluated whether ECS stimulation could reduce the neurotoxicity of high doses of methamphetamine on the dopamine system. We found that methamphetamine alters the levels of the major endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in the striatum, suggesting that the ECS participates in the brain responses to methamphetamine. Δ9-tetrahydrocannabinol (THC), a cannabis-derived agonist of both CB1 and CB2 cannabinoid receptors, or inhibitors of the main enzymes responsible for the degradation of AEA and 2-AG (URB597 and JZL184, respectively), blunted the decrease in striatal protein levels of tyrosine hydroxylase induced by methamphetamine. In addition, antagonists of CB2, but not of CB1, blocked the preventive effects of URB597 and JZL184, suggesting that only the former receptor subtype is engaged in neuroprotection exerted by ECS stimulation. Finally, we found that methamphetamine increases striatal levels of the cytokine tumor necrosis factor alpha, an effect that was blocked by ECS stimulation. Altogether, our results indicate that stimulation of ECS prior to the administration of an overdose of meth-amphetamine considerably reduces the neurotoxicity of the drug through CB2 receptor activation and highlight a protective function for the ECS against the toxicity induced by drugs and other external insults to the brain. This article is part of the Special Issue entitled ‘CNS Stimulants’. PMID:24709540

A rapid novel derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography electron ionization and chemical ionization mass spectrometric analysis.

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Dasgupta, A; Spies, J

1998-05-01

Amphetamine and methamphetamine are commonly abused central nervous system stimulants. We describe a rapid new derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography-mass spectrometric analysis. Amphetamine and methamphetamine, along with N-propyl amphetamine (internal standard), were extracted from urine using 1-chlorobutane. The derivatization with 2,2,2-trichloroethyl chloroformate can be achieved at room temperature in 10 minutes. The electron ionization mass spectrum of amphetamine 2,2,2-trichloroethyl carbamate showed two weak molecular ions at m/z 309 and 311, but showed diagnostic strong peaks at m/z 218, 220, and 222. In contrast, chemical ionization of the mass spectrum of amphetamine 2,2,2-trichloroethyl carbamate showed strong (M + 1) ions at m/z 310 and 312 and other strong diagnostic peaks at m/z 274 and 276. The major advantages of this derivative are the presence of a diagnostic cluster of peaks due to the isotopic effect of three chlorine atoms (isotopes 35 and 37) in the derivatized molecule and the relative ease of its preparation. We also observed strong molecular ions for derivatized methamphetamine in the chemical ionization mass spectrum, but the molecular ions were very weak in the electron ionization mass spectrum. We used the scan mode of mass spectrometry in all analyses. When using a urine standard containing 1,000 ng/mL of amphetamine (a 7.4-micromol/L concentration) and methamphetamine (a 6.7-micromol/L concentration), the within-run precisions were 4.8% for amphetamine and 3.6% for methamphetamine. The corresponding between-run precisions were 5.3% for amphetamine and 6.7% for methamphetamine. The assay was linear for amphetamine and methamphetamine concentrations of 250 to 5,000 ng/mL (amphetamine, 1.9-37.0 micromol/L; methamphetamine, 1.7-33.6 micromol/L). The detection limit was 100 ng/mL (amphetamine, 0.74 micromol/L; methamphetamine, 0.67 micromol/L) using the scan mode

Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized Texting for Adherence Building for Antiretroviral Adherence and Substance Use Assessment among HIV-Infected Methamphetamine Users

Directory of Open Access Journals (Sweden)

David J. Moore

2013-01-01

Full Text Available The feasibility, use, and acceptability of text messages to track methamphetamine use and promote antiretroviral treatment (ART adherence among HIV-infected methamphetamine users was examined. From an ongoing randomized controlled trial, 30-day text response rates of participants assigned to the intervention (individualized texting for adherence building (iTAB, n = 20 were compared to those in the active comparison condition (n = 9. Both groups received daily texts assessing methamphetamine use, and the iTAB group additionally received personalized daily ART adherence reminder texts. Response rate for methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of the time. Text-derived methamphetamine use data was correlated with data from a structured substance use interview covering the same time period (P<0.05. The iTAB group responded to 69.0% of adherence reminder texts; among those responses, 81.8% endorsed taking ART medication. Standardized feedback questionnaire responses indicated little difficulty with the texts, satisfaction with the study, and beliefs that future text-based interventions would be helpful. Moreover, most participants believed the intervention reduced methamphetamine use and improved adherence. Qualitative feedback regarding the intervention was positive. Future studies will refine and improve iTAB for optimal acceptability and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277.

Methamphetamine compromises gap junctional communication in astrocytes and neurons.

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Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A

2016-05-01

Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher

The meth brain: methamphetamines alter brain functions via NMDA receptors

Czech Academy of Sciences Publication Activity Database

Proft, Juliane; Weiss, Norbert

2015-01-01

Roč. 34, č. 1 (2015), s. 1-3 ISSN 0231-5882 R&D Projects: GA ČR GA15-13556S Institutional support: RVO:61388963 Keywords : ion channel * methamphetamine * piriform cortex * NMDA receptor * AMPA receptor Subject RIV: CE - Biochemistry Impact factor: 0.892, year: 2015

Reducing widespread pipe sharing and risky sex among crystal methamphetamine smokers in Toronto: do safer smoking kits have a potential role to play?

Directory of Open Access Journals (Sweden)

Hunter Charlotte

2012-02-01

Full Text Available Abstract Background Crystal methamphetamine smoking is associated with many negative health consequences, including the potential for transmission of hepatitis. We examined whether or not a kit for crystal methamphetamine smoking might have some potential to reduce the negative health effects of crystal methamphetamine smoking. Methods Five focus groups were conducted with crystal methamphetamine smokers recruited by community health agencies and youth shelters in Toronto, Canada. Target groups included homeless/street-involved youth, sex workers, men who have sex with men, and youth in the party scene. Participants (n = 32 were asked questions about motivations for crystal methamphetamine use, the process of smoking, health problems experienced, sharing behaviour, risky sexual practices, and the ideal contents of a harm reduction kit. Results Pipe sharing was widespread among participants and was deemed integral to the social experience of smoking crystal methamphetamine. Heated pipes were unlikely to cause direct injuries, but participants mentioned having dry, cracked lips, which may be a vector for disease transmission. Many reported having sex with multiple partners and being less likely to use condoms while on the drug. Demand for harm reduction kits was mixed. Conclusions Changing pipe sharing behaviours may be difficult because many participants considered sharing to be integral to the social experience of smoking crystal methamphetamine. Within the context of a broader health promotion and prevention program, pilot testing of safer smoking kits to initiate discussion and education on the risks associated with sharing pipes and unprotected sex for some communities (e.g., homeless/street-involved youth is worth pursuing.

Development of a dual test procedure for DNA typing and methamphetamine detection using a trace amount of stimulant-containing blood.

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Irii, Toshiaki; Maebashi, Kyoko; Fukui, Kenji; Sohma, Ryoko; Matsumoto, Sari; Takasu, Shojiro; Iwadate, Kimiharu

2016-05-01

Investigation of drug-related crimes, such as violation of the Stimulant Drug Control Law, requires identifying the used drug (mainly stimulant drugs, methamphetamine hydrochloride) from a drug solution and the DNA type of the drug user from a trace of blood left in the syringe used to inject the drug. In current standard test procedures, DNA typing and methamphetamine detection are performed as independent tests that use two separate portions of a precious sample. The sample can be entirely used up by either analysis. Therefore, we developed a new procedure involving partial lysis of a stimulant-containing blood sample followed by separation of the lysate into a precipitate for DNA typing and a liquid-phase fraction for methamphetamine detection. The method enables these two tests to be run in parallel using a single portion of sample. Samples were prepared by adding methamphetamine hydrochloride water solution to blood. Samples were lysed with Proteinase K in PBS at 56°C for 20min, cooled at -20°C after adding methanol, and then centrifuged at 15,000rpm. Based on the biopolymer-precipitating ability of alcohol, the precipitate was used for DNA typing and the liquid-phase fraction for methamphetamine detection. For DNA typing, the precipitate was dissolved and DNA was extracted, quantified, and subjected to STR analysis using the AmpFℓSTR® Identifiler® Plus PCR Amplification Kit. For methamphetamine detection, the liquid-phase fraction was evaporated with N2 gas after adding 20μL acetic acid and passed through an extraction column; the substances captured in the column were eluted with a solvent, derivatized, and quantitatively detected using gas chromatograph/mass spectrometry. This method was simple and could be completed in approximately 2h. Both DNA typing and methamphetamine detection were possible, which suggests that this method may be valuable for use in criminal investigations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sex differences in social interaction of methamphetamine-treated rats

Czech Academy of Sciences Publication Activity Database

Šlamberová, R.; Mikulecká, Anna; Pometlová, M.; Schutová, B.; Hrubá, L.; Deykun, K.

2011-01-01

Roč. 22, č. 7 (2011), s. 617-623 ISSN 0955-8810 R&D Projects: GA MŠk(CZ) 1M0517 Grant - others:GA ČR(CZ) GAP303/10/0580 Institutional research plan: CEZ:AV0Z50110509 Keywords : estrogen * methamphetamine * rat * sex difference * social behavior * testosterone Subject RIV: FH - Neurology Impact factor: 2.720, year: 2011

Dental Disease Prevalence among Methamphetamine and Poly-drug Users in an Urban Setting: A Pilot Study

Science.gov (United States)

Brown, Carolyn; Krishnan, Sumathi; Hursh, Kevin; Yu, Michelle; Johnson, Paul; Page, Kimberly; Shiboski, Caroline H.

2013-01-01

Background/Objectives Rampant tooth decay has been reported among methamphetamine users. We investigated the prevalence of dental disease and associated risk behaviors in methamphetamine users compared to heroin users. Methods This pilot project is a cross-sectional study of an on-going cohort of young adult injection-drug users (IDUs) in San Francisco. An oral health questionnaire was administered by a research-assistant, and two dentists performed clinical examinations to record the Decayed-Missing-Filled-Surfaces (DMFS) index, presence of residual roots, the Simplified Oral Hygiene Index, and salivary hypofunction. Results The prevalence of dental disease among 58 young adult IDUs was strikingly high compared to the U.S. general population, however, there was no difference in the level of dental disease between the methamphetamine and heroin users in this study. The mean DMFS and number of decayed surfaces exceeded 28 in both groups. Conclusions While no difference in dental disease between methamphetamine and heroin users was detected, we found a high prevalence of caries and caries-associated behaviors in this sample of young adult IDUs. Clinical Implications Given the high level of dental disease observed in this population of young adult IDUs, one next step may be to explore the feasibility and effectiveness of providing low-intensity preventative measures (e.g., distribution of chlorhexidine rinses, xylitol gum, application of fluoride varnishes) through outreach workers. PMID:22942146

Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats.

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Ganapati, Shweta; Grabitz, Stephanie D; Murkli, Steven; Scheffenbichler, Flora; Rudolph, Maíra I; Zavalij, Peter Y; Eikermann, Matthias; Isaacs, Lyle

2017-08-17

We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-β-CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods ( 1 H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (K a values) spanning from 10 8  m -1 . We also report X-ray crystal structures of CB[7]⋅methamphetamine and 1⋅methamphetamine. We found that 2, but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine. The bioavailability of the calabadions and their convergent building block synthesis suggest potential for further structural optimization as reversal agents for intoxication with nonopioid drugs of abuse for which no treatments are currently available. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distinct effects of methamphetamine on autophagy–lysosome and ubiquitin–proteasome systems in HL-1 cultured mouse atrial cardiomyocytes

International Nuclear Information System (INIS)

Funakoshi-Hirose, Izumi; Aki, Toshihiko; Unuma, Kana; Funakoshi, Takeshi; Noritake, Kanako; Uemura, Koichi

2013-01-01

Highlights: • The psychostimulant drug methamphetamine is also known to cause cardiovascular injuries. • Methamphetamine cardiotoxicity was examined using HL-1 mouse atrial cardiomyocytes. • Methamphetamine impairs the autophagy–lysosome protein degradation system. • Methamphetamine causes myosin heavy chain degradation by the ubiquitin–proteasome system. - Abstract: The aim of this study is to investigate the molecular mechanism underling the cardiotoxicity of methamphetamine, a psychostimulant drug that is currently abused in the world. A mouse atrial cardiac cell line, HL-1, which retains phenotypes of cardiac cells and serves as a useful model for examining cardiac pathophysiology, was used for this purpose. During treatment with 1 mM methamphetamine (MAP) for 3–48 h, massive but transient cytoplasmic vacuolization (3–12 h) followed by an intracellular accumulation of granules (24–48 h) was observed under light microscopy. The vacuoles were surrounded by the lysosome membrane marker LAMP1, while the granules colocalized with the autophagy markers LC3 and p62 as well as ubiquitinated proteins. Western blot analysis showed that LC3 was activated during MAP administration, although p62 was not degraded but rather accumulated. Concordant with p62 accumulation, the nuclear translocation of an anti-oxidative transcription factor, Nrf2, and the subsequent induction of its target gene, HO-1, was observed, suggesting an impairment of autophagic protein degradation and the subsequent activation of the p62/Nrf2/HO-1 pathway. In addition, proteomic analysis revealed a reduction in myosin heavy chain (MHC) protein levels during MAP administration. The ubiquitination of MHC and the induction of the muscle sarcomere protein-specific E3 ubiquitin ligases MuRF1 and atrogin-1 were proved by immunoprecipitation and quantitative real-time PCR, respectively. Taken together, the vacuolization of lysosomes and the subsequent accumulation of autophagosomes indicate

Adult Patients' Experiences of Nursing Care Dependence.

Science.gov (United States)

Piredda, Michela; Matarese, Maria; Mastroianni, Chiara; D'Angelo, Daniela; Hammer, Marilyn J; De Marinis, Maria Grazia

2015-09-01

Care dependence can be associated with suffering and humiliation. Nurses' awareness of patients' perception of care dependence is crucial to enable them in helping the dependent persons. This study aimed to describe adult patients' experience of nursing care dependence. A metasynthesis was conducted to integrate qualitative findings from 18 studies published through December 2014 on adult patients' experiences of care dependency. Procedures included the Johanna Briggs Institute approach for data extraction, quality appraisal, and integration of findings. The experience of dependence revealed the concept of the embodied person, particularly in relation to care of the physical body. The relationship between the individual and nurses within the context of care had a major impact for dependent patients. When the care relation was perceived as positive, the experience led to the development of the person in finding new balances in life, but when it was perceived as negative, it increased patient' suffering. Care dependence is manifested mostly as bodily dependence and is consistent with its relational nature. The nurse-patient relationship is important to the dependent patients' experience. A greater understanding of patients' experiences of dependence is crucial to enable nurses in improving care and decreasing patient suffering. © 2015 Sigma Theta Tau International.

Middle school students' learning of the impact of methamphetamine abuse on the brain through serious game play

Science.gov (United States)

Cheng, Meng-Tzu

In response to the solicitation of the National Institute on Drug Use (NIDA) (NIDA, 2006) for the Development of a Virtual Reality Environment for Teaching about the Impact of Drug Abuse on the Brain, a virtual brain exhibit was developed by the joint venture of Entertainment Science, Inc. and Virtual Heroes, Inc.. This exhibit included a virtual reality learning environment combined with a video game, aiming at improving the neuroscience literacy of the general public, conveying knowledge about the impacts of methamphetamine abuse on the brain to the population, and establishing a stronger concept of drug use prevention among children. This study investigated the effectiveness of this interactive exhibit on middle school students' understanding and attitudes toward drug use. Three main research questions are addressed: (1) What do students learn about basic concepts of neuroscience and the impact of methamphetamine abuse on the brain via the exhibit? (2) How are students' attitudes toward methamphetamine use changed after exposure to the exhibit? (3) What are students' experiences and perceptions of using the exhibit to learn the impact of methamphetamine abuse on the brain? A mixed-method design, including pre/post/delayed-post test instruments, interviews, and video recordings, was conducted for 98 middle school students ranging from sixth to eighth grades to investigate these questions. The results show that students' understanding of the impact of methamphetamine abuse on the brain significantly improved after exposure to the exhibit regardless of grade or gender. Their pre-existing knowledge and their understanding after the exhibit indicated a tendency of progression. Most of the students consistently expressed negative attitudes toward general methamphetamine use regardless of whether it was before or after exposure to the exhibit. However, this exhibit gave them a better reason and made them feel more confident to refuse drugs. Finally, student learning

Prevalence of Primary Methamphetamine-Related Cases and Treatment-Centre Preparedness among Youth Outpatient Substance Abuse Treatment Centres in British Columbia, Canada

Science.gov (United States)

Callaghan, Russell C.; Rush, Brian; Tavares, Joey; Taylor, Lawren; Victor, J. Charles

2009-01-01

Adolescent methamphetamine use is a prominent concern for Canadian media and government. Few empirical studies, however, have established the scope of adolescent methamphetamine use or associated outpatient substance abuse treatment utilization. The current study aimed to answer the following questions: (1) What was the overall proportion of…

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

Science.gov (United States)

Womersley, Jacqueline S; Mpeta, Bafokeng; Dimatelis, Jacqueline J; Kellaway, Lauriston A; Stein, Dan J; Russell, Vivienne A

2016-06-17

Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague-Dawley comparator strains. Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague-Dawley strains but not in Wistar Kyoto rats. Our findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders.

