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Sample records for 42-year-old male methamphetamine

  1. Inflammatory cap polyposis in a 42-year-old male

    PubMed Central

    Mason, Meredith; Faizi, Syed Adeel; Fischer, Edgar; Rajput, Ashwani

    2013-01-01

    INTRODUCTION Inflammatory cap polyposis (CP) is an uncommon, non-malignant condition whose pathogenesis is poorly understood. Initial presentation of CP may mimic other gastrointestinal conditions like inflammatory bowel disease, pseudomembranous colitis, irritable bowel syndrome, and colon cancer. PRESENTATION OF CASE A 42-year-old male presented with symptoms of constipation, abdominal pain and weight loss, which were suggestive of a malignancy. DISCUSSION Since the symptoms of CP resemble closely those of other gastrointestinal diseases, particularly colon cancer, making the initial diagnosis can be challenging and it is often delayed. The mainstay of initial treatment is conservative, however symptomatic and complicated cases require prompt surgical intervention with close clinical follow-up. CONCLUSION We chose to report this case because it represents a rare and unique disease process that may masquerade as a colon cancer. It is important for surgeons to be aware of this non-malignant condition since inadequate surgery usually results in recurrence. PMID:23416507

  2. Erasmus Syndrome in a 42-Year-Old Male: A Rare Case Report

    PubMed Central

    Pan, Koushik

    2015-01-01

    Erasmus syndrome is a rare entity in which systemic sclerosis develops following exposure to silica with or without silicosis. Few case reports are available in literature. We report here a case of Erasmus syndrome in a 42-year-old manual labourer. The patient presented with arthralgia, Raynoud’s phenomenon, skin tightening and microstomia along with features of Interstitial Lung Disease (ILD) and pulmonary arterial hypertension. Evidence of Interstitial Lung Disease (ILD) with mediastinal lymphadenopathy as well as pulmonary arterial hypertension with vascular reactivity was found in appropriate investigations. Serological markers of systemic sclerosis were strongly positive. After a diagnosis of Erasmus syndrome was made, a combination of drugs including Prednisone, Cyclophosphamide and Nifedipine was instituted this led to moderate improvement in his symptoms over 6 months. PMID:26155508

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

    PubMed

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

    2016-02-01

    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 amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

  4. Methamphetamine

    MedlinePlus

    ... DEA Press Room » Multi-Media Library » Image Gallery » Methamphetamine METHAMPHETAMINE To Save Images: First click on the thumbnail ... Save in directory and then click Save. Ice Methamphetamine Pipe Ice Methamphetamine Bag Desoxyn Gradumet 5mg Desoxyn ...

  5. A 42-Year-Old Woman With Abnormal Chest CT Scan and Chylous Ascites.

    PubMed

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Yadav, Ruchi; Arrossi, Andrea V; Mehta, Atul C; Faress, Jihane A

    2016-01-01

    A 42-year-old white woman presented to the pulmonary clinic for evaluation of abnormal chest imaging. Twenty years prior to presentation, she was noted to have an abnormal chest radiograph during a routine preemployment evaluation. A subsequent bronchoscopy was nondiagnostic. She was followed up with annual imaging, which demonstrated little or no progression of her disease. She remained symptom free throughout this period. A year before her visit to the pulmonary clinic, she developed abdominal discomfort and was found to have ascites. Subsequently, she underwent three paracenteses with analysis revealing chylous fluid. She was a nonsmoker without a history of exposures or travel. PMID:26757302

  6. Methamphetamine

    MedlinePlus

    Methamphetamine is used as part of a treatment program to control symptoms of attention deficit hyperactivity disorder ( ... people who are the same age) in children. Methamphetamine is also used for a limited period of ...

  7. Methamphetamine

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ...