Effects of chronic cocaine, morphine and methamphetamine on the mobility, immobility and stereotyped behaviors in crayfish.

Science.gov (United States)

Imeh-Nathaniel, Adebobola; Rincon, Natalia; Orfanakos, Vasiliki Bessie; Brechtel, Leanne; Wormack, Leah; Richardson, Erika; Huber, Robert; Nathaniel, Thomas I

2017-08-14

The worth of crayfish as a model system for studies of addiction was not previously recognized because a drug-reward phenomenon had not been documented in this model system. In our previous experiments, we demonstrate that the crayfish natural reward pathways are sensitive to human drugs of abuse. This finding supports crayfish as a suitable model to characterize specific behaviors that are relevant in drug addiction research, and the current study builds on our previous findings. The aim of the present study was to investigate unconditioned neurobehavioral effects of repeated treatment regimens using cocaine, morphine, and methamphetamine for three consecutive days. We analyzed mobility, immobility and characterized stereotypic behaviors following intracardial infusions of 2.0μg/g or 10.0μg/g doses of cocaine, morphine, and methamphetamine for three days. The results showed that systemic cocaine, morphine, and methamphetamine increased mobility at a low dose of 2.0μg/g more effectively than a high dose of 10.0μg/g, while simultaneously showing that the high dose exerted a more prominent effect in increasing immobility. Moreover, systemic cocaine, morphine, and methamphetamine injections have discerning effects towards a group of defined unconditioned stereotyped behavioral patterns associated with each drug, rather than a shared universal behavioral effect. These findings provide insight into the behavioral and pharmacological basis responsible for the unconditioned effects of these drugs in crayfish. Copyright © 2017. Published by Elsevier B.V.

3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter

Science.gov (United States)

Anneken, John H.; Angoa-Pérez, Mariana; Kuhn, Donald M.

2016-01-01

Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity. PMID:25626880

Neuroprotective Effects of Kolaviron, a Biflavonoid Complex of Garcinia kola, on Rats Hippocampus against Methamphetamine-Induced Neurotoxicity

OpenAIRE

Ijomone, Omamuyovwi M.; Nwoha, Polycarp U.; Olaibi, Olayemi K.; Obi, Augustine U.; Alese, Margaret O.

2012-01-01

Aim: To investigate the protective effects of kolaviron on brain weight and behavioural performance and the histology of the hippocampus of adult Wistar rats following methamphetamine challenge.Materials and Methods: Twenty four adult Wistar rats weighing between 150-200 g, randomly assigned into four groups of six each (Groups A, B, C, D) were used for this research. Group A served as control, while groups B and C were given single dose methamphetamine (10 mg/kg) intraperitoneally after grou...

Breaking Bad in Mississippi: Do County-Level Alcohol Sale Bans Encourage Crystal Methamphetamine Production and Consumption?

Directory of Open Access Journals (Sweden)

Granger Maury

2016-12-01

Full Text Available If alcohol has substitutes, changes in its relative price can encourage the production and consumption of other illicit and harmful drugs. This paper considers if county-level bans on the sale of alcohol in the state of Mississippi encourage the production and consumption of crystal methamphetamine. We estimate the parameters of a drug production function in which the inputs are the density of people and firms, underscoring the importance of learning and knowledge spillovers to production and consumption. Poisson and Negative Binomial parameter estimates reveal that county-level bans on hard liquor sales; but not on beer and wine, increase the number of crystal methamphetamine labs. In the absence of such laws, there would be approximately 308 fewer crystal methamphetamine labs in the state of Mississippi. Our findings suggest that in Mississippi, which is the least healthiest state in the nation, county-level bans on hard liquor sales are not welfare improving as they encourage substitution for a drug that is potentially more harmful to individual health than alcohol.

Development of a micropulverized extraction method for rapid toxicological analysis of methamphetamine in hair.

Science.gov (United States)

Miyaguchi, Hajime; Kakuta, Masaya; Iwata, Yuko T; Matsuda, Hideaki; Tazawa, Hidekatsu; Kimura, Hiroko; Inoue, Hiroyuki

2007-09-07

We developed a rapid sample preparation method for the toxicological analysis of methamphetamine and amphetamine (the major metabolite of methamphetamine) in human hair by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), to facilitate fast screening and quantitation. Two milligrams of hair were mechanically micropulverized for 5 min in a 2-ml plastic tube together with 100 microl of an aqueous solvent containing 10% acetonitrile, 100 mM trifluoroacetic acid and the corresponding deuterium analogues as internal standards. The pulverizing highly disintegrated the hair components, simultaneously allowing the extraction of any drugs present in the hair. After filtering the suspension with a membrane-filter unit, the clear filtrate was directly analyzed by HPLC-MS/MS. No evaporation processes were required for sample preparation. Method optimization and validation study were carried out using real-case specimens and fortified samples in which the drugs had been artificially absorbed, respectively. Concentration ranges for quantitation were 0.040-125 and 0.040-25 ng/mg for methamphetamine and amphetamine, respectively. Real-case specimens were analyzed by the method presented here and by conventional ones to verify the applicability of our method to real-world analysis. Our method took less than 30 min for a set of chromatograms to be obtained from a washed hair sample.

Levels of Neural Progenitors in the Hippocampus Predict Memory Impairment and Relapse to Drug Seeking as a Function of Excessive Methamphetamine Self-Administration

Science.gov (United States)

Recinto, Patrick; Samant, Anjali Rose H; Chavez, Gustavo; Kim, Airee; Yuan, Clara J; Soleiman, Matthew; Grant, Yanabel; Edwards, Scott; Wee, Sunmee; Koob, George F; George, Olivier; Mandyam, Chitra D

2012-01-01

Methamphetamine affects the hippocampus, a brain region crucial for learning and memory, as well as relapse to drug seeking. Rats self-administered methamphetamine for 1 h twice weekly (intermittent-short-I-ShA), 1 h daily (limited-short-ShA), or 6 h daily (extended-long-LgA) for 22 sessions. After 22 sessions, rats from each access group were withdrawn from self-administration and underwent spatial memory (Y-maze) and working memory (T-maze) tests followed by extinction and reinstatement to methamphetamine seeking or received one intraperitoneal injection of 5-bromo-2′-deoxyuridine (BrdU) to label progenitors in the hippocampal subgranular zone (SGZ) during the synthesis phase. Two-hour-old and 28-day-old surviving BrdU-immunoreactive cells were quantified. I-ShA rats performed better on the Y-maze and had a greater number of 2-h-old SGZ BrdU cells than nondrug controls. LgA rats, but not ShA rats, performed worse on the Y- and T-maze and had a fewer number of 2-h-old SGZ BrdU cells than nondrug and I-ShA rats, suggesting that new hippocampal progenitors, decreased by methamphetamine, were correlated with impairment in the acquisition of new spatial cues. Analyses of addiction-related behaviors after withdrawal and extinction training revealed methamphetamine-primed reinstatement of methamphetamine-seeking behavior in all three groups (I-ShA, ShA, and LgA), and this effect was enhanced in LgA rats compared with I-ShA and ShA rats. Protracted withdrawal from self-administration enhanced the survival of SGZ BrdU cells, and methamphetamine seeking during protracted withdrawal enhanced Fos expression in the dentate gyrus and medial prefrontal cortex in LgA rats to a greater extent than in ShA and I-ShA rats. These results indicate that changes in the levels of the proliferation and survival of hippocampal neural progenitors and neuronal activation of hippocampal granule cells predict the effects of methamphetamine self-administration (limited vs extended

Mephedrone Does not Damage Dopamine Nerve Endings of the Striatum but Enhances the Neurotoxicity of Methamphetamine, Amphetamine and MDMA

OpenAIRE

Angoa-Pérez, Mariana; Kane, Michael J.; Briggs, Denise I.; Francescutti, Dina M.; Sykes, Catherine E.; Shah, Mrudang M.; Thomas, David M.; Kuhn, Donald M.

2013-01-01

Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its reuptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamin...

Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys

OpenAIRE

Banks, Matthew L; Blough, Bruce E

2015-01-01

Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds:...

Mediators of interpersonal violence and drug addiction severity among methamphetamine users in Cape Town, South Africa.

Science.gov (United States)

Hobkirk, Andréa L; Watt, Melissa H; Green, Kimberly T; Beckham, Jean C; Skinner, Donald; Meade, Christina S

2015-03-01

South Africa has high rates of interpersonal violence and a rapidly growing methamphetamine epidemic. Previous research has linked experiences of interpersonal violence to higher rates of substance use, and identified mental health constructs as potential mediators of this association. The aim of this study was to examine the relationship between interpersonal violence and addiction severity among active methamphetamine users in Cape Town, South Africa, and to explore symptoms of posttraumatic stress disorder (PTSD) and substance use coping as mediators of this relationship. A community sample of 360 methamphetamine users was recruited through respondent driven sampling and surveyed on their experiences of violence, mental health, coping, and drug use and severity. A series of one-way ANOVAs were conducted to examine the relationship of self-reported interpersonal violence with drug addiction severity, and multiple mediation analyses were used to determine if PTSD symptoms and substance use coping mediated this relationship. The majority (87%) of the sample reported experiencing at least one instance of interpersonal violence in their lifetime, and the number of violent experiences was associated with increased drug addiction severity. PTSD and substance use coping were significant mediators of this association. Only the indirect effect of substance use coping remained significant for the female sample when the mediation model was conducted separately for men and women. The findings point to the need for integrated treatments that address drug use and PTSD for methamphetamine users in South Africa and highlight the importance of coping interventions for women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation of Er3+:Y3Al5O12/WO3-KNbO3 composite and application in treatment of methamphetamine under ultrasonic irradiation.

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Zhang, Hongbo; Huang, Yingying; Li, Guanshu; Wang, Guowei; Fang, Dawei; Song, Youtao; Wang, Jun

2017-03-01

Er 3+ :Y 3 Al 5 O 12 /WO 3 -KNbO 3 composite powder as an effective sonocatalyst was prepared via collosol-gelling-hydrothermal and high-temperature calcination methods. The textures of materials were observed by X-ray diffractometer (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). In order to estimate the sonocatalytic activity of Er 3+ :Y 3 Al 5 O 12 /WO 3 -KNbO 3 composite powder, the sonocatalytic degradation of methamphetamine (MAPA) was performed. Furthermore, the influences of mass ratio of WO 3 and KNbO 3 , ultrasonic irradiation time, catalyst addition amount, initial methamphetamine (MAPA) concentration and used times on the sonocatalytic degradation of methamphetamine (MAPA) caused by Er 3+ :Y 3 Al 5 O 12 /WO 3 -KNbO 3 composite powder were investigated by using gas chromatography. Under optimal conditions of 1.00g/L Er 3+ :Y 3 Al 5 O 12 /WO 3 -KNbO 3 addition amount and 10.00mg/L methamphetamine (MAPA) initial concentration, 68% of methamphetamine (MAPA) could be removed after 150min ultrasonic irradiation. The experimental results showed that the Er 3+ :Y 3 Al 5 O 12 /WO 3 -KNbO 3 as sonocatalyst displayed an excellent sonocatalytic activity in degradation of methamphetamine (MAPA) under ultrasonic irradiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Methamphetamine enhances Cryptococcus neoformans pulmonary infection and dissemination to the brain.

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Patel, Dhavan; Desai, Gunjan M; Frases, Susana; Cordero, Radames J B; DeLeon-Rodriguez, Carlos M; Eugenin, Eliseo A; Nosanchuk, Joshua D; Martinez, Luis R

2013-07-30

Methamphetamine (METH) is a major addictive drug of abuse in the United States and worldwide, and its use is linked to HIV acquisition. The encapsulated fungus Cryptococcus neoformans is the most common cause of fungal meningitis in patients with AIDS. In addition to functioning as a central nervous system stimulant, METH has diverse effects on host immunity. Using a systemic mouse model of infection and in vitro assays in order to critically assess the impact of METH on C. neoformans pathogenesis, we demonstrate that METH stimulates fungal adhesion, glucuronoxylomannan (GXM) release, and biofilm formation in the lungs. Interestingly, structural analysis of the capsular polysaccharide of METH-exposed cryptococci revealed that METH alters the carbohydrate composition of this virulence factor, an event of adaptation to external stimuli that can be advantageous to the fungus during pathogenesis. Additionally, we show that METH promotes C. neoformans dissemination from the respiratory tract into the brain parenchyma. Our findings provide novel evidence of the impact of METH abuse on host homeostasis and increased permissiveness to opportunistic microorganisms. Methamphetamine (METH) is a major health threat to our society, as it adversely changes people's behavior, as well as increases the risk for the acquisition of diverse infectious diseases, particularly those that enter through the respiratory tract or skin. This report investigates the effects of METH use on pulmonary infection by the AIDS-related fungus Cryptococcus neoformans. This drug of abuse stimulates colonization and biofilm formation in the lungs, followed by dissemination of the fungus to the central nervous system. Notably, C. neoformans modifies its capsular polysaccharide after METH exposure, highlighting the fungus's ability to adapt to environmental stimuli, a possible explanation for its pathogenesis. The findings may translate into new knowledge and development of therapeutic and public health

Working memory deficits affect risky decision-making in methamphetamine users with attention-deficit/hyperactivity disorder.

Science.gov (United States)

Duarte, Nichole A; Woods, Steven Paul; Rooney, Alexandra; Atkinson, J Hampton; Grant, Igor

2012-04-01

Methamphetamine (MA) use and Attention-Deficit/Hyperactivity Disorder (ADHD) commonly co-occur and are independently associated with dysregulation of frontostriatal loops and risky decision-making; however, whether their comorbidity exacerbates risky decision-making is not known. This study evaluated 23 participants with histories of MA dependence and ADHD (MA+ADHD+), 25 subjects with MA dependence alone (MA+ADHD-), and 22 healthy adults (MA-ADHD-), who completed the Iowa Gambling Task (IGT) as part of a larger neuropsychiatric research evaluation. Results showed a significant interaction between ADHD, MA, and working memory, such that individuals with working memory deficits in the MA+ADHD+ cohort demonstrated the strongest propensity to select cards from "disadvantageous" versus "advantageous" decks on the IGT. This effect was not better explained by other psychiatric, substance use, neuromedical, or cognitive factors. Findings suggest that working memory deficits may moderate the expression of risky decision-making in MA users with ADHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

A prospective study of methamphetamine use as a predictor of high school non-attendance in Cape Town, South Africa

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Parry Charles D

2010-10-01

Full Text Available Abstract Background This prospective study investigated the association between life-long methamphetamine and other drug use and high school non-attendance, in a sample of high school students in Cape Town, South Africa. Methods A random sample of 1535 high school students completed a baseline questionnaire in 2006, and were asked to complete a follow-up questionnaire 12 months later. The questionnaire included questions on substance use, including tobacco, alcohol, methamphetamine and cannabis use, demographic factors, and questions relating to school attendance and performance. Results Forty-three percent of the students surveyed at baseline did not complete a follow-up questionnaire after 12 months. Compared with students who were not using selected substances, an adjusted logistic regression model showed that life-time methamphetamine use in addition to other substances was significantly associated with non-attendance (OR = 2.58, 95% CI: 1.24 - 5.36 when other non-substance use factors (repeating a year at school and being older than the norm for current grade were taken into account. Conclusions Early identification of students with methamphetamine and other substance use problems, and a supportive rather than punitive school policy, may be valuable in improving high school completion and student retention rates.

Differentiation of ring-substituted regioisomers of amphetamine and methamphetamine by supercritical fluid chromatography.

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Segawa, Hiroki; T Iwata, Yuko; Yamamuro, Tadashi; Kuwayama, Kenji; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Inoue, Hiroyuki

2017-03-01

Chromatographic differentiation of the ring-substituted regioisomers of amphetamine (AMP) and methamphetamine (MA) was performed by supercritical fluid chromatography (SFC). The behaviour of the retention against the changes of column temperature and co-solvent proportion was studied. The obtained information facilitated the optimization of the each regioisomer. As a result, 2-, 3-, and 4-ring-substituted analogues of AMP and MA with methyl, methoxy, fluoro, chloro, and bromo groups were separated, generally within 6 min. In addition, we found that the separation pattern of the examined regioisomers was classified into two, which depended on the electron donating/withdrawing effect of the substituent. Our results indicate that SFC could be used in forensic drug analysis for fast, reliable identification of structurally similar drugs of abuse. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning

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Bharti AR

2016-04-01

Full Text Available Ajay R Bharti,1 Steven Paul Woods,2 Ronald J Ellis,3 Mariana Cherner,2 Debra Rosario,3 Michael Potter,3 Robert K Heaton,2 Ian P Everall,4 Eliezer Masliah,5 Igor Grant,2 Scott L Letendre1 On behalf of the Translational Methamphetamine AIDS Research Center Group 1Department of Medicine, 2Department of Psychiatry, 3Department of Neurosciences, University of California San Diego, San Diego, CA, USA; 4Department of Psychiatry, University of Melbourne, Victoria, Australia; 5Department of Pathology, University of Californa San Diego, San Diego, CA, USA Background: Human immunodeficiency virus (HIV and methamphetamine use commonly affect neurocognitive (NC functioning. We evaluated the relationships between NC functioning and two fibroblast growth factors (FGFs in volunteers who differed in HIV serostatus and methamphetamine dependence (MAD. Methods: A total of 100 volunteers were categorized into four groups based on HIV serostatus and MAD in the prior year. FGF-1 and FGF-2 were measured in cerebrospinal fluid by enzyme-linked immunosorbent assays along with two reference biomarkers (monocyte chemotactic protein [MCP]-1 and neopterin. Comprehensive NC testing was summarized by global and domain impairment ratings. Results: Sixty-three volunteers were HIV+ and 59 had a history of MAD. FGF-1, FGF-2, and both reference biomarkers differed by HIV and MAD status. For example, FGF-1 levels were lower in subjects who had either HIV or MAD than in HIV– and MAD– controls (P=0.003. Multivariable regression identified that global NC impairment was associated with an interaction between FGF-1 and FGF-2 (model R2=0.09, P=0.01: higher FGF-2 levels were only associated with neurocognitive impairment among subjects who had lower FGF-1 levels. Including other covariates in the model (including antidepressant use strengthened the model (model R2=0.18, P=0.004 but did not weaken the association with FGF-1 and FGF-2. Lower FGF-1 levels were associated with impairment

Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.

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Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

2014-04-01

We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.

Effect of exercise versus cognitive behavioural therapy or no intervention on anxiety, depression, fitness and quality of life in adults with previous methamphetamine dependency: a systematic review.

Science.gov (United States)

Morris, Linzette; Stander, Jessica; Ebrahim, Wardah; Eksteen, Stephanie; Meaden, Orissa Anna; Ras, Ané; Wessels, Annemarie

2018-01-16

Methamphetamine (MA) is a highly addictive psychostimulant used by approximately 52 million people worldwide. Chronic MA abuse leads to detrimental physiological and neurological changes, as well as increases in anxiety and depression, and decreases in overall fitness and quality of life. Exercise has been reported to possibly reverse physiological and neurological damage caused by previous MA use, and to reduce anxiety and depression in this population. The aim of this systematic review was to identify, clinically appraise and synthesise the available evidence for the effectiveness of exercise, compared to cognitive behavioural therapy (CBT), standard care or no intervention, on decreasing anxiety and depression and improving fitness and quality of life in previous MA users. Seven computerised databases were searched from inception to May 2017, namely Scopus, Cochrane Library, PubMed/MEDLINE, PEDro, CINAHL, and ScienceDirect. Search terms included exercise, methamphetamine, fitness measures, depression, anxiety and quality of life. Randomised and non-randomised controlled- or clinical trials and pilot studies, published in English, were considered for inclusion. Methodological quality was critically appraised according to the PEDro scale. Heterogeneity across studies regarding control groups and assessment intervals rendered meta analyses inappropriate for this review and results were thus described narratively using text and tables. Two hundred and fifty-one titles were identified following the initial search, and 14 potentially-relevant titles were selected and the abstracts reviewed. Three studies (two randomised controlled trials and one quasi-experimental pilot) were included, with an average PEDro score of 6.66. Exercise resulted in significantly lower depression and anxiety scores versus CBT (p = 0.001). Balance also significantly improved following exercise versus standard care (p exercise is effective in reducing anxiety and depression and

Methamphetamine Treatment Issues and Considerations among Men Who Have Sex with Men

Science.gov (United States)

Goodrich, Kristopher M.

2011-01-01

Methamphetamine use is epidemic among men who have sex with men (MSM), but treatment has lagged for this group. The author reviews literature concerning use, individual effects of the drug, and treatment for MSM and discusses implications for counselor training, future practice, and research.

Methamphetamine use and criminal behavior.

Science.gov (United States)

Gizzi, Michael C; Gerkin, Patrick

2010-12-01

This research seeks to broaden our understanding of methamphetamine's (meth's) place within the study of drugs and crime. Through extensive court records research and interviews with 200 offenders in local jails in western Colorado, this research contributes to the creation of a meth user profile and begins to identify the place of meth in the drug-crime nexus. The study compares the criminal behavior of meth users with other drug users, finding that meth users are more likely than other drug users to be drunk or high at the time of arrest and claim their crimes were related to drug use in other ways. A content analysis of criminal records demonstrates that meth users have more extensive criminal records and are more likely than other drug users to commit property crimes.

Personality of mothers of substance-dependent patients

Directory of Open Access Journals (Sweden)

David Baron

2010-04-01

Full Text Available David Baron1, Samir AbolMagd2, Salwa Erfan2, Mona El Rakhawy21Temple University School of Medicine, Philadelphia, PA, USA; 2University of Cairo School of Medicine, Cairo, EgyptAbstract: Drug addicts often come from dysfunctional families. The prevailing view in the literature is that mothers of drug-dependent patients can be characterized by strong emotional bonds and overprotection. Studies suggest that maternal rejection could be a major risk factor of developing drug addiction. This work is a continuation of our previous study of childhood parenting experiences of substance-dependent patients. The aims were to compare the personality profile of mothers of substance-dependent patients and that of mothers of matched control subjects; and to examine the relation between the personality of mothers of addicts, and severity of their offspring’s addiction. The study group consisted of 20 mothers of substance-dependent patients and a control group of 35 mothers of non-dependent subjects; mothers of both groups were age matched. Patients were diagnosed according to DSM IV criteria. Personalities of mothers of both groups were assessed using the Minnesota Multiphasic Personality Inventory (MMPI. Substance-dependent patients (sons were administered the Addiction Severity Index (ASI. The mean scores of the MMPI Scales were higher for mothers of dependent patients compared to mothers of non-dependent subjects. Scores on the depression, hysteria and paranoia scales were significantly higher for mothers of patients (P = 0.03, 0.02, and 0.03, respectively. There was a significant positive correlation between scores of hysteria, and psychopathic deviance and the ASI (P = 0.03 and 0.01, respectively. There were significant negative correlations between scores of social introversion and the ASI drug/alcohol use status (P = 0.007, and family history dimensions (P = 0.003. Mothers of substance-dependent patients showed disturbances in aspects of personalities

Personal values and meaning in the use of methamphetamine among HIV-positive men who have sex with men.

Science.gov (United States)

Chartier, Maggie; Araneta, Angela; Duca, Lindsey; McGlynn, Lawrence M; Gore-Felton, Cheryl; Goldblum, Peter; Koopman, Cheryl

2009-04-01

Our aim with this qualitative study was to understand the role of personal values, meaning, and impact of drug use among HIV-positive men who have sex with men (MSM) who struggle with methamphetamine use. Participants were 22 MSM recruited from an ethnically diverse county in the San Francisco Bay area of California. Grounded theory was used to analyze the data collected in individual interviews. Emergent constructs of context, meaning, and perceived impact were identified and are described in a theoretical narrative format. The importance of broadening our understanding of HIV and methamphetamine addiction and their interaction is highlighted. This study contributes to the understanding of the complexity of methamphetamine use within the specific population of MSM living with HIV/ AIDS, and suggests possible directions for addressing important maintaining factors like adaptive use and enhancing factors that could contribute to an individual's ability to make better choices based on meaning and personal values.

Treating methamphetamine-induced resistant psychosis with clozapine.

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Seddigh, Ruohollah; Keshavarz-Akhlaghi, Amir-Abbas; Shariati, Behnam

2014-01-01

Background. Methamphetamine-induced psychosis (MIP) in Iran has turned into a serious issue in terms of health and treatment, lacking any obvious treatment methods for its resistant cases. Aims of Case Report. In the present study, a number of two cases of treatment of MIP with clozapine, which were resistant to the treatment with other antipsychotics, have been reported. Both cases completely responded to the treatment in only 2 weeks and no signs of psychosis relapse were seen in an 8-9 follow-up. Conclusion. Because of its particular pharmacologic features, clozapine may be effective in treating MIP.

Chronic methamphetamine exposure produces a delayed, long-lasting memory deficit.

Science.gov (United States)

North, Ashley; Swant, Jarod; Salvatore, Michael F; Gamble-George, Joyonna; Prins, Petra; Butler, Brittany; Mittal, Mukul K; Heltsley, Rebecca; Clark, John T; Khoshbouei, Habibeh

2013-05-01

Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regimen of METH exposure in adolescent mice decreases hippocampal synaptic plasticity and produces a deficit in short-term memory. Contrary to our prediction, there was no change in the hippocampal plasticity or short-term memory when measured after 14 days of METH exposure. However, we found that at 7, 14, and 21 days of drug abstinence, METH-exposed mice exhibited a deficit in spatial memory, which was accompanied by a decrease in hippocampal plasticity. Our results support the interpretation that the deleterious cognitive consequences of neurotoxic levels of METH exposure may manifest and persist after drug abstinence. Therefore, therapeutic strategies should consider short-term as well as long-term consequences of methamphetamine exposure. Copyright © 2012 Wiley Periodicals, Inc.

Development of a piezoelectric sensor for the detection of methamphetamine.

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Romero Guerra, Maria; Chianella, Iva; Piletska, Elena V; Karim, Kal; Turner, Anthony P F; Piletsky, Sergey A

2009-08-01

A computationally designed molecularly imprinted polymer (MIP) specific for methamphetamine was used as a synthetic receptor for the development of a piezoelectric sensor. Several different protocols were tested for the immobilisation of the MIP onto the gold sensor surface. The developed MIP sensor had a detection limit for methamphetamine as low as 1 microg mL(-1). The effect of the addition of poly(vinyl acetate) (PVA) on the pre-polymerisation mixtures, which increases the porosity of the polymer layer, was also studied using an Atomic Force Microscope (AFM). PVA seemed to affect both the porosity and the binding kinetics of the polymers prepared in dimethylformamide (DMF). However, no clear effect on porosity and binding kinetics was observed when polymers were prepared in diglyme. Moreover, PVA did not appear to improve the amplitude of the sensor response. In conclusion, because of its excellent recognition ability in aqueous solutions, the sensor described in this work could be an ideal starting point for the development of a commercial device for fast, on-site or road-side testing of drugs of abuse in body fluids such as saliva.

The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitoxicity and Environmental, Metabolic and Oxidative Stress

National Research Council Canada - National Science Library

Yamamoto, Bryan

2002-01-01

.... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U.S...

The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress

National Research Council Canada - National Science Library

Yamamoto, Bryan

2005-01-01

.... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U.S...

Could Google Trends Be Used to Predict Methamphetamine-Related Crime? An Analysis of Search Volume Data in Switzerland, Germany, and Austria.

Science.gov (United States)

Gamma, Alex; Schleifer, Roman; Weinmann, Wolfgang; Buadze, Anna; Liebrenz, Michael

2016-01-01

To compare the time trends of Google search interest in methamphetamine and criminal offences related to this drug. Google Trends data for the search term "meth" was compared to methamphetamine-related crime statistics (incl. use, possession, and dealing) in Switzerland, Germany, and Austria for the years 2004-2016. Google data was availably monthly. Crime data was available yearly, and monthly values were imputed. On the country level, internet search trends for "meth" roughly paralleled relevant criminal activity. State-level data, which was available for Austria, showed more heterogeneity. Cross-correlations for yearly data almost always peaked at a lag time of 0 and coefficients were mostly between 0.7 and 1.0 on the country level, and between 0.5 to 1.0 on the state level. Monthly cross-correlations based on imputed values were substantially lower, ranging from 0 to 0.6. These results encourage the further evaluation by law enforcement authorities of Google search activity as a possible predictor of methamphetamine-related crime. However, several limitations, in particular the crude temporal resolution of available crime data, precluded a detailed assessment of the relationship between internet search trends and the development of methamphetamine-related crime in central Europe.

Different Levels in Orexin Concentrations and Risk Factors Associated with Higher Orexin Levels: Comparison between Detoxified Opiate and Methamphetamine Addicts in 5 Chinese Cities

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Haoran Zhang

2013-01-01

Full Text Available This study sought to explore the degree of orexin levels in Chinese opiate and methamphetamine addicts and the differences between them. The cross-sectional study was conducted among detoxified drug addicts from Mandatory Detoxification Center (MDC in five Chinese cities. Orexin levels were assayed with radioimmunoassay (RIA. Mann-Whitney U test and Kruskal-Wallis test were used to detect differences across groups, and logistic regression was used to explore the association between orexin levels and characteristics of demographic and drug abuse. Between November 2009 and January 2011, 285 opiates addicts, 112 methamphetamine addicts, and 79 healthy controls were enrolled. At drug withdrawal period, both opiate and methamphetamine addicts had lower median orexin levels than controls, and median orexin levels in opiate addicts were higher than those in methamphetamine addicts (all above P<0.05. Adjusted odds of the above median concentration of orexin were higher for injection than “chasing the dragon” (AOR = 3.1, 95% CI = 1.2–7.9. No significant factors associated with orexin levels of methamphetamine addicts were found. Development of intervention method on orexin system by different administration routes especially for injected opiate addicts at detoxification phase may be significant and was welcome.

Perceived Treatment Need and Latent Transitions in Heroin and Methamphetamine Polydrug Use among People who Inject Drugs in Tijuana, Mexico.

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Meacham, Meredith C; Roesch, Scott C; Strathdee, Steffanie A; Gaines, Tommi L

2018-01-01

People who inject drugs (PWID) in Tijuana, Mexico, use heroin and/or methamphetamine. While polydrug use is associated with HIV risk behavior, less is known about the stability of polydrug use patterns over time and how polydrug use is related to perceived treatment need. Within a cohort of PWID in Tijuana (N = 735) we sought to (1) characterize subgroups of polydrug and polyroute use from baseline to six months; (2) determine the probabilities of transitioning between subgroups; and (3) examine whether self-reported need for help for drug use modified these transition probabilities. Latent transition analysis (LTA) identified four latent statuses: heroin-only injection (38% at both baseline and follow-up); co-injection of heroin with methamphetamine (3% baseline, 15% follow-up); injection of heroin and methamphetamine (37% baseline, 32% follow-up); and polydrug and polyroute users who injected heroin and both smoked and injected methamphetamine (22% baseline, 14% follow-up). Heroin-only injectors had the highest probability of remaining in the same latent status at follow-up. The majority reported great or urgent need for treatment (51%) and these PWID had greater odds of transitioning to a higher-risk status at follow-up, emphasizing the need for evidence-based drug treatment options for PWID.