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

    PubMed

    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. PMID:27232669

  9. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Bui, Albert D; Sprague, Lisanne; D'Souza, Manoranjan S

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. PMID:26683901

  10. Methamphetamine

    MedlinePlus

    Methamphetamine - meth for short - is a very addictive stimulant drug. It is a powder that can be made into ... injected into your body with a needle. Crystal meth is smoked in a small glass pipe. Meth ...

  11. Methamphetamine

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... effects as those of other stimulants, such as cocaine or amphetamines. These include increased wakefulness, increased physical ...

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

    PubMed

    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. PMID:26965573

  13. Amphetamine-related myocardial infarction in a 42-year old man.

    PubMed

    Smędra, A; Szustowski, S; Berent, J

    2015-01-01

    Myocardial infarction is an infrequent condition in young adults. In most cases, it occurs due to causes other than atherosclerosis of the coronary arteries, including blood hypercoagulability, congenital anomalies of the coronary arteries, their inflammation or spasm induced by amphetamine or cocaine use. Amphetamine and its derivatives, via increasing the levels of epinephrine, serotonin and dopamine in the central nervous system, exert their effect also on the cardiovascular system, causing coronary spasm, enhancing platelet aggregation and inducing tachyarrhythmias. The paper presents a case of a 42-year-old man admitted to the emergency department because of emaciation and dehydration. The man was conscious, without contact, with a significant elevation of body temperature and tachycardia. On the basis of examinations, a fresh infarction of the anterolateral wall of the heart was diagnosed and the patient was transferred to a cardiac intensive care unit. There, laboratory tests revealed significantly elevated markers of myocardial necrosis and the presence of amphetamine in blood and urine. In spite of the institution of treatment the patient developed cardiorespiratory arrest. Advanced resuscitation procedures were undertaken, however, they proved unsuccessful. The presence of an infarction focus was confirmed in autopsy. Toxicological analysis of the blood for the presence of alcohol-like substances detected amphetamine at a concentration of 269.5 ng/ml. After examining the complete body of evidence it was established that the patient had died of acute cardiorespiratory failure secondary to an extensive fresh myocardial infarction. As indicated by the accumulated data, the most probable cause of myocardial infarction was amphetamine poisoning. PMID:27003867

  14. Isolated infrarenal abdominal aorta aneurysm in a 42-year-old patient with Marfan’s syndrome: Case report

    PubMed Central

    Hajji, Rita; Zrihni, Youssef; Zaghloul, Rachid; Zizi, Othman; Bouarhroum, Abdellatif

    2013-01-01

    Marfan’s syndrome is an autosomal dominant disorder of connective tissue characterized by a large number of possible mutations and by heterogeneity of clinical presentation primarily in skeletal, ocular and cardiovascular organ systems. Cardiovascular complications of the disease are responsible for high mortality. The case of a 42-year-old patient with a progressive advanced abdominal aorta dilatation visualized on computed tomography images is presented. Pathogenesis, diagnosis and management of patients with Marfan’s syndrome are also discussed. PMID:27489631

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

    PubMed Central

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

    2016-01-01

    Background 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. Method 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) Results 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 (p<0.005, threshold 15 voxels). Interestingly the ventral striatum activation significantly correlated with the days since the last use of meth (r=−0.76, p=0.017). No significant activity was found in healthy control group. Conclusion The preliminary data suggest that methamphetamine dependent subjects, when exposed to methamphetamine-associated visual cues, have increased brain activity in ventral striatum, caudate nucleus and medial frontal cortex which subserve craving, drug-seeking, and drug use. PMID:27314105

  16. Pavlovian Discriminative Stimulus Effects of Methamphetamine in Male Japanese quail (Coturnix japonica)

    PubMed Central

    Bolin, B. Levi; Singleton, Destiny L.; Akins, Chana K.