Differences in Reasons for Living in College Methamphetamine Users and Non-Users

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Ellis, Jon B.; Kaniuk, Andrea; Barnes, Jenny

2016-01-01

A number of studies suggest an association between substance use and suicidal behavior. However, relatively few studies have examined reasons for living, adaptive beliefs that prevent one from committing suicide, in substance using populations. The current study examines reasons for living and methamphetamine use in 240 college students.…

The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic and Oxidative Stress

National Research Council Canada - National Science Library

Yamamoto, Bryan

2001-01-01

.... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is rapidly becoming a widespread problem and drug of abuse throughout the U.S...

Pyrethroid as a Substance of Abuse

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Pravesh Sharma

2014-01-01

Full Text Available This is a case of a 22-year-old Hispanic male with a history of bipolar disorder and methamphetamine dependence who was admitted after presenting with suicidal ideations by slashing his throat with a machete. The patient had been smoking and inhaling “processed” pyrethroid for about eight weeks as an inexpensive methamphetamine substitute. He reported experiencing a “rush” similar to methamphetamine after using pyrethroid from liquid insecticide that had been heated (electrocuted or sprayed on hot metal sheets until it crystallized. The patient presented with no significant physical markings or findings but claimed to have his suicidal ideations precipitated by concerns of ill effects of pyrethroid on his health. He also had positive urine drug screen for methamphetamine, which he admitted to using on the day of admission. We conclude that it is important for physicians to maintain a high level of suspicion for alternate and uncommon substances of abuse as well as risks for suicidal tendencies in these patients.

The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic and Oxidative Stress

National Research Council Canada - National Science Library

Yamamoto, Bryan

2000-01-01

.... Similarly, the psycho stimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is rapidly becoming a widespread problem and drug of abuse throughout the U.S...

Methamphetamine craving induced in an online virtual reality environment.

Science.gov (United States)

Culbertson, Christopher; Nicolas, Sam; Zaharovits, Itay; London, Edythe D; De La Garza, Richard; Brody, Arthur L; Newton, Thomas F

2010-10-01

The main aim of this study was to assess self-reported craving and physiological reactivity in a methamphetamine virtual reality (METH-VR) cue model created using Second Life, a freely available online gaming platform. Seventeen, non-treatment seeking, individuals that abuse methamphetamine (METH) completed this 1-day, outpatient, within-subjects study. Participants completed four test sessions: 1) METH-VR, 2) neutral-VR, 3) METH-video, and 4) neutral-video in a counterbalanced (Latin square) fashion. The participants provided subjective ratings of urges to use METH, mood, and physical state throughout each cue presentation. Measures of physiological reactivity (heart rate variability) were also collected during each cue presentation and at rest. The METH-VR condition elicited the greatest change in subjective reports of "crave METH", "desire METH", and "want METH" at all time points. The "high craving" participants displayed more high frequency cardiovascular activity while the "low craving" participants displayed more low frequency cardiovascular activity during the cue conditions, with the greatest difference seen during the METH-VR and METH-video cues. These findings reveal a physiological divergence between high and low craving METH abusers using heart rate variability, and demonstrate the usefulness of VR cues for eliciting subjective craving in METH abusers, as well as the effectiveness of a novel VR drug cue model created within an online virtual world. (c) 2010 Elsevier Inc. All rights reserved.

Dopamine transporter density of the basal ganglia assessed with I-123 IPT SPECT in methamphetamine abusers

International Nuclear Information System (INIS)

Lee, Joo Ryung; Ahn, Byeong Cheol; Kewm, Do Hun

2005-01-01

Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, ρ =0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT. Abuser group had lower basal ganglia DAT SBR than that of control (2.38 ± 0.20 vs 3.04 ± 0.27, ρ =0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, ρ =0.012, r=-0.924, ρ =0.009) This results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers

Dopamine transporter density of the basal ganglia assessed with I-123 IPT SPECT in methamphetamine abusers

Energy Technology Data Exchange (ETDEWEB)

Lee, Joo Ryung; Ahn, Byeong Cheol [Kyungpook National University Medical School, Daegu (Korea, Republic of); Kewm, Do Hun [National Bugok Mental Hospital, Changryung (Korea, Republic of)] (and others)

2005-10-15

Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, {rho} =0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT. Abuser group had lower basal ganglia DAT SBR than that of control (2.38 {+-} 0.20 vs 3.04 {+-} 0.27, {rho} =0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, {rho} =0.012, r=-0.924, {rho} =0.009) This results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers.

The management of methamphetamine use in sexual settings among men who have sex with men in Malaysia.

Science.gov (United States)

Lim, Sin How; Akbar, Mohd; Wickersham, Jeffrey A; Kamarulzaman, Adeeba; Altice, Frederick L

2018-03-28

The intentional use of illicit drugs for sexual purposes (also known as 'chemsex') is well known within the MSM communities in Malaysia although research in this population is scarce primarily because both drug use and homosexuality are illegal and stigmatised in Malaysia. From April to December 2014, interviews were conducted with twenty men (age range 21-43) living in Greater Kuala Lumpur who had sexual intercourse with other men in the past 6 months and who used illicit drugs at least monthly in the past 3 months. Fourteen men were recruited via gay social networking smartphone applications or websites while six were referred by the participants. Data were analsed using thematic analytic approach. The average duration of illicit drug use was 6.4 years (range 1-21) and all participants were using methamphetamine ("ice" or crystal meth) with frequency of use ranged from daily to once a month. Participants came from diverse ethnic, economic, and occupational backgrounds. Most participants used an inhalation apparatus ("bong") to consume methamphetamine and injection was rare in the sample. The primary motivation of methamphetamine use was to increase sexual capacity, heighten sexual pleasure and enhance sexual exploration and adventurism. Socializing with friends ("chilling"), and increased energy for work were secondary motivations. Participants emphasized the need to control the use of methamphetamine and some have established rules to control the amount and duration of use and a minority of men have maintained condom use during anal sex while under the influence of methamphetamine. Participants who professed to be in control of their drug use characterized themselves as functional users regardless of the health and social consequences from continuing use. Overall, participants perceived themselves differently from the traditional opioid users and reported limited access to sexual health and substance use treatment services. There is a need to increase access to

The Economic Cost of Methamphetamine Use in the United States, 2005

Science.gov (United States)

Nicosia, Nancy; Pacula, Rosalie Liccardo; Kilmer, Beau; Lundberg, Russell; Chiesa, James

2009-01-01

This first national estimate suggests that the economic cost of methamphetamine (meth) use in the United States reached $23.4 billion in 2005. Given the uncertainty in estimating the costs of meth use, this book provides a lower-bound estimate of $16.2 billion and an upper-bound estimate of $48.3 billion. The analysis considers a wide range of…

Involvement of Protein Phosphatases in the Destabilization of Methamphetamine-Associated Contextual Memory

Science.gov (United States)

Yu, Yang-Jung; Huang, Chien-Hsuan; Chang, Chih-Hua; Gean, Po-Wu

2016-01-01

Destabilization refers to a memory that becomes unstable when reactivated and is susceptible to disruption by amnestic agents. Here we delineated the cellular mechanism underlying the destabilization of drug memory. Mice were conditioned with methamphetamine (MeAM) for 3 d, and drug memory was assessed with a conditioned place preference (CPP)…

Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

International Nuclear Information System (INIS)

Nakamura, Hitoshi

2001-01-01

I investigated the differences in brain pharmacokinetics of [ 11 C]methamphetamine ([ 11 C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [ 11 C]MAP was synthesized by an automated on-line [ 11 C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [ 11 C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [ 11 C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Hitoshi [Tohoku Univ., Sendai (Japan). Hospital

2001-08-01

I investigated the differences in brain pharmacokinetics of [{sup 11}C]methamphetamine ([{sup 11}C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [{sup 11}C]MAP was synthesized by an automated on-line [{sup 11}C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [{sup 11}C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [{sup 11}C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

Short circuit: Disaggregation of adrenocorticotropic hormone and cortisol levels in HIV-positive, methamphetamine-using men who have sex with men.

Science.gov (United States)

Carrico, Adam W; Rodriguez, Violeta J; Jones, Deborah L; Kumar, Mahendra

2018-01-01

This study examined if methamphetamine use alone (METH + HIV-) and methamphetamine use in combination with HIV (METH + HIV+) were associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation as well as insulin resistance relative to a nonmethamphetamine-using, HIV-negative comparison group (METH-HIV-). Using an intact groups design, serum levels of HPA axis hormones in 46 METH + HIV- and 127 METH + HIV+ men who have sex with men (MSM) were compared to 136 METH-HIV- men. There were no group differences in prevailing adrenocorticotropic hormone (ACTH) or cortisol levels, but the association between ACTH and cortisol was moderated by METH + HIV+ group (β = -0.19, p < .05). Compared to METH-HIV- men, METH + HIV+ MSM displayed 10% higher log 10 cortisol levels per standard deviation lower ACTH. Both groups of methamphetamine-using MSM had lower insulin resistance and greater syndemic burden (i.e., sleep disturbance, severe depression, childhood trauma, and polysubstance use disorder) compared to METH-HIV- men. However, the disaggregated functional relationship between ACTH and cortisol in METH + HIV+ MSM was independent of these factors. Further research is needed to characterize the bio-behavioral pathways that explain dysregulated HPA axis functioning in HIV-positive, methamphetamine-using MSM. Copyright © 2017 John Wiley & Sons, Ltd.

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

International Nuclear Information System (INIS)

Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao; Liu, Zengxun; Sun, Jinhao

2015-01-01

Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Energy Technology Data Exchange (ETDEWEB)

Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao [Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012 (China); Liu, Zengxun [Department of Psychiatry, School of Medicine, Shandong University, Jinan, Shandong, 250012 China (China); Sun, Jinhao, E-mail: sunjinhao@gmail.com [Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012 (China)

2015-09-25

Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway.

Neuroprotective targets through which 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), a sigma receptor ligand, mitigates the effects of methamphetamine in vitro

Science.gov (United States)

Kaushal, Nidhi; Robson, Matthew J.; Rosen, Abagail; McCurdy, Christopher R.; Matsumoto, Rae R.

2014-01-01

Exposure to high or repeated doses of methamphetamine can cause hyperthermia and neurotoxicity, which are thought to increase the risk of developing a variety of neurological conditions. Sigma receptor antagonism can prevent methamphetamine-induced hyperthermia and neurotoxicity, but the underlying cellular targets through which the neuroprotection is conveyed remain unknown. Differentiated NG108-15 cells were thus used as a model system to begin elucidating the neuroprotective mechanisms targeted by sigma receptor antagonists to mitigate the effects of methamphetamine. In differentiated NG108-15 cells, methamphetamine caused the generation of reactive oxygen/nitrogen species, an increase in PERK-mediated endoplasmic reticulum stress and the activation of caspase-3, -8 and -9, ultimately resulting in apoptosis at micromolar concentrations, and necrotic cell death at higher concentrations. The sigma receptor antagonist, 6-acetyl-3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one (SN79), attenuated methamphetamine-induced increases in reactive oxygen/nitrogen species, activation of caspase-3,-8 and-9 and accompanying cellular toxicity. In contrast, 1,3-di(2-tolyl)-guanidine (DTG), a sigma receptor agonist, shifted the dose response curve of methamphetamine-induced cell death towards the left. To probe the effect of temperature on neurotoxicity, NG108-15 cells maintained at an elevated temperature (40 °C) exhibited a significant and synergistic increase in cell death in response to methamphetamine, compared to cells maintained at a normal cell culture temperature (37 °C). SN79 attenuated the enhanced cell death observed in the methamphetamine-treated cells at 40 °C. Together, the data demonstrate that SN79 reduces methamphetamine-induced reactive oxygen/nitrogen species generation and caspase activation, thereby conveying neuroprotective effects against methamphetamine under regular and elevated temperature conditions. PMID:24380829

Matrix-assisted laser desorption/ionization mass spectrometric imaging for the rapid segmental analysis of methamphetamine in a single hair using umbelliferone as a matrix.

Science.gov (United States)

Wang, Hang; Wang, Ying

2017-07-04

Segmental hair analysis offers a longer period for retrospective drug detection than blood or urine. Hair is a keratinous fiber and is strongly hydrophobic. The embedding of drugs in hydrophobic hair at low concentrations makes it difficult for extraction and detection with matrix-assisted laser desorption/ionization (MALDI) coupled with mass spectrometric imaging (MSI). In this study, a single scalp hair was longitudinally cut with a cryostat section to a length of 4 mm and fixed onto a stainless steel MALDI plate. Umbelliferone was used as a new hydrophobic matrix to enrich and assist the ionization efficiency of methamphetamine in the hair sample. MALDI-Fourier transform ion cyclotron resonance (FTICR)-MS profiling and imaging were performed for direct detection and mapping of methamphetamine on the longitudinal sections of the single hair sample in positive ion mode. Using MALDI-MSI, the distribution of methamphetamine was observed throughout five longitudinally sectioned hair samples from a drug abuser. The changes of methamphetamine were also semi-quantified by comparing the ratios of methamphetamine/internal standard (I.S). This method improves the detection sensitivity of target drugs embedded in a hair matrix for imaging with mass spectrometry. The method could provide a detection level of methamphetamine down to a nanogram per milligram incorporated into hair. The results were also compared with the conventional high performance liquid chromatography -tandem mass spectrometry (HPLC-MS/MS) method. Changes in the imaging results over time by the MSI method showed good semi-quantitative correlation to the results from the HPLC-MS/MS method. This study provides a powerful tool for drug abuse control and forensic medicine analysis in a narrow time frame, and a reduction in the sample amount required. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex differences in methamphetamine seeking in rats: Impact of oxytocin

OpenAIRE

Cox, Brittney M.; Young, Amy B.; See, Ronald E.; Reichel, Carmela M.

2013-01-01

Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1 mg/kg, IP) would decrease meth seeking in female...

Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine

Directory of Open Access Journals (Sweden)

Wise Phyllis M

2001-03-01

Full Text Available Abstract Background Human immunodeficiency virus (HIV infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness.To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. Results Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. Conclusion Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.

The disruptive effects of methamphetamine on delayed-matching-to-sample performance reflect proactive interference and are reduced by SCH23390.

Science.gov (United States)

Macaskill, Anne C; Harrow, Catherine C; Harper, David N

2015-01-01

Different drugs produce different patterns of impairment on delayed matching-to-sample tasks. For example, (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces an increase in proactive interference. That is, subjects are less accurate when they are required to make a response different to the one they made on the immediately previous trial. The current study assessed whether methamphetamine also produces this particular pattern of disruption in delayed matching-to-sample performance in rats. Methamphetamine primarily reduced accuracy on trials where the correct response differed from the one made on the previous trial. Thus methamphetamine, like MDMA and other stimulant-based drugs of abuse, increased proactive interference. This impairment was reduced by prior administration of the dopamine D1 antagonist SCH23390. These results further extend a general conclusion that a range of stimulant-based drugs may disrupt working memory function indirectly via a tendency to repeat previously made responses and that this disruption is related to D1 receptor activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Naloxone Induces Frequent Jumping after Chronic Morphine and Methamphetamine Co-Administration in Rats

Directory of Open Access Journals (Sweden)

Gholamreza Kaka

2014-02-01

Full Text Available Combined use of an opioid with a psychostimulant is popular among drug abusers. Such “polydrug use” may increase drug effects or attenuate adverse effects of either drug alone. We proposed that a combination of methamphetamine (meth and morphine may change physical opioid withdrawal symptoms. Adult male rats were chronically injected with cumulative subcutaneous (s.c. doses of morphine, meth or a combination of both drugs within five days. On day six, a challenge dose of the same drug was injected. Two hours later, precipitated withdrawal symptoms were scored within 30 minutes after naloxone (1mg/kg, i.p. injection. Both frequency and incidence of jumping significantly increased in combined treated animals (P<0.05. The sole emergent symptom in combined treated animals was digging which we consider as another escaping behavior in addition to jumping. Our findings imply that combined use of meth and morphine may exacerbate averseness of morphine withdrawal which may cause more intense opioid dependence

Prevalence and Correlates of Heroin–Methamphetamine Co-Injection Among Persons Who Inject Drugs in San Diego, California, and Tijuana, Baja California, Mexico

Science.gov (United States)

Meacham, Meredith C.; Strathdee, Steffanie A.; Rangel, Gudelia; Armenta, Richard F.; Gaines, Tommi L.; Garfein, Richard S.

2016-01-01

Objective: Although persons who inject drugs (PWID) in the western United States–Mexico border region are known to inject both heroin and methamphetamine, little is known about the prevalence and risks associated with co-injection of this depressant–stimulant combination (also known as “goofball” and “Mexican speedball”). Method: Baseline data from parallel cohort studies of PWID conducted concurrently in San Diego, CA, and Tijuana, Mexico, were used to estimate the prevalence and identify correlates of heroin–methamphetamine co-injection. PWID older than 18 years of age who reported injecting illicit drugs in the past month (N = 1,311; 32.7% female) were recruited in San Diego (n = 576) and Tijuana (n = 735) and completed interviewer-administered questionnaires. Bivariate and multivariable logistic regression analyses were used to identify correlates of heroin–methamphetamine co-injection. Results: The prevalence of co-injection in the past 6 months was 39.9% overall and was higher in Tijuana (55.8%) than in San Diego (19.8%). In multivariable analyses adjusting for study cohort, distributive syringe sharing, purchasing syringes prefilled with drugs, finding it hard to get new syringes, reporting great or urgent need for treatment, and younger age were independently associated with co-injection. Past-6-month overdose was significantly associated with higher odds of co-injection in San Diego than in Tijuana. Conclusions: These findings indicate that heroin–methamphetamine co-injection is more common in Tijuana than in San Diego, yet this practice was only associated with overdose in San Diego. Heroin–methamphetamine co-injection was also independently associated with HIV-associated injection risk behaviors. Overdose-prevention interventions should address co-injection of depressants and stimulants. PMID:27588536

Effects of methamphetamine and its primary human metabolite, p-hydroxymethamphetamine, on the development of the Australian blowfly Calliphora stygia.

Science.gov (United States)

Mullany, Christina; Keller, Paul A; Nugraha, Ari S; Wallman, James F

2014-08-01

The larvae of necrophagous fly species are used as forensic tools for the determination of the minimum postmortem interval (PMI). However, any ingested drugs in corpses may affect larval development, thus leading to incorrect estimates of the period of infestation. This study investigated the effects of methamphetamine and its metabolite, p-hydroxymethamphetamine, on the forensically important Australian blowfly Calliphora stygia. It was found that the presence of the drugs significantly accelerated larval growth and increased the size of all life stages. Furthermore, drug-exposed samples remained as pupae for up to 78 h longer than controls. These findings suggest that estimates of the minimum PMI of methamphetamine-dosed corpses could be incorrect if the altered growth of C. stygia is not considered. Different temperatures, drug concentrations and substrate types are also likely to affect the development of this blowfly. Pending further research, the application of C. stygia to the entomological analysis of methamphetamine-related fatalities should be appropriately qualified. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Breaking Bad Delirium: Methamphetamine and Boric Acid Toxicity with Hallucinations and Pseudosepsis.

Science.gov (United States)

Johnson, Kayla; Stollings, Joanna L; Ely, E Wesley

2017-02-01

A 30-year-old patient presented with hallucinations and profound shock. He was initially misdiagnosed as having severe sepsis; once ingestions were considered, he was diagnosed as potentially having arsenic toxicity. The clinical story reveals many instructional lessons that could aid in the evaluation and management of future patients. This man presented with large amounts of blue crystals around his nose and lips from inhaling and eating boric acid (an ant poison) so he could, as he put it, kill the ants "pouring into my mouth and nose and up into my brain." His profound pseudosepsis and sustained delirium were induced by co-ingestion of methamphetamine and a large quantity of boric acid. Delirium is a form of acute brain dysfunction that often is multifactorial in critical illness and, when seen in septic shock, is associated with prolonged mechanical ventilation, increased length of hospital stay, medical costs, higher mortality, and long-term cognitive impairment resembling dementia. Pseudosepsis is a noninfectious condition most commonly seen with ingestions such as salicylate (aspirin) toxicity. This report emphasizes the need to recognize agents that contain boric acid as an etiology of unexplained delirium and profound shock.

Methamphetamine Exposure, Iron Deficiency, and Implications for Cognitive-Communicative Function: A Case Study

Science.gov (United States)

Goldberg, Lynette R.; Heiss, Cynthia J.; White, Letitia; Kaf, Wafaa A.; Becker, Alan; Schindler, Jessica B.; Dion, Nancy; Oswalt, Jill

2010-01-01

Methamphetamine (meth) exposure during fetal development has the potential to adversely affect the development of multiple organ systems. An interdisciplinary case study of a 4-year 11-month-old child born to a mother addicted to meth revealed significant cognitive and communicative delays. Possible meth-related consequences for these delays…

Examining Correlates of Methamphetamine and Other Drug Use in Pregnant American Indian Adolescents

Science.gov (United States)

Barlow, Allison; Mullany, Britta C.; Neault, Nicole; Davis, Yvonne; Billy, Trudy; Hastings, Ranelda; Coho-Mescal, Valerie; Lake, Kristin; Powers, Julia; Clouse, Emily; Reid, Raymond; Walkup, John T.

2010-01-01

American Indian and Alaska Native (AI/AN) adolescents have high rates of pregnancy, as well as alcohol, marijuana, cocaine, and, increasingly, methamphetamine (meth) use. The progression of adolescent drug use to meth use could have devastating impacts on AI communities, particularly when youth are simultaneously at risk for teen childbearing. In…

Chronic Methamphetamine Exposure Produces a Delayed, Long-Lasting Memory Deficit

OpenAIRE

North, Ashley; Swant, Jarod; Salvatore, Michael F.; Gamble-George, Joyonna; Prins, Petra; Butler, Brittany; Mittal, Mukul K.; Heltsley, Rebecca; Clark, John T.; Khoshbouei, Habibeh

2013-01-01

Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Whether this is due to long-term deficits in short-term memory and/or hippocampal plasticity remains unclear. Recently, we reported that METH increases baseline synaptic transmission and reduces LTP in an ex vivo preparation of the hippocampal CA1 region from young mice. In the current study, we tested the hypothesis that a repeated neurotoxic regi...

A Web-Based Toolkit to Provide Evidence-Based Resources About Crystal Methamphetamine for the Australian Community: Collaborative Development of Cracks in the Ice.

Science.gov (United States)

Champion, Katrina Elizabeth; Chapman, Cath; Newton, Nicola Clare; Brierley, Mary-Ellen; Stapinski, Lexine; Kay-Lambkin, Frances; Nagle, Jack; Teesson, Maree

2018-03-20

The use of crystal methamphetamine (ice) and the associated harms for individuals, families, and communities across Australia has been the subject of growing concern in recent years. The provision of easily accessible, evidence-based, and up-to-date information and resources about crystal methamphetamine for the community is a critical component of an effective public health response. This paper aims to describe the codevelopment process of the Web-based Cracks in the Ice Community Toolkit, which was developed to improve access to evidence-based information and resources about crystal methamphetamine for the Australian community. Development of the Cracks in the Ice Community Toolkit was conducted in collaboration with community members across Australia and with experts working in the addiction field. The iterative process involved the following: (1) consultation with end users, including community members, crystal methamphetamine users, families and friends of someone using crystal methamphetamine, health professionals, and teachers (n=451) via a cross-sectional Web-based survey to understand information needs; (2) content and Web development; and (3) user testing of a beta version of the Web-based toolkit among end users (n=41) and experts (n=10) to evaluate the toolkit's acceptability, relevance, and appeal. Initial end user consultation indicated that the most commonly endorsed reasons for visiting a website about crystal methamphetamine were "to get information for myself" (185/451, 41.0%) and "to find out how to help a friend or a family member" (136/451, 30.2%). Community consultation also revealed the need for simple information about crystal methamphetamine, including what it is, its effects, and when and where to seek help or support. Feedback on a beta version of the toolkit was positive in terms of content, readability, layout, look, and feel. Commonly identified areas for improvement related to increasing the level of engagement and personal connection

Development of an evidence-based, gay-specific cognitive behavioral therapy intervention for methamphetamine-abusing gay and bisexual men.

Science.gov (United States)

Reback, Cathy J; Shoptaw, Steven

2014-08-01

This study compared outcomes in methamphetamine use and sexual risk behaviors from a modified gay-specific, cognitive behavioral therapy (GCBT) combined with a low-cost contingency management (CM; [GCBT+CM]) intervention to prior findings from clinical trials of the original GCBT. Effect sizes for primary outcomes were compared using meta analysis. Comparisons of effect sizes at end of treatment showed the modified GCBT+CM produced significantly fewer consecutive weeks of methamphetamine abstinence (-0.44, CI: -0.79, -0.09) and fewer male sexual partners (-0.36, CI: -0.71, -0.02) than the first trial of GCBT, and more days of methamphetamine use (0.35, CI: 0.02, 0.68) than the second trial of GCBT. At 26-week follow-up, the modified GCBT+CM produced greater effects in reducing the number of male sexual partners (-0.54, CI: -0.89, -0.19; -0.51, CI: -0.84, -0.18). The original GCBT produced more and mostly short-term beneficial drug use outcomes, though sexual behavior changes consistently favored the modified GCBT+CM. On balance, most benefits are retained with the modified GCBT+CM intervention. Copyright © 2011 Elsevier Ltd. All rights reserved.

Insular neural system controls decision-making in healthy and methamphetamine-treated rats.

Science.gov (United States)

Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

2015-07-21

Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making.

Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration.

Science.gov (United States)

Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm Christopher; Smith, Davey M

2007-01-01

Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Cross-sectional analysis. Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI.

Investigating the Role of Serotonin in Methamphetamine Psychosis: Unaltered Behavioral Effects of Chronic Methamphetamine in 5-HT1A Knockout Mice

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Maarten van den Buuse

2017-04-01

Full Text Available Methamphetamine (Meth is a widely abused stimulant drug, but this abuse is associated with an increased risk of developing psychosis. In addition to its well-known action on brain dopamine, Meth also affects serotonergic (5-HT neurons. The aim of this study was to investigate this role in mice, which lack one of the main serotonin receptors, the 5-HT1A receptor, which has been implicated in both schizophrenia and Meth-induced psychosis. Male and female wild-type or 5-HT1A knockout (KO mice received daily treatment with increasing doses of methamphetamine from 6 to 9 weeks of age (1–4 mg/kg/day twice a day. At least 2 weeks after the last injection, the mice underwent a battery of behavioral tests focusing on psychosis-related behaviors, including Meth-induced hyperactivity, prepulse inhibition (PPI, social interaction, elevated plus maze (EPM, and Y-maze. Meth pretreatment resulted in significantly increased hyperlocomotion in response to an acute Meth challenge, but this effect was independent of genotype. Chronic Meth treatment resulted in decreased levels of anxiety in the EPM in both sexes, as well as increased startle responses in female mice only, again independent of genotype. 5-HT1A KO mice showed an increased locomotor response to acute Meth in both sexes, as well as increased PPI and decreased startle responses in female mice only, independent of Meth pretreatment. In conclusion, the effects of chronic Meth appear unaffected by the absence of the 5-HT1A receptor. These results do not support a role of the 5-HT1A receptor in Meth-induced psychosis.

Demonstrating the process of community innovation: the Indian Country Methamphetamine Initiative.

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Walker, R Dale; Bigelow, Douglas A; LePak, Jessica Hope; Singer, Michelle J

2011-01-01

In 2007 the federal Department of Health and Human Services, Office for Minority Health, collaborating with other federal agencies, sponsored the Indian Country Methamphetamine Initiative (ICMI). ICMI was undertaken to create community-driven, culture-based best practices in methamphetamine prevention and treatment which could then be disseminated throughout Indian Country. The ICMI ultimately involved ten tribes and five national organizations. Each tribe established a coalition of community government, nongovernment agencies, and elements of civic society to develop a comprehensive assessment, plan, and then to implement the plan. Each tribal coalition planned a complex array of activities including treatment programs, public education and mobilization, law enforcement strategies, and other intervention strategies, each intervention described within a logic model. These interventions focused on logic modeling; coalitions; capacity development and service system optimization; law enforcement and justice; individual and family treatment; public information, awareness, and education; community mobilization; and a very popular ICMI strategy, cultural renaissance. It was concluded that worthwhile activities were conducted under ICMI sponsorship, but that the specific aim of demonstrating community-driven, culture-based innovations in a manner suitable for dissemination was achieved only to a limited extent. Based on this outcome together with similar experiences, recommendations for future initiatives are suggested.

Predictors of patient dependence in mild-to-moderate Alzheimer's disease.

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Benke, Thomas; Sanin, Günter; Lechner, Anita; Dal-Bianco, Peter; Ransmayr, Gerhard; Uranüs, Margarete; Marksteiner, Josef; Gaudig, Maren; Schmidt, Reinhold

2015-01-01

Patient dependence has rarely been studied in mild-to-moderate Alzheimer's disease (AD). To identify factors which predict patient dependence in mild-to-moderate AD. We studied 398 non-institutionalized AD patients (234 females) of the ongoing Prospective Registry on Dementia (PRODEM) in Austria. The Dependence Scale (DS) was used to assess patient dependence. Patient assessment comprised functional abilities, neuropsychiatric symptoms and cognitive functions. A multiple linear regression analysis was performed to identify predictors of patient dependence. AD patients were mildly-to-moderately impaired (mean scores and SDs were: CDR 0.84 ± 0.43; DAD 74.4 ± 23.3, MMSE = 22.5 ± 3.6). Psychopathology and caregiver burden were in the low range (mean NPI score 13.2, range 0 to 98; mean ZBI score 18, range 0-64). Seventy five percent of patients were classified as having a mild level of patient dependence (DS sum score 0 to 6). Patient dependence correlated significantly and positively with age, functional measures, psychopathology and depression, disease duration, and caregiver burden. Significant negative, but low correlations were found between patient dependence, cognitive variables, and global cognition. Activities of daily living, patient age, and disease severity accounted for 63% of variance in patient dependence, whereas cognitive variables accounted for only 11%. Dependence in this cohort was mainly related to age and functional impairment, and less so to cognitive and neuropsychiatric variables. This differs from studies investigating patients in more advanced disease stages which found abnormal behavior and impairments of cognition as main predictors of patient dependence.

Overexpression of parkin in rat nigrostriatal dopamine system protects against methamphetamine neurotoxicity

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Liu, Bin; Traini, Roberta; Killinger, Bryan; Schneider, Bernard; Moszczynska, Anna

2013-01-01

Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum, sparing other striatal terminals and cell bodies. We previously detected a deficit in parkin after binge METH in rat striatal synaptosomes. Parkin is an ubiquitin-protein E3 ligase capable of protecting dopamine neurons from diverse cellular insults. Whether the deficit in parkin mediates the toxicity of METH and whether parkin can protect from toxicity of the drug is unknown. The present study investigated whether overexpression of parkin attenuates degeneration of striatal dopaminergic terminals exposed to binge METH. Parkin overexpression in rat nigrostriatal dopamine system was achieved by microinjection of adeno-associated viral transfer vector 2/6 encoding rat parkin (AAV2/6-parkin) into the substantia nigra pars compacta. The microinjections of AAV2/6-parkin dose-dependently increased parkin levels in both the substantia nigra pars compacta and striatum. The levels of dopamine synthesizing enzyme, tyrosine hydroxylase, remained at the control levels; therefore, tyrosine hydroxylase immunoreactivity was used as an index of dopaminergic terminal integrity. In METH-exposed rats, the increase in parkin levels attenuated METH-induced decreases in striatal tyrosine hydroxylase immunoreactivity in a dose-dependent manner, indicating that parkin can protect striatal dopaminergic terminals against METH neurotoxicity. PMID:23313192

Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives.

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Kraemer, Thomas; Maurer, Hans H

2002-04-01

This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3;,4;-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine; R,S-1-(1;,3;-benzodioxol-5;-yl)-2-butanamine or R,S-1-(3;,4;-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.

Capillary electrophoretic enantioseparation of selegiline, methamphetamine and ephedrine using a neutral β-cyclodextrin epichlorhydrin polymer

NARCIS (Netherlands)

Sevcik, J.; Stransky, Z.; Ingelse, B.A.; Lemr, K.

1996-01-01

This paper describes the development of a capillary zone electrophoretic method for chiral separation of three basic compounds of the selegiline synthetic pathway: ephedrine, methamphetamine and selegiline. The method developed allows one to separate the studied compounds in one run using a neutral

Emotional awareness in substance-dependent patients.