    2014-01-01

    Pavlovian drug discrimination (DD) procedures demonstrate that interoceptive drug stimuli may come to control behavior by informing the status of conditional relationships between stimuli and outcomes. This technique may provide insight into processes that contribute to drug-seeking, relapse, and other maladaptive behaviors associated with drug abuse. The purpose of the current research was to establish a model of Pavlovian DD in male Japanese quail. A Pavlovian conditioning procedure was used such that 3.0 mg/kg methamphetamine served as a feature positive stimulus for brief periods of visual access to a female quail and approach behavior was measured. After acquisition training, generalization tests were conducted with cocaine, nicotine, and haloperidol under extinction conditions. SCH 23390 was used to investigate the involvement of the dopamine D1 receptor subtype in the methamphetamine discriminative stimulus. Results showed that cocaine fully substituted for methamphetamine but nicotine only partially substituted for methamphetamine in quail. Haloperidol dose-dependently decreased approach behavior. Pretreatment with SCH 23390 modestly attenuated the methamphetamine discrimination suggesting that the D1 receptor subtype may be involved in the discriminative stimulus effects of methamphetamine. The findings are discussed in relation to drug abuse and associated negative health consequences. PMID:24965811

  17. Correlates of Risky Alcohol and Methamphetamine Use among Currently Homeless Male Parolees

    PubMed Central

    Salem, Benissa E.; Nyamathi, Adeline; Keenan, Colleen; Zhang, Sheldon; Marlow, Elizabeth; Khalilifard, Farinaz; Yadav, Kartik; Faucette, Mark; Leake, Barbara; Marfisee, Mary

    2013-01-01

    Homeless men on parole are a hard-to-reach population with significant community reintegration challenges. This cross-sectional study describes socio-demographic, cognitive, psychosocial and drug-related correlates of alcohol and methamphetamine use in 157 homeless male parolees (age range 18–60) enrolled in a substance abuse treatment center in Los Angeles. Logistic regression results revealed that being African American and older were negatively related to methamphetamine use, while being older and more hostile were related to riskier alcohol abuse. Findings from this study provide a greater understanding of correlates of methamphetamine and alcohol- two of the most detrimental forms of substances abused among currently homeless parolees. PMID:24325770

  18. Correlates of risky alcohol and methamphetamine use among currently homeless male parolees.

    PubMed

    Salem, Benissa E; Nyamathi, Adeline; Keenan, Colleen; Zhang, Sheldon; Marlow, Elizabeth; Khalilifard, Farinaz; Yadav, Kartik; Faucette, Mark; Leake, Barbara; Marfisee, Mary

    2013-01-01

    Homeless men on parole are a hard-to-reach population with significant community reintegration challenges. This cross-sectional study describes sociodemographic, cognitive, psychosocial, and drug-related correlates of alcohol and methamphetamine use in 157 homeless male parolees (age range 18-60) enrolled in a substance abuse treatment center in Los Angeles, California. Logistic regression results revealed that being African American and older were negatively related to methamphetamine use, whereas being older and more hostile were related to riskier alcohol abuse. Findings from this study provide a greater understanding of correlates of methamphetamine and alcohol--two of the most detrimental forms of substances abused among currently homeless parolees. PMID:24325770

  19. Differential modulation of the discriminative stimulus effects of methamphetamine and cocaine by alprazolam and oxazepam in male and female rats.

    PubMed

    Spence, A L; Guerin, G F; Goeders, N E

    2016-03-01

    Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine. However, very little research has been conducted on this type of polydrug use, particularly in female subjects. The present study was therefore designed to examine the effects of two benzodiazepines, alprazolam and oxazepam, on the discriminative stimulus effects of methamphetamine and cocaine in both male and female rats. Rats were trained to discriminate methamphetamine (1.0 mg/kg, ip) or cocaine (10 mg/kg, ip) from saline using a two-lever operant, food-reinforced, drug discrimination design. Pretreatment with oxazepam (5, 10 and 20 mg/kg, ip) significantly attenuated methamphetamine discrimination in both male and female rats. In contrast, however, the high dose of alprazolam (4 mg/kg, ip) actually augmented the subjective effects of lower doses of methamphetamine (0.125 and 0.25 mg/kg, ip). Oxazepam produced similar effects on the subjective effects of cocaine as with methamphetamine, significantly reducing cocaine discrimination in both male and female rats. However, neither the high nor low dose of alprazolam (2 and 4 mg/kg, ip) produced any apparent effect on cocaine discrimination. Finally, while similar results were observed in both male and female rats across these experiments, methamphetamine and cocaine discrimination were more sensitive to oxazepam in female subjects. The results of these experiments suggest that alprazolam and oxazepam can differentially affect the subjective effects of methamphetamine and cocaine. These results also demonstrate that alprazolam can differentially affect the discriminative stimulus effects of methamphetamine and cocaine. PMID:26541330

  20. Male methamphetamine-user inmates in prison treatment: during-treatment outcomes.

    PubMed

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

    2010-03-01

    Psychosocial functioning and criminal thinking of methamphetamine-using inmates were examined before and after their completion of primary treatment in three in-prison drug treatment programs (one "outpatient" and two different modified therapeutic communities [TCs]). The sample consisted of 2,026 adult male inmates in 30 programs in Indiana. Data included background, psychosocial functioning, criminal thinking, and therapeutic engagement indicators. Multilevel repeated measures analysis was used to evaluate changes during treatment, and multilevel covariate analysis adjusted for sample differences in tests of between-treatment differences. Significant improvements were found for all three treatments, but the two modified TCs showed significantly better progress than did outpatient treatment housed among the general prison population. Significant predictors of treatment progress included baseline psychosocial functioning and background, wherein higher psychosocial functioning and lower criminal thinking orientation predicted stronger therapeutic engagement. However, treatment engagement level was found to mediate during-treatment improvement and initial criminal thinking. PMID:19801177

  1. Hippocampal volume reduction in female but not male recent abstinent methamphetamine users.

    PubMed

    Du, Jiang; Quan, Meina; Zhuang, Wenxu; Zhong, Na; Jiang, Haifeng; Kennedy, David N; Harrington, Amy; Ziedonis, Douglas; Fan, Xiaoduo; Zhao, Min

    2015-08-01

    Growing evidence suggests abnormalities in brain morphology including hippocampal structure in patients with methamphetamine (MA) dependence. This study was performed to examine hippocampal volume in abstinent MA users, and to further explore its relationship with cognitive function. 30 abstinent MA users (20 males and 10 females) with average 5.52 months of duration of abstinence and 29 healthy controls (19 males and 10 females) age 18-45 years old were recruited for clinical assessment and imaging scan. FreeSurfer was used to segment the hippocampus bilaterally, and hippocampal volumes were extracted for group and gender comparisons. Cognitive function was measured using the CogState Battery Chinese language version (CSB-C). Analysis of covariance (ANCOVA) controlling for education showed a significant group by gender interaction for the right hippocampal relative volume adjusted for total brain size (p = 0.020); there was a significant difference between male controls and female controls (p < 0.001), but such a difference did not exist between male patients and female patients (p = 0.203). No significant correlations were found between hippocampal volume and cognitive measures. There seems to be a gender difference in how MA affects hippocampal volume in abstinent MA users. Hippocampus might be an important treatment target for cognitive improvement and functional recovery in this patient population, especially in females. PMID:25920682

  2. Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

    PubMed

    Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

    2011-10-10

    Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test. PMID:21645557

  3. Correlates of Heroin and Methamphetamine Use among Homeless Male Ex-Jail and Prison Offenders

    PubMed Central

    Nyamathi, Adeline; Salem, Benissa E.; Farabee, David; Hall, Elizabeth; Zhang, Sheldon; Marfisee, Mary; Khalilifard, Farinaz; Musto, Stefanie; Leake, Barbara