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Carton, Solange; Bayard, Sophie; Paget, Virginie; Jouanne, Céline; Varescon, Isabelle; Edel, Yves; Detilleux, Michel

2010-06-01

We explored emotional awareness in substance-dependent patients and its relationships to self-reported alexithymia. Sixty-four outpatients with drug dependence or alcohol dependence were evaluated before the beginning of treatment with the Hamilton Depressive Scale and the Covi Anxiety Scale, and they completed the Toronto Alexithymia Scale (TAS-20) and the Levels of Emotional Awareness Scale (LEAS). Subjects exhibited low levels of emotional awareness and TAS-20 scores were high. Both measures were not related to depressive and anxious symptomatology. This research is the first to provide LEAS results with substance-dependent patients and highlights their deficits in emotions' differentiation and complexity. The lack of a relationship between LEAS and TAS-20 is discussed from the methodological and theoretical points of view. (c) 2010 Wiley Periodicals, Inc.

Investigating the relationship between subjective drug craving and temporal dynamics of the default mode network, executive control network, and salience network in methamphetamine dependents using rsfMRI

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Soltanian-Zadeh, Somayyeh; Hossein-Zadeh, Gholam-Ali; Shahbabaie, Alireza; Ekhtiari, Hamed

2016-03-01

Resting state functional connectivity (rsFC) studies using fMRI provides a great deal of knowledge on the spatiotemporal organization of the brain. The relationships between and within a number of resting state functional networks, namely the default mode network (DMN), salience network (SN) and executive control network (ECN) have been intensely studied in basic and clinical cognitive neuroscience [1]. However, the presumption of spatial and temporal stationarity has mostly restricted the assessment of rsFC [1]. In this study, sliding window correlation analysis and k-means clustering were exploited to examine the temporal dynamics of rsFC of these three networks in 24 abstinent methamphetamine dependents. Afterwards, using canonical correlation analysis (CCA) the possible relationship between the level of self-reported craving and the temporal dynamics was examined. Results indicate that the rsFC transits between 6 discrete "FC states" in the meth dependents. CCA results show that higher levels of craving are associated with higher probability of transiting from state 4 to 6 (positive FC of DMN-ECN getting weak and negative FC of DMN-SN appearing) and staying in state 4 (positive FC of DMN-ECN), lower probability of staying in state 2 (negative FC of DMN-ECN), transiting from state 4 to 2 (change of positive FC of DMN-ECN to negative FC), and transiting from state 3 to 5 (appearance of negative FC of DMN-SN and positive FC of DMN-ECN with the presence of negative FC of SN-ECN). Quantitative measures of temporal dynamics in large-scale brain networks could bring new added values to increase potentials for applications of rsfMRI in addiction medicine.

Decreased DNA Methylation in the Shati/Nat8l Promoter in Both Patients with Schizophrenia and a Methamphetamine-Induced Murine Model of Schizophrenia-Like Phenotype.

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Kyosuke Uno

Full Text Available The number of patients with schizophrenia has increased over the past decade. Previously, many studies have been performed to establish its diagnostic criteria, prophylactic methods, and effective therapies. In this study, we analyzed whether the ratios of DNA methylation in CpG islands of the Shati/Nat8l is decreased in model mice of schizophrenia-like phenotype using genomic DNA collected from brain regions and peripheral blood, since the mouse model of schizophrenia-like phenotype, mice treated repeatedly with methamphetamine showed increase of Shati/Nat8l mRNA expression in our previous experiment. The ratios of Shati/Nat8l CpG island methylation were significantly decreased in both the nucleus accumbens and the peripheral blood of model mice compared with those of control mice. We also investigated Shati/Nat8l methylation in the blood of patients with schizophrenia. We found that Shati/Nat8l CpG island methylation ratios were lower in the patients with schizophrenia than in the healthy controls, which is consistent with our findings in the mice model. To our knowledge, this is the first study to show similar alterations in methylation status of a particular genomic DNA site in both the brain and peripheral blood of mice. Furthermore, the same phenomenon was observed in corresponding human genomic sequences of the DNA extracted from the peripheral blood of patients with schizophrenia. Based on our findings, DNA methylation profiles of the CpG island of Shati/Nat8l might be a diagnostic biomarker of schizophrenia.

MK-801, but not drugs acting at strychnine-insensitive glycine receptors, attenuate methamphetamine nigrostriatal toxicity.

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Layer, R T; Bland, L R; Skolnick, P

1993-10-15

Repeated administration of methamphetamine (METH) results in damage to nigrostriatal dopaminergic neurons. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists and use-dependent cation channel blockers attenuate METH-induced damage. The objectives of the present study were to examine whether comparable reductions in METH-induced damage could be obtained by compounds acting at strychnine-insensitive glycine receptors on the NMDA receptor complex. Four injections of METH (5 mg/kg i.p.) resulted in a approximately 70.9% depletion of striatal dopamine (DA) and approximately 62.7% depletion of dihydroxyphenylacetic acid (DOPAC) content, respectively. A significant protection against METH-induced DA and DOPAC depletion was afforded by the use-dependent channel blocker, MK-801. The competitive glycine antagonist 7-chlorokynurenic acid (7-Cl-KA), the low efficacy glycine partial agonist (+)-3-amino-1-hydroxy-2-pyrrolidone ((+)-HA-966), and the high efficacy partial glycine agonist 1-aminocyclopropane-carboxylic acid (ACPC) were ineffective against METH-induced toxicity despite their abilities to attenuate glutamate-induced neurotoxicity under both in vivo and in vitro conditions. These results indicate that glycinergic ligands do not possess the same broad neuroprotective spectrum as other classes of NMDA antagonists.

The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice.

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Kesby, James P; Markou, Athina; Semenova, Svetlana

2016-10-01

Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perceived Child Behavior Problems, Parenting Stress, and Maternal Depressive Symptoms among Prenatal Methamphetamine Users

Science.gov (United States)

Liles, Brandi D.; Newman, Elana; LaGasse, Linda L.; Derauf, Chris; Shah, Rizwan; Smith, Lynne M.; Arria, Amelia M.; Huestis, Marilyn A.; Haning, William; Strauss, Arthur; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

2012-01-01

The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months.…

HIV-1, Methamphetamine and Astrocytes at Neuroinflammatory crossroads

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Kathleen eBorgmann

2015-10-01

Full Text Available As a popular psychostimulant, methamphetamine (METH use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10-15% of human immunodeficiency virus-1 (HIV-1 patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND through direct and indirect mechanisms. Repetitive METH use decreases adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression towards AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte number and activity, cytokine signaling, phagocytic function, and CNS infiltration through the blood brain barrier. Further, METH triggers the neuronal dopamine reward pathway and leads to altered neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation. Neuroinflammation modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress and excitotoxicity. Pathologically, glial activation is a hallmark of both HIV-1 and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, neuroinflammation and HAND are carefully reviewed. Interventions targeting astrocytes in HAND and METH are presented as potential novel therapeutic approaches.

Gender Comparisons Among Asian American and Pacific Islander Patients in Drug Dependency Treatment.

Science.gov (United States)

Han, Yun; Lin, Veronique; Wu, Fei; Hser, Yih-Ing

2016-05-11

Few studies have focused on Asian Americans and Pacific Islanders (AAPIs), despite indications of increasing substance abuse among AAPIs in recent years. This prospective longitudinal study examined gender differences among AAPIs in treatment. The study included 567 (177 women, 390 men) AAPI patients drawn from two prior studies, one with 32 community treatment programs in 13 California counties (CalTOP, 3, 9 months), and another project including 36 treatment sites in 5 California counties (TSI, 3, 12 months). Baseline and follow-up assessments utilized the Addiction Severity Index(ASI). A subset of patients was assessed at 3 and 9/12 months (n = 106). Significant gender-related differences were observed at baseline: fewer women than men were employed or never married. More women were living with someone having alcohol and drug problems. Methamphetamine was the primary drug for women and men, followed by alcohol and heroin. Compared to AAPI men, AAPI women reported greater problem severity in family/social relationships (0.18 vs. 0.11, p drug, and legal domains for both genders, and in mental health for men only. Compared to AAPI men, AAPI women demonstrated significantly greater improvements in drug problems (ΔASI = 0.07, p drug use problems for AAPI men.

Active Methamphetamine Use is Associated with Transmitted Drug Resis-tance to Non-Nucleoside Reverse Transcriptase Inhibitors in Individuals with HIV Infection of Unknown Duration

Science.gov (United States)

Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm. Christopher; Smith, Davey M

2007-01-01

Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Design: Cross-sectional analysis. Methods: Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq™, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Results: Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Conclusion: Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI. PMID:18923691

Identification of Novel Signal Transduction, Immune Function, and Oxidative Stress Genes and Pathways by Topiramate for Treatment of Methamphetamine Dependence Based on Secondary Outcomes

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Tianhua Niu

2017-12-01

Full Text Available BackgroundTopiramate (TPM is suggested to be a promising medication for treatment of methamphetamine (METH dependence, but the molecular basis remains to be elucidated.MethodsAmong 140 METH-dependent participants randomly assigned to receive either TPM (N = 69 or placebo (N = 71 in a previously conducted randomized controlled trial, 50 TPM- and 49 placebo-treated participants had a total 212 RNA samples available at baseline, week 8, and week 12 time points. Following our primary analysis of gene expression data, we reanalyzed the microarray expression data based on a latent class analysis of binary secondary outcomes during weeks 1–12 that provided a classification of 21 responders and 31 non-responders with consistent responses at both time points.ResultsBased on secondary outcomes, 1,381, 576, 905, and 711 differentially expressed genes at nominal P values < 0.05 were identified in responders versus non-responders for week 8 TPM, week 8 placebo, week 12 TPM, and week 12 placebo groups, respectively. Among 1,381 genes identified in week 8 TPM responders, 359 genes were identified in both week 8 and week 12 TPM groups, of which 300 genes were exclusively detected in TPM responders. Of them, 32 genes had nominal P values < 5 × 10−3 at either week 8 or week 12 and false discovery rates < 0.15 at both time points with consistent directions of gene expression changes, which include GABARAPL1, GPR155, and IL15RA in GABA receptor signaling that represent direct targets for TPM. Analyses of these 300 genes revealed 7 enriched pathways belonging to neuronal function/synaptic plasticity, signal transduction, inflammation/immune function, and oxidative stress response categories. No pathways were enriched for 72 genes exclusively detected in both week 8 and week 12 placebo groups.ConclusionThis secondary analysis study of gene expression data from a TPM clinical trial not only yielded consistent results with those of primary

Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

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Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

2014-01-01

Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

Does methamphetamine affect bone metabolism?

International Nuclear Information System (INIS)

Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

2014-01-01

There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10 mg/kg METH groups (n = 6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5 mg/kg METH showed an increased locomotor activity, whereas those receiving 10 mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5 mg/kg METH group, but not in the 10 mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5 mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10 mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that

Does methamphetamine affect bone metabolism?

Science.gov (United States)

Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

2014-05-07

There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might

Spontaneous pneumomediastinum: A rare complication of methamphetamine use.

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Albanese, Jessica; Gross, Cole; Azab, Mohamed; Mahalean, Sinziana; Makar, Ranjit

2017-01-01

To present an unusual case of spontaneous pneumomediastinum subsequent to recreational amphetamine use. A young African American adult male was admitted to internal medicine service for treatment of rhabdomyolysis secondary to methamphetamine use. On admission, he was complaining of chest pain in addition to nausea and generalized muscle aches. By his second hospital day, chest pain had resolved yet physical exam demonstrated crepitation of the anterior chest and left axilla. Portable chest x-ray revealed subcutaneous emphysema in addition to pneumomediastinum. Spontaneous pneumomediastinum is a rare complication of amphetamine use that is often associated with subcutaneous emphysema and can be diagnosed with chest x-ray. Management is conservative, with observation, pain control, and supplemental oxygen as needed.

A Vodcasted, Cross-Disciplinary, Behavioral Neuroscience Laboratory Exercise Investigating the Effects of Methamphetamine on Aggression

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Shanks, Ryan A.; Southard, E. Megan; Tarnowski, Laura; Bruster, Matthew; Wingate, Stacia W.; Dalman, Nancy; Lloyd, Steven A.

2011-01-01

This article describes a laboratory experience utilizing videos to engage students in hypothesis-driven experimentation in behavioral neuroscience. It provides students with an opportunity to investigate the effects of chronic methamphetamine exposure on aggression in adult mice using a resident-intruder paradigm. Instructors and students only…

An Investigation of Bioecological Influences Associated with First Use of Methamphetamine in a Rural State

Science.gov (United States)

Bowen, Anne; Moring, John; Williams, Mark; Hopper, Glenna; Daniel, Candice

2012-01-01

Purpose: Methamphetamine (MA) addiction is a significant problem in rural areas of the United States. Yet, little theoretically driven formative research has been conducted on the interactions of factors influencing initiation. The study was guided by Bronfenbrenner's bioecological model. Methods: Eighty-three MA users participated in an…

PSYCHIATRIC COMORBIDITY IN PATIENTS WITH OPIOID DEPENDENCE

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Shihab Kattukulathil

2018-02-01

Full Text Available BACKGROUND Opioid dependence is a major public health problem in Kerala. Presence of psychiatric disorder among opioid dependent patients worsens the scenario. To date no attempts have been made to analyse the magnitude and pattern of comorbid psychiatric disorders in the state. MATERIALS AND METHODS We assessed 30 patients with ICD-10 diagnosis of opioid dependence syndrome for the presence of comorbid psychiatric disorders using structured clinical interview for DSM IV Axis 1 disorder (SCID-1. Patients with opioid withdrawal state, delirium and acute medical emergencies were excluded. RESULTS 56.7% of our subjects had a comorbid psychiatric disorder. Major depressive disorder was the most common one (n=7, 23.3%. Prevalence of other disorders were generalised anxiety disorder (n=6, 20%, bipolar affective disorder (n=3, 10% and schizophrenia (n=1, 3.3%. CONCLUSION Comorbid Psychiatric disorders are highly prevalent in opioid dependence. There is a need for further large sample studies in the areas of comorbidities and in the integrated strategies for the identification and management of both opioid dependence and comorbid psychiatric disorders.

Gas chromatographic/mass spectrometric determination of carbon isotope composition in unpurified samples: methamphetamine example.

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Low, I A; Liu, R H; Legendre, M G; Piotrowski, E G; Furner, R L

1986-10-01

A gas chromatograph/quadrupole mass spectrometer system, operated in electron impact/selected ion monitoring mode, is used to determine the intensity ratio of the m/z 59 and the m/z 58 ions of the [C3H8N]+ fragment derived from methamphetamine samples synthesized with varying amounts of 13C-labeled methylamine. Crude products are introduced into the gas chromatograph without prior cleanup. The ratios measured were in excellent agreement with those calculated. A change in 0.25% use of 13C-methylamine is sufficient for product differentiation. The feasibility of using isotope labeling and subsequent mass spectrometric isotope ratio measurement as the basis of a compound tracing mechanism is discussed. Specifically, if methamphetamine samples manufactured from legal sources are asked to incorporate distinct 13C compositions, their sources can be traced when samples are diverted into illegal channels. Samples derived from illicit preparations can also be traced if the manufacturers of a precursor (methylamine in this case) incorporate distinct 13C compositions in their products.

MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

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Rafael eDe La Torre

2012-11-01

Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

Involvement of free radicals followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: Comparison of the therapeutic potential of fullerene, mepacrine, and cooling

International Nuclear Information System (INIS)

Mori, Tomohisa; Ito, Shinobu; Namiki, Mizuho; Suzuki, Tadashi; Kobayashi, Shizuko; Matsubayashi, Kenji; Sawaguchi, Toshiko

2007-01-01

An increase in polydrug abuse is a major problem worldwide. The coadministration of methamphetamine and morphine increased subacute toxicity or lethality in rodents. However, the underlying mechanisms by which lethality is increased by the coadministration of methamphetamine and morphine are not yet fully understood. Coadministered methamphetamine and morphine induced lethality by more than 80% in BALB/c mice, accompanied by the rupture of cells in the kidney and liver, and an increase in poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine was significantly attenuated by pretreatment with mepacrine (phospholipase A 2 inhibitor) or fullerene (a radical scavenger), or by cooling from 30 to 90 min after drug administration. Furthermore, based on the results of the electron spin resonance spin-trapping technique, hydroxyl radicals were increased by the administration of methamphetamine and morphine, and these increased hydroxyl radicals were potently attenuated by fullerene and cooling. These results suggest that hydroxyl radicals plays an important role in the increased lethality induced by the coadministration of methamphetamine plus morphine. The potency of cooling or drugs for decreasing the subacute toxicity or lethality induced by the coadministration of methamphetamine and morphine was in the order fullerene = cooling > mepacrine. These results indicate that fullerene and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine

Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala.