    2014-01-01

    Homeless men exiting California State jails and prisons are a heterogeneous community with varied childhood, incarceration and drug use histories. This cross-sectional study assessed whether homeless men who were discharged from either jail or prison into a residential substance abuse treatment program, differed in terms of methamphetamine and heroin use. This study utilized baseline data collected on 540 recently paroled men randomized to one of three programs that assessed the impact of a peer coaching intervention on subsequent drug use and re-incarceration. We found that younger ex-offenders exiting prisons and jails were more likely to have used methamphetamine alone, whereas African American ex-offenders were less likely to have used methamphetamine alone when compared to other ethnic groups. Further, ex-offenders exiting jails and self-reporting use of heroin only at baseline were significantly more likely than their counterparts to have been removed from home before age 18. For men exiting jails, there was an association between lower self-esteem and having used methamphetamine but not heroin. However, having used both heroin and methamphetamine was associated with both violent crime and cognitive problems in both jail and prison samples. Our findings showcase the need to understand unique correlates of both heroin and methamphetamine as they relate to jail and prison populations. PMID:25489295

  4. Does prenatal methamphetamine exposure induce cross-sensitization to cocaine and morphine in adult male rats?

    PubMed

    Slamberová, R; Yamamotová, A; Pometlová, M; Schutová, B; Hrubá, L; Nohejlová-Deykun, K; Nová, E; Macúchová, E

    2012-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected. PMID:22980560

  5. Methamphetamine overdose

    MedlinePlus

    ... methamphetamine overdose may be acute (sudden) or chronic (long-term). An acute methamphetamine overdose occurs when someone takes ... kidney failure Paranoia Seizures Severe stomach pain Stroke Long-term use of methamphetamine can lead to significant psychological ...

  6. Androgen-primed castrate males are sufficient for methamphetamine-facilitated increases in proceptive behavior in female rats.

    PubMed

    Rudzinskas, Sarah A; Mong, Jessica A

    2016-02-01

    Methamphetamine (MA) is a psychomotor stimulant associated with increases in sex drive in both men and women. Women, however, are far more likely to face social disadvantages as a consequence of MA use, and their increased sexual motivation poses additional health concerns such as unplanned pregnancies. To better understand the mechanisms underlying MA-facilitated sexual motivation in females, we previously established a rodent model where a "binge"-type administration paradigm of MA to sexually receptive female rats significantly increases proceptive behavior in the presence of a sexually active, gonadally-intact male. Our previous work with this model has led us to consider whether the increases in proceptive behavior are truly indicative of increased sexual motivation, or instead a consequence of heightened motor responsivity. Here, we test whether MA-induced increases in proceptive behaviors are specific to a sexually relevant stimulus. Females' sexual, social, exploratory behaviors, and interaction times were scored during the exposure to stimulus males, including castrates, and dihydrotestosterone (DHT)-treated castrates. MA-treated females demonstrated significant increases in proceptive behaviors toward DHT-treated castrate males but not toward castrate males. While the non-MA-treated females did display proceptive behavior, there was no significant difference between behaviors elicited by DHT-CX males compared to CX males. Our results support the hypothesis that MA facilitates proceptive behavior only in response to specific, androgen mediated sexually-relevant cues. PMID:26497407

  7. Orexin-A level elevation in recently abstinent male methamphetamine abusers.

    PubMed

    Chen, Wen-Yin; Kao, Chung-Feng; Chen, Po-Yu; Lin, Shih-Ku; Huang, Ming-Chyi

    2016-05-30

    Research has suggested that methamphetamine (METH) use influences orexin regulation. We examined the difference in orexin-A levels between METH abusers and healthy controls. Fasting serum orexin-A levels were measured in 35 participants who used METH in the preceding 3 weeks and 36 healthy controls. We found METH abusers had significantly higher orexin-A levels. No association was observed between orexin-A levels and METH use variables. Our results, consistent with prior preclinical evidence, showed that recent METH exposure is associated with increased orexin-A expression. Further investigation is required to determine whether orexin-A levels normalize after a longer term of abstinence. PMID:27137956

  8. Predictors of relapse in Filipino male methamphetamine users: a mixed methods approach.

    PubMed

    Tuliao, Antover P; Liwag, Maria Emma Concepcion D

    2011-01-01

    Using a simultaneous mixed methods design, this article studies the relapse predictors of Filipino methamphetamine abusers. Results of the quantitative study, with 32 relapsed and 19 abstaining individuals, indicate that self-efficacy, negative affect, motivation, coping, and craving were found to predict relapse and functional social support did not. In-depth interviews with 11 relapse and 10 abstaining individuals supported the quantitative study. Although the results mirror existing literature, the issue of social support was given emphasis in the discussion. Implications for treatment, limitations, and recommendations for future study are also discussed. PMID:21678148

  9. Methamphetamine: Glossary

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... e.g., methylphenidate and amphetamines), as well as cocaine and methamphetamine. Tolerance: A condition in which higher ...

  10. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.

    PubMed

    Banks, Matthew L; Smith, Douglas A; Blough, Bruce E

    2016-04-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID:26886209

  11. Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

    PubMed

    Šlamberová, R; Pometlová, M; Schutová, B; Hrubá, L; Macúchová, E; Nová, E; Rokyta, R

    2012-01-01

    Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test. PMID:23130898

  12. Persistent Microstructural Deficits of Internal Capsule in One-Year Abstinent Male Methamphetamine Users: a Longitudinal Diffusion Tensor Imaging Study.

    PubMed

    Zhuang, Wenxu; Tang, Yingying; Zhong, Na; Jiang, Haifeng; Du, Jiang; Wang, Jijun; Zhao, Min

    2016-09-01

    White matter (WM) alterations have been reported in methamphetamine (MA) users. However, knowledge about longitudinal changes in WM during abstinence from MA remains unknown. The present study aimed to examine how WM changes in long-term MA abstinent, in particular, whether the WM deficits would recover as the duration of abstinence extended. Twenty male MA dependent individuals and 19 healthy controls (HCs) were recruited and participated in both clinical assessments and diffusion tensor imaging (DTI) scans. The MA group underwent two DTI scans, a baseline scan with a duration of abstinence of 6.4 months and and a follow-up scan with a duration of abstinence of 13.0 months. Tract-Based Spatial Statistics was utilized to conduct baseline DTI analysis of MA group compared with HCs. The clusters with significant group differences of factional anisotropy (FA) were extracted as region of interests (ROIs). Mean values of DTI measurements (FA, mean diffusivity, axial diffusivity and radial diffusivity) were calculated within the ROIs in each subject's native space at baseline and follow-up. The MA group showed significant lower FA in the right internal capsule and superior corona radiate than HCs. The deficits did not recover when the duration of abstinence from MA reached 13 months. No significant correlations were found between FA and clinical measurements. Our results suggested persistent microstructure deficits of WM tracts surrounding the basal ganglia in MA dependent individuals. PMID:27115910

  13. How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Ševčíková, M; Hrebíčková, I; Nohejlová, K; Šlamberová, R

    2016-06-01

    Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the

  14. Methamphetamine overdose

    MedlinePlus

    ... regular basis. Injuries during illegal methamphetamine production or police raids include exposure to dangerous chemicals, as well ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  15. Methamphetamine (Meth)

    MedlinePlus

    ... effects, similar to those of other stimulants like cocaine. These include: Feeling very awake and active Fast ... Methamphetamine is a stimulant, with effects similar to cocaine, but longer-lasting. It does not cause illness ...

  16. Mind Over Matter: Methamphetamine

    MedlinePlus

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Methamphetamine Print Mind Over Matter: Methamphetamine (Meth) Order Free Publication in: English Spanish Download PDF 739.54 KB Methamphetamine comes in ...