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Holder, Mary K; Veichweg, Shaun S; Mong, Jessica A

2015-01-01

Methamphetamine (METH) is a psychomotor stimulant strongly associated with increases in sexual drive and impulsive sexual behaviors that often lead to unsafe sexual practices. In women METH users, such practices have been associated with increases in unplanned pregnancies and sexually transmitted diseases. Despite this significant heath concern, the neural mechanisms underlying this drug-sex association are not known. We previously established a rodent model of METH-facilitated female sexual behavior in which estradiol and progesterone interact with METH to increase motivational components of female behavior and neuronal activation in the posterodorsal medial amygdala (MePD) (Holder et al., 2010; Holder and Mong, 2010). The current study more directly examines the mechanisms underlying the drug-sex interaction. Here, we hypothesize that METH-induced increases in MePD dopamine signaling bridge the METH-hormone interaction. In support of this hypothesis, we found that excitotoxic lesions targeted to the MePD attenuated the METH-induced increases in proceptive behavior. Furthermore, infusion of a D1 agonist into the MePD increased proceptive behavior, while infusion of a D1 antagonist blocked the ability of METH to increase proceptive behaviors. Additionally, we found that METH-treatment increased progesterone receptor (PR) immunoreactivity in the MePD, suggesting an interaction between dopamine and progesterone signaling. Indeed, infusions of the PR antagonist, RU486, prevented METH-induced increases in sexual behavior. Thus, taken together, the current findings suggest that dopamine in the MePD modulates enhanced sexual motivation via an amplification of progesterone signaling and contributes to a better understanding of the neurobiology of drug-enhanced sexual behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex-dependent modification by chronic caffeine of acute methamphetamine effects on anxiety-related behavior in rats.

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Hughes, Robert N; Hamilton, Jennifer J

2018-06-01

For fourteen days, male and female PVG/c hooded rats were provided continuously with either pure drinking water, or water containing caffeine in a quantity approximating a daily dose of 31.1 mg/kg. Then at intervals of 3 days, they were administered 1, 2 mg/kg methamphetamine (MA) or saline before being tested for anxiety-related behavior in a zero maze or a light/dark box, or their short-term spatial memory was assessed in a Y maze following introduction of a novel brightness change in one of the arms. Each rat experienced each type of apparatus with the same acute MA or saline treatment while still exposed to chronic caffeine or pure drinking water. While chronic caffeine on its own did not affect any behavioral measure, acute MA was anxiolytic for male rats suggested by increased entries and occupancy of zero-maze enclosed areas, and decreased emergence latencies and increased entries into the light/dark-box light compartment. Females were less affected than males by MA in both types of apparatus unless they also consumed caffeine. For male rats, choices of the Y-maze novel arm were affected by neither caffeine nor MA, but for females provided with unadulterated water, such choices were reduced by 1 mg/kg MA but increased for those exposed to caffeine, thereby suggesting either impaired or improved memory respectively. However, changes in anxiety could also explain these results. Overall, results generated in the three types of apparatus supported potentiation by caffeine of any effects of MA on anxiety for females only. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular bases of methamphetamine-induced neurodegeneration.

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Cadet, Jean Lud; Krasnova, Irina N

2009-01-01

Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. The addiction to METH is a major public concern because its chronic abuse is associated with serious health complications including deficits in attention, memory, and executive functions in humans. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. Thus, the purpose of the present paper is to review cellular and molecular mechanisms that might be responsible for METH neurotoxicity. These include oxidative stress, activation of transcription factors, DNA damage, excitotoxicity, blood-brain barrier breakdown, microglial activation, and various apoptotic pathways. Several approaches that allow protection against METH-induced neurotoxic effects are also discussed. Better understanding of the cellular and molecular mechanisms involved in METH toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of psychostimulant use disorders in humans.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

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R.C.S Martins

2008-01-01

Full Text Available Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip, methamphetamine (7 mg/kg, ip, or modafinil (100 mg/kg, ip subsequent to paradoxical sleep deprivation (PSD for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01. Regarding slow wave sleep (SWS, rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05. In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05. Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.

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Young, Erica J; Aceti, Massimiliano; Griggs, Erica M; Fuchs, Rita A; Zigmond, Zachary; Rumbaugh, Gavin; Miller, Courtney A

2014-01-15

Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown. Conditioned place preference (n = 112) and context-induced reinstatement of self-administration (n = 19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity. Memories formed through association with METH but not associations with foot shock or food reward were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the postconsolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent, and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory. Thus, drug-associated memories seem to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges.

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Hodges, A B; Ladenheim, B; McCoy, M T; Beauvais, G; Cai, N; Krasnova, I N; Cadet, J L

2011-03-01

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH -induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems.

Effect of the acquisition enhancing drug piracetam on rat cerebral energy metabolism. Comparison with naftidrofuryl and methamphetamine

NARCIS (Netherlands)

Nickolson, V.J.; Wolthuis, O.L.

1976-01-01

The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both

A Role for D1 Dopamine Receptors in Striatal Methamphetamine-Induced Neurotoxicity

OpenAIRE

Friend, Danielle M.; Keefe, Kristen A.

2013-01-01

Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 Dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Import...

Methamphetamine induces apoptosis in immortalized neural cells: protection by the proto-oncogene, bcl-2.

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Cadet, J L; Ordonez, S V; Ordonez, J V

1997-02-01

Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.

Prevalence of Demodex spp among alcohol-dependent patients

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Mehmet Hanifi Kokacya

2016-06-01

Conclusion: Demodex spp. are more common in alcohol-dependent patients due conditions of reduced self-care and immunosuppression. Demodex parasites should be considered in alcohol-dependent patients with skin lesions, especially on the face, and should to be treated if needed. [Cukurova Med J 2016; 41(2.000: 259-263

Demoralization in Opioid Dependent Patients: A Comparative Study with Cancer Patients and Community Subjects

NARCIS (Netherlands)

Jong, C.A.J. de; Kissane, D.W.; Geessink, R.J.; Velden, D. van der

2008-01-01

Aim: To study existential distress or demoralization expressed as meaninglessness and helplessness in opioid dependent patients. xxx Method: Comparison of existential distress between opioid dependent patients (n=131), patients with advanced cancer (n=100) and a community based sample without severe

Overview of long non-coding RNA and mRNA expression in response to methamphetamine treatment in vitro

NARCIS (Netherlands)

Xiong, Kun; Long, Lingling; Zhang, Xudong; Qu, Hongke; Deng, Haixiao; Ding, Yanjun; Cai, Jifeng; Wang, Shuchao; Wang, Mi; Liao, Lvshuang; Huang, Jufang; Yi, Chun-Xia; Yan, Jie

2017-01-01

Long non-coding RNAs (IncRNAs) display multiple functions including regulation of neuronal injury. However, their impact in methamphetamine (METH)-induced neurotoxicity has rarely been reported. Here, using microarray analysis, we investigated the expression profiling of lncRNAs and mRNAs in primary

Methamphetamine Use and Sexual Risk Behavior among High School Students in Cape Town, South Africa

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Pluddemann, Andreas; Flisher, Alan J.; McKetin, Rebecca; Parry, Charles D.; Lombard, Carl J.

2012-01-01

Objective: To investigate whether methamphetamine use is associated with sexual risk behavior among adolescents. Method: A cross-sectional survey of 1,561 male and female high school students in Cape Town (mean age 14.9 years) was conducted using items from the Problem Oriented Screening Instrument for Teenagers (POSIT) HIV Risk Scale. Results:…

Meth mouth severity in response to drug-use patterns and dental access in methamphetamine users.

Science.gov (United States)

Brown, Ronni E; Morisky, Donald E; Silverstein, Steven J

2013-06-01

Meth mouth is the rapid development of tooth decay in methamphetamine users. Our study questioned whether drug-use patterns and dental care access are risk factors affecting the severity of meth mouth. Participants received dental examinations, and the number of decayed, missing and filled teeth (DMFT) were counted and used to measure meth mouth severity.

The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

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Fialová, Markéta; Šírová, Jana; Bubeníková-Valešová, Věra; Šlamberová, Romana

2015-01-01

The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

Impact of methamphetamine on infection and immunity

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Sergio A Salamanca

2015-01-01

Full Text Available The prevalence of methamphetamine (METH use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation.

Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

Science.gov (United States)

Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

2018-02-28

Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L→DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L→DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT→DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L→DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L→DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L→DMS glutamatergic projections in incubation of drug craving and drug seeking. SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of

Prevalence and Correlates of Heroin-Methamphetamine Co-Injection Among Persons Who Inject Drugs in San Diego, California, and Tijuana, Baja California, Mexico.

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Meacham, Meredith C; Strathdee, Steffanie A; Rangel, Gudelia; Armenta, Richard F; Gaines, Tommi L; Garfein, Richard S

2016-09-01

Although persons who inject drugs (PWID) in the western United States-Mexico border region are known to inject both heroin and methamphetamine, little is known about the prevalence and risks associated with co-injection of this depressant-stimulant combination (also known as "goofball" and "Mexican speedball"). Baseline data from parallel cohort studies of PWID conducted concurrently in San Diego, CA, and Tijuana, Mexico, were used to estimate the prevalence and identify correlates of heroin-methamphetamine co-injection. PWID older than 18 years of age who reported injecting illicit drugs in the past month (N = 1,311; 32.7% female) were recruited in San Diego (n = 576) and Tijuana (n = 735) and completed interviewer-administered questionnaires. Bivariate and multivariable logistic regression analyses were used to identify correlates of heroin-meth-amphetamine co-injection. The prevalence of co-injection in the past 6 months was 39.9% overall and was higher in Tijuana (55.8%) than in San Diego (19.8%). In multivariable analyses adjusting for study cohort, distributive syringe sharing, purchasing syringes prefilled with drugs, finding it hard to get new syringes, reporting great or urgent need for treatment, and younger age were independently associated with co-injection. Past-6-month overdose was significantly associated with higher odds of co-injection in San Diego than in Tijuana. These findings indicate that heroin-methamphetamine co-injection is more common in Tijuana than in San Diego, yet this practice was only associated with overdose in San Diego. Heroin-methamphetamine coinjection was also independently associated with HIV-associated injection risk behaviors. Overdose-prevention interventions should address co-injection of depressants and stimulants.

A community-engaged randomized controlled trial of an integrative intervention with HIV-positive, methamphetamine-using men who have sex with men

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Adam W. Carrico

2016-07-01

Full Text Available Abstract Background Contingency management (CM is an evidence-based intervention providing tangible rewards as positive reinforcement for abstinence from stimulants such as methamphetamine. Integrative approaches targeting affect regulation could boost the effectiveness of CM in community-based settings and optimize HIV/AIDS prevention efforts. Methods/Design This randomized controlled trial with HIV-positive, methamphetamine-using men who have sex with men (MSM is examining the efficacy of a 5-session, individually delivered positive affect regulation intervention – Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS. ARTEMIS is designed to sensitize individuals to non-drug-related sources of reward as well as assist with managing depression and other symptoms of stimulant withdrawal during CM. HIV-positive, methamphetamine-using MSM who are enrolled in a community-based, 12-week CM program are randomized to receive ARTEMIS or an attention-matched control condition. Follow-up assessments are conducted at 3, 6, 12, and 15 months after enrollment in CM. Four peripheral venous blood samples are collected over the 15-month follow-up with specimen banking for planned biomarker sub-studies. The primary outcome is mean HIV viral load. Secondary outcomes include: sustained HIV viral suppression, T-helper cell count, psychological adjustment, stimulant use, and potentially amplified transmission risk behavior. Discussion Implementation of this randomized controlled trial highlights the importance of delineating boundaries between research activities and community-based service provision. It also provides insights into best practices for integrating the distinct agendas of academic and community partners in clinical research. This trial is currently enrolling and data collection is anticipated to be completed in September of 2018. Trial registration This trial was registered on clinicaltrials.gov ( NCT01926184 on

Acute effects of heroin on emotions in heroin-dependent patients.

Science.gov (United States)

Blum, Julia; Gerber, Hana; Gerhard, Urs; Schmid, Otto; Petitjean, Sylvie; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Borgwardt, Stefan J; Walter, Marc

2013-01-01

Euphoria has been described in heroin-dependent individuals after heroin administration. However, affective disturbances and disorders are common in heroin dependence. The present study examined the acute effects of heroin on emotions in heroin-dependent patients. This randomized controlled crossover trial included 28 heroin-dependent patients (67.9% male, n = 19) in stable heroin-assisted treatment and 20 healthy controls. The patients were administered heroin or saline (placebo), the controls were administered saline. Data measuring mood, affects and heroin craving (BDI, AMRS, STAI, STAXI, and HCQ) were assessed before and 60 minutes after substance injection. Before substance injection, heroin-dependent patients showed significantly higher levels of anxiety and depression than healthy controls (p emotions, including craving, and a significant increase in emotional well-being (p emotions, once they had received heroin. Heroin dampens craving, negative emotions, and increases positive emotions. These findings indicate that heroin regulates emotions and underscore the clinical benefit of opioid substitution treatment for heroin-dependent patients. Copyright © American Academy of Addiction Psychiatry.

Age-Related Differences in NMDA Receptor Subunits of Prenatally Methamphetamine-Exposed Male Rats

Czech Academy of Sciences Publication Activity Database

Vrajová, M.; Schutová, B.; Klaschka, Jan; Štěpánková, H.; Řípová, D.; Šlamberová, R.

2014-01-01

Roč. 39, č. 11 (2014), s. 2040-2046 ISSN 0364-3190 Grant - others:GA ČR(CZ) GAP303/10/0580; Ministerstvo školství(CZ) CSM 7/CRP/2014; Univerzita Karlova(CZ) Prvouk P34; Univerzita Karlova(CZ) 260045/SVV/2014; Prague Psychiatric Center(CZ) MH CZ–DRO: 00023752 Institutional support: RVO:67985807 Keywords : methamphetamine * in-utero * NMDA receptor subunits * hippocampus Subject RIV: FH - Neurology Impact factor: 2.593, year: 2014

COMORBIDITY DIAGNOSES IN ALCOHOL DEPENDENT PATIENTS: DIFFERENCES AND DILEMMAS

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Maja Rus-Makovec

2002-11-01

Full Text Available Background. In the presented study we followed the diagnostic procedures of comorbidity in alcohol dependent patients of in-patient treatment. The aim of the study was to evaluate the incidence of dual/triple diagnoses with alcohol dependent patients and to incorporate the diagnostic procedures in rutine work and in treatment planning.Material and methods. We were following the basic parameters of treatment of 469 patients (366 male, 102 female from July 1999 to July 2001. The diagnostic criteria according to ICD-10 were applied after at least four weeks of sobriety.Results. The most frequent additional diagnoses found were nicotine dependency, depressive and personal disorders. Main gender differences were found in diagnosis of depressive disorders and in dependency or abuse of prescripted drugs. Comparison of our results with literature data showed the greatest differences in diagnoses of cognitive, depressive, anxious data and dependency of other psychoactive substances.Conclusions. The comparison between the two time periods shows that stuff sensibility to diagnostic procedures of comorbidity states influences the frequency of diagnostic categories. The literature data review leads to impression of inconsistent diagnosing regarding the context and phylosophy of treatment context, stuff education and patient population.

ORAL IBOPAMINE SUBSTITUTION IN PATIENTS WITH INTRAVENOUS DOPAMINE DEPENDENCE

NARCIS (Netherlands)

GIRBES, ARJ; MILNER, AR; MCCLOSKEY, BV; ZWAVELING, JH; VANVELDHUISEN, DJ; ZIJLSTRA, JG; LIE, KI

1995-01-01

In a prospective open study we evaluated whether intravenous dopamine infusions can be safely switched to enterally administered ibopamine in dopamine-dependent patients. Six patients defined as being clinically stable, normovolaemic, but dopamine dependent, i.e. with repeated inability to stop

[Motivational interviewing with alcohol-dependent patients].