  17. Chronic methamphetamine exposure prior to middle cerebral artery occlusion increases infarct volume and worsens cognitive injury in Male mice.

    PubMed

    Zuloaga, Damian G; Wang, Jianming; Weber, Sydney; Mark, Gregory P; Murphy, Stephanie J; Raber, Jacob

    2016-08-01

    Emerging evidence indicates that methamphetamine (MA) abuse can impact cardiovascular disease. In humans, MA abuse is associated with an increased risk of stroke as well as an earlier age at which the stroke occurs. However, little is known about how chronic daily MA exposure can impact ischemic outcome in either humans or animal models. In the present study, mice were injected with MA (10 mg/kg, i.p.) or saline once daily for 10 consecutive days. Twenty-four hours after the final injection, mice were subjected to transient middle cerebral artery occlusion (tMCAO) for one hour followed by reperfusion. Mice were tested for novel object memory at 96 h post-reperfusion, just prior to removal of brains for quantification of infarct volume using 2,3,5-Triphenyltetrazolium Chloride (TTC) staining. Mice treated with MA prior to tMCAO showed decreased object memory recognition and increased infarct volume compared to saline-treated mice. These findings indicate that chronic MA exposure can worsen both cognitive and morphological outcomes following cerebral ischemia. PMID:27021292

  18. Research Reports: Methamphetamine

    MedlinePlus

    ... Publications » Research Reports » Methamphetamine » Letter from the Director Methamphetamine Email Facebook Twitter Letter from the Director The abuse of methamphetamine—a potent and highly addictive stimulant—remains an ...

  19. Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

    PubMed Central

    Hart, Carl L; Gunderson, Erik W; Perez, Audrey; Kirkpatrick, Matthew G; Thurmond, Andrew; Comer, Sandra D; Foltin, Richard W

    2016-01-01

    Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID:17851535

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

    PubMed

    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 < 0.001) in males but not females. We then examined rs7591784 and 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

  1. Crystal methamphetamine initiation among street-involved youth

    PubMed Central

    Uhlmann, Sasha; DeBeck, Kora; Simo, Annick; Kerr, Thomas; Montaner, Julio S. G.; Wood, Evan

    2014-01-01

    Background Although many settings have recently documented a substantial increase in the use of methamphetamine-type stimulants, recent reviews have underscored the dearth of prospective studies that have examined risk factors associated with the initiation of crystal methamphetamine use. Objectives Our objectives were to examine rates and risk factors for the initiation of crystal methamphetamine use in a cohort of street-involved youth. Methods Street-involved youth in Vancouver, Canada, were enrolled in a prospective cohort known as the At-Risk Youth Study (ARYS). A total of 205 crystal methamphetamine-naïve participants were assessed semi-annually and Cox regression analyses were used to identify factors independently associated with the initiation of crystal methamphetamine use. Results Among 205 youth prospectively followed from 2005 to 2012, the incidence density of crystal methamphetamine initiation was 12.2 per 100 person years. In Cox regression analyses, initiation of crystal methamphetamine use was independently associated with previous crack cocaine use (adjusted relative hazard [ARH] = 2.24 [95% CI: 1.20–4.20]) and recent drug dealing (ARH = 1.98 [95% CI: 1.05–3.71]). Those initiating methamphetamine were also more likely to report a recent nonfatal overdose (ARH = 3.63 [95% CI: 1.65–7.98]) and to be male (ARH = 2.12 [95% CI: 1.06–4.25]). Conclusions We identified high rates of crystal methamphetamine initiation among this population. Males those involved in the drug trade, and those who used crack cocaine were more likely to initiate crystal methamphetamine use. Evidence-based strategies to prevent and treat crystal methamphetamine use are urgently needed. PMID:24191637

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

    PubMed

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

    2014-07-01

    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

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

    PubMed Central

    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

  4. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits

    PubMed Central

    Vieira-Brock, Paula L.; McFadden, Lisa M.; Nielsen, Shannon M.; Smith, Misty D.; Hanson, Glen R.