Science.gov (United States)

Spaeth, Michael; Bleich, Stefan; Hillemacher, Thomas

2017-09-01

Motivational interviewing with alcohol-dependent patients Alcohol-dependent patients do not need to be motivated from the outside. They are mostly ambivalent, and the inner voice, which already speaks for change (change talk), is heard through motivational interviewing, carefully strengthened and developed together with the patient. The practitioner has to deal with the human spirit of motivational interviewing and should be able to communicate with empathy, respect, congruence, and openness. The patient's autonomy should always be maintained. Advice is only given upon request. The conversation style is directive-guiding instead of authoritariansteering. OARS and the EPE principle are the motivational interviewing basics, which are consistently applied over 4 processes of motivational interviewing: engaging, focusing, evocing, and planning. The likelihood of change talk increases as soon as discrepancies between life goals and alcohol consumption emerge. An increased rate of change talk makes a change in behavior more likely. If a patient argues against change (sustain talk), one should not confront, but should consistently work with reflections, reframing, and an emphasis on autonomy. Motivational interviewing can be applied in different settings and populations, should be learned by the entire team (best professional guidance) in teamwork, and be subjected to a critical and constant evaluation. Georg Thieme Verlag KG Stuttgart · New York.

Dynamic surface-enhanced Raman spectroscopy and Chemometric methods for fast detection and intelligent identification of methamphetamine and 3, 4-Methylenedioxy methamphetamine in human urine

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Weng, Shizhuang; Dong, Ronglu; Zhu, Zede; Zhang, Dongyan; Zhao, Jinling; Huang, Linsheng; Liang, Dong

2018-01-01

Conventional Surface-Enhanced Raman Spectroscopy (SERS) for fast detection of drugs in urine on the portable Raman spectrometer remains challenges because of low sensitivity and unreliable Raman signal, and spectra process with manual intervention. Here, we develop a novel detection method of drugs in urine using chemometric methods and dynamic SERS (D-SERS) with mPEG-SH coated gold nanorods (GNRs). D-SERS combined with the uniform GNRs can obtain giant enhancement, and the signal is also of high reproducibility. On the basis of the above advantages, we obtained the spectra of urine, urine with methamphetamine (MAMP), urine with 3, 4-Methylenedioxy Methamphetamine (MDMA) using D-SERS. Simultaneously, some chemometric methods were introduced for the intelligent and automatic analysis of spectra. Firstly, the spectra at the critical state were selected through using K-means. Then, the spectra were proposed by random forest (RF) with feature selection and principal component analysis (PCA) to develop the recognition model. And the identification accuracy of model were 100%, 98.7% and 96.7%, respectively. To validate the effect in practical issue further, the drug abusers'urine samples with 0.4, 3, 30 ppm MAMP were detected using D-SERS and identified by the classification model. The high recognition accuracy of > 92.0% can meet the demand of practical application. Additionally, the parameter optimization of RF classification model was simple. Compared with the general laboratory method, the detection process of urine's spectra using D-SERS only need 2 mins and 2 μL samples volume, and the identification of spectra based on chemometric methods can be finish in seconds. It is verified that the proposed approach can provide the accurate, convenient and rapid detection of drugs in urine.

Pentazocine dependence among sickle cell disease patients ...

African Journals Online (AJOL)

Introduction: Sickle cell disease is a chronic disease. Severe bone pain is commonly the hallmark of clinical features. This commonly necessitates the use of analgesics especially Opioids which unfortunately have a high potential to produce dependence. The complications of dependence in patients on any psychoactive ...

[Studies on origin of illicit methamphetamine. I. The relationship of enantiomeric compositions between methamphetamine and its raw material (ephedrine)].

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Kikura, R; Shimamine, M; Nakahara, Y; Terao, T

1992-01-01

In order to elucidate the relationship of enantiomeric compositions between methamphetamine (MA) and its raw materials, ephedrine (EP) enantiomers, commercial EP samples and MA samples prepared from them were analyzed by HPLC using GITC-prelabeling. The GITC derivatives were separated on ODS column using methanol-water-acetic acid (45:54:1) at a flow rate of 1.2 ml/min for EP and tetrahydrofuran-water-acetic acid (29:70:1) at a flow rate of 1 ml/min for MA. The chromatographic conditions resulted in such a good separation of four EP and two MA enantiomers that 1/1000 enantiomeric impurities could be detected and discriminated from the major enantiomer with good reproducibility. Moreover, it was demonstrated that the asymmetric center at alpha-position of amino group was entirely retained throughout the reductive reaction of the EP samples, and that the MA samples inherited the enantiomeric character from the EP samples used. This method was applied to discriminative analysis of MA samples seized in Japan.

Cohort study of HIV-positive and -negative methamphetamine users.

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Spolsky, Vladimir W; Clague, Jason; Shetty, Vivek

2018-04-20

The effects of methamphetamine (MA) on caries have been well documented. Little, however, is known about its effects on the periodontium. The authors conducted this study to determine the prevalence and severity of periodontal disease in an urban population of HIV-positive MA users. This cross-sectional survey was conducted in one of the most populous urban areas of Los Angeles County, California, beset with high rates of MA use. Participants were recruited by a combination of street outreach methods, referral from drug treatment centers, and word of mouth. Participants were eligible if they were older than 18 years, spoke English or Spanish, used MA in the past 30 days, were willing to undergo a dental examination and psychosocial assessments, and were willing to provide a urine sample. Periodontal assessments were completed for 541 participants by 3 trained and calibrated dentists. The prevalence and severity of periodontal disease were high in this population of HIV-positive and -negative MA users. Cigarette smoking and age were identified as risk factors. The HIV-positive and -negative cohorts were remarkably similar, suggesting that their lifestyles contributed more to their destructive periodontal disease than their MA use. MA users are at high risk of developing destructive periodontal disease and badly broken-down teeth. Clinicians should plan accordingly for timely management of the patients' care, knowing that MA users have extensive periodontal and restorative treatment needs. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Recruitment Strategies of Methamphetamine-Using Men Who Have Sex with Men into an Online Survey.

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Wilkerson, J Michael; Shenk, Jared E; Grey, Jeremy A; Simon Rosser, B R; Noor, Syed W

Recruiting hidden populations into online research remains challenging. In this manuscript, we report lessons learned from our efforts to recruit methamphetamine-using men who have sex with men. Between July and October 2012, we implemented a four-phase recruitment strategy to enroll a total of 343 methamphetamine-using MSM into an online survey about recent substance use, sexual behavior, and various psychosocial measures. The four phases were implemented sequentially. During phase one, we placed advertisements on mobile applications, and during phase two, we placed advertisements on traditional websites formatted for browsers. During phase three, we used e-mail to initiate snowball recruitment, and during phase four, we used social media for snowball recruitment. Advertisements on mobile devices and websites formatted for browsers proved to be expensive options and resulted in few eligible participants. Our attempts to initiate a snowball through e-mail also proved unsuccessful. The majority (n=320) of observations in our final dataset came from our use of social media. However, participant fraud was a concern, requiring us to implement a strong participant verification protocol. For maximum recruitment and cost-effectiveness, researchers should use social media for recruitment provided they employ strong participant verification protocols.

Carbon coated magnetic nanoparticles as a novel magnetic solid phase extraction adsorbent for simultaneous extraction of methamphetamine and ephedrine from urine samples.

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Taghvimi, Arezou; Hamishehkar, Hamed

2017-01-15

This paper develops a highly selective, specific and efficient method for simultaneous determination of ephedrine and methamphetamine by a new carbon coated magnetic nanoparticles (C/MNPs) as a magnetic solid phase extraction (MSPE) adsorbent in biological urine medium. The characterization of synthesized magnetic nano adsorbent was completely carried out by various characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, powder x-ray diffraction (XRD), scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM). Nine important parameters influencing extraction efficiency including amount of adsorbent, amounts of sample volume, pH, type and amount of extraction organic solvent, time of extraction and desorption, agitation rate and ionic strength of extraction medium, were studied and optimized. Under optimized extraction conditions, a good linearity was observed in the concentration range of 100-2000ng/mL for ephedrine and 100-2500ng/mL for methamphetamine. Analysis of positive urine samples was carried out by proposed method with the recovery of 98.71 and 97.87% for ephedrine and methamphetamine, respectively. The results indicated that carbon coated magnetic nanoparticles could be applied in clinical and forensic laboratories for simultaneous determination of abused drugs in urine media. Copyright © 2016 Elsevier B.V. All rights reserved.

Partner dependence and sexual risk behavior among STI clinic patients.

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Senn, Theresa E; Carey, Michael P; Vanable, Peter A; Coury-Doniger, Patricia

2010-01-01

To investigate the relation between partner dependence and sexual risk behavior in the context of the information-motivation-behavioral skills (IMB) model. STI clinic patients (n = 1432) completed a computerized interview assessing partner dependence, condom use, and IMB variables. Men had higher partner-dependence scores than women did. Patients reporting greater dependence reported less condom use. Gender did not moderate the partner dependence-condom-use relationship. Partner dependence did not moderate the relation between IMB constructs and condom use. Further research is needed to determine how partner dependence can be incorporated into conceptual models of safer sex behaviors.

Marital adjustment of patients with substance dependence, schizophrenia and bipolar affective disorder

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Shital S Muke

2014-01-01

Full Text Available Background: Marital adjustment is considered as a part of social well-being. Disturbed marital relationship can directly affect the disease adjustment and the way they face disease outcomes and complications. It may adversely affect physical health, mental health, the quality-of-life and even economic status of individuals. Aim: The aim of this study was to compare the marital adjustment among patients with substance dependence, schizophrenia and bipolar affective disorder. Materials and Methods: The sample consisted of each 30 patients with substance dependence, bipolar affective disorder and schizophrenia, diagnosed as per international classification of diseases-10 diagnostic criteria for research with a minimum duration of illness of 1 year were evaluated using marital adjustment questionnaire. The data was analyzed using parametric and non-parametric statistics. Results: Prevalence of poor marital adjustment in patients with schizophrenia, bipolar affective disorder and substance dependence was 60%, 70% and 50% respectively. There was a significant difference on overall marital adjustment among substance dependence and bipolar affective disorder patients. There was no significant difference on overall marital adjustment among patients with substance dependence and schizophrenia as well as among patients with schizophrenia and bipolar affective disorder. On marital adjustment domains, schizophrenia patients had significantly poor sexual adjustment than substance dependence patients while bipolar affective disorder patients had significantly poor sexual and social adjustment compared with substance dependence patients. Conclusion: Patients with substance dependence have significant better overall marital adjustment compared with bipolar affective disorder patients. Patients with substance dependence have significantly better social and sexual adjustment than patients with bipolar affective disorder as well as significantly better sexual

Methamphetamine and amphetamine concentrations in survivors of body-packer syndrome in Japan.

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Uekusa, Kyoko; Hayashida, Makiko; Saito, Nobuyuki; Mashiko, Kunihiro; Hara, Kenji; Waters, Brian; Ohno, Youkichi

2013-04-10

There are few reports from Japan on the analysis of fluids in survivors of body-packer syndrome. We analyzed the concentrations of stimulants in the serum, plasma and urine collected from three patients suspected of being body packers at immigration that were referred to hospitals between 2010 and 2011. The drugs were extracted with solid-phase columns and analyzed by gas chromatography-mass spectrometry (GC-MS). In all cases, wrapped, cylindrical packets of foreign bodies were detected in the intestinal tract on plain X-ray (X-P) and computed tomography (CT), and they were eventually removed surgically. In case 1, the patient presented with convulsions and tachycardia at admission to the hospital and one of the packets was found to have ruptured. In case 2, although the subject appeared to have an intestinal obstruction caused by the packets on the third day, he exhibited no symptoms on arrival and the packets did not appear to have ruptured. In case 3, the patient exhibited restlessness on the first day and one of the removed packets had ruptured. In all cases, methamphetamine (MA) and amphetamine (AP) were detected in serum, plasma and urine. In this study, we report the variation in MA and AP concentrations in survivors of body-packer syndrome. The serum and plasma concentrations of MA were high in subjects that exhibited symptoms of MA intoxication. MA and AP were also detected in the case in which the patient exhibited no symptoms of intoxication and the packets had not ruptured. These results suggest either that the stimulants may have seeped through the wrap of the packets, or that the subject had been abusing the drugs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk

Czech Academy of Sciences Publication Activity Database

Rambousek, Lukáš; Kačer, P.; Syslová, K.; Bumba, J.; Bubeníková-Valešová, V.; Šlamberová, R.

2014-01-01

Roč. 139, JUN (2014), s. 138-144 ISSN 0376-8716 Institutional support: RVO:67985823 Keywords : methamphetamine * amphetamine * pharmacokinetics * sex differences * breast feeding milk * mass spectrometry Subject RIV: FH - Neurology Impact factor: 3.423, year: 2014

Treating iron overload in patients with non-transfusion-dependent thalassemia

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Taher, Ali T; Viprakasit, Vip; Musallam, Khaled M; Cappellini, M Domenica

2013-01-01

Despite receiving no or only occasional blood transfusions, patients with non-transfusion-dependent thalassemia (NTDT) have increased intestinal iron absorption and can accumulate iron to levels comparable with transfusion-dependent patients. This iron accumulation occurs more slowly in NTDT patients compared to transfusion-dependent thalassemia patients, and complications do not arise until later in life. It remains crucial for these patients' health to monitor and appropriately treat their iron burden. Based on recent data, including a randomized clinical trial on iron chelation in NTDT, a simple iron chelation treatment algorithm is presented to assist physicians with monitoring iron burden and initiating chelation therapy in this group of patients. Am. J. Hematol. 88:409–415, 2013. © 2013 Wiley Periodicals, Inc. PMID:23475638

Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation patterns induced by the common gamma-chain cytokine system

Directory of Open Access Journals (Sweden)

Nikki eBortell

2015-09-01

Full Text Available One factor in the development of neuroAIDS is the increase in the migration of pro-inflammatory CD8 T cells across the Blood Brain Barrier. Typically these cells are involved with keeping the viral load down. However, the persistence of above average numbers of CD8 T cells in the brain, not necessarily specific to viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma chain (γc cytokines. Here, using the non-human primate model of neuroAIDS, we have demonstrated that exposure to Methamphetamine, a powerful illicit drug that has been associated with HIV exposure and neuroAIDS severity, can cause an increase in molecules of the γc system. Among these molecules, IL15, which is upregulated in astrocytes by Methamphetamine, and that induces the proliferation of T cells, may also be involved in driving an inflammatory phenotype in innate immune cells of the brain. Therefore, Methamphetamine and IL15 may be critical in the development and aggravation of Central Nervous System immune-mediated inflammatory pathology in HIV-infected drug abusers.

The Effect of Group Therapy With Transactional Analysis Approach on Emotional Intelligence, Executive Functions and Drug Dependency.

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Forghani, Masoomeh; Ghanbari Hashem Abadi, Bahram Ali

2016-06-01

The aim of the present study was to evaluate the effect of group psychotherapy with transactional analysis (TA) approach on emotional intelligence (EI), executive functions and substance dependency among drug-addicts at rehabilitation centers in Mashhad city, Iran, in 2013. In this quasi-experimental study with pretest, posttest, case- control stages, 30 patients were selected from a rehabilitation center and randomly divided into two groups. The case group received 12 sessions of group psychotherapy with transactional analysis approach. Then the effects of independent variable (group psychotherapy with TA approach) on EI, executive function and drug dependency were assessed. The Bar-on test was used for EI, Stroop test for measuring executive function and morphine test, meth-amphetamines and B2 test for evaluating drug dependency. Data were analyzed using multifactorial covariance analysis, Levenes' analysis, MANCOVA, t-student and Pearson correlation coefficient tests t with SPSS software. Our results showed that group psychotherapy with the TA approach was effective in improving EI, executive functions and decreasing drug dependency (P addicts and prevents addiction recurrence by improving the coping capabilities and some mental functions of the subjects. However, there are some limitations regarding this study including follow-up duration and sample size.

Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice.

OpenAIRE

Mendieta L; Granado, Noelia; Aguilera, J.; Tizabi Y; Moratalla, Rosario