    2015-01-01

    Background: Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Methods: Adolescent or adult male Sprague-Dawley rats received either nicotine water (10–75 μg/mL) or tap water for several weeks. Methamphetamine (4×7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Results: Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Conclusions: Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which

  5. The methamphetamine problem

    PubMed Central

    Galbraith, Niall

    2015-01-01

    This paper introduces the reader to the characteristics of methamphetamine. Explored within are the drug's effects on those who consume it as well as the history and prevalence of its use. The highly addictive nature of methamphetamine is compounded by its affordability and the ease with which it is produced, with North America and East Asia having become established as heartlands for both consumption and manufacture. The paper discusses recent cultural depictions of the drug and also the role that mental health professionals may take in designing and delivering interventions to treat methamphetamine addiction. PMID:26755964

  6. Methamphetamine Use in Club Subcultures

    PubMed Central

    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

  7. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

  8. The Cardiac Complications of Methamphetamines.

    PubMed

    Paratz, Elizabeth D; Cunningham, Neil J; MacIsaac, Andrew I

    2016-04-01

    Methamphetamines are increasingly popular drugs of abuse in Australia, and are rising in purity. The rising popularity and purity of methamphetamines has notably increased demands upon Australian medical services. Methamphetamines are sympathomimetic amines with a range of adverse effects upon multiple organ systems. Cardiovascular complications are the second leading cause of death in methamphetamine abusers, and there appears to be a high prevalence of cardiac pathology. Cardiovascular pathology frequently seen in methamphetamine abusers includes hypertension, aortic dissection, acute coronary syndromes, pulmonary arterial hypertension and methamphetamine-associated cardiomyopathy. The rising prevalence of methamphetamine abuse is likely to increase the burden of cardiovascular pathology in Australians. A National Parliamentary Enquiry was opened in March 2015 to address concerns regarding the medical and social impacts of methamphetamine abuse. From April 2015, a National 'Ice Taskforce' was also created in parallel. Reversal of cardiac pathology appears to be achievable with abstinence from methamphetamines and initiation of appropriate treatment. It is key to appreciate that the pathogenesis of methamphetamine-induced cardiac complications arises as a result of the specific toxic effects of methamphetamines. Clinical management is hence individualised; suggested management approaches for methamphetamine-induced cardiac complications are detailed within this article. PMID:26706652

  9. Initiation into Methamphetamine Use For Young Gay and Bisexual Men

    PubMed Central

    Parsons, Jeffrey T.; Kelly, Brian C.; Weiser, Jonathan D.

    2007-01-01

    Research over the past ten years has suggested that methamphetamine use has become a significant problem and is associated with risky sexual behaviors among gay and bisexual men. In order to better understand initiation into methamphetamine use among gay and bisexual men, qualitative analyses were performed on a sample of young gay and bisexual men (ages 18-29) in New York City. Participants were recruited as part of a larger study which used time-space sampling to enroll club-going young adults who indicated recent club-drug (ecstasy, ketamine, GHB, methamphetamine, cocaine, and/or LSD) use. The data for this paper are derived from the qualitative interviews of 54 gay and bisexual male methamphetamine users. At initiation (1) Methamphetamine was used in a social, non-sexual setting for a majority of the participants; (2) participants expressed limited knowledge of methamphetamine; and (3) many participants used cocaine as a basis for comparison when describing various effects of the drug. The understanding that at initiation methamphetamine was not solely used as a sexual enhancement for members of this community may enable health workers to more accurately target potential users when putting forth intervention efforts. Future research should aim to gain a better understanding into the role that methamphetamine plays in non-sexual contexts, particularly among gay and bisexual men who may not be part of the club “scene.” The relationship between attitudes towards methamphetamine and other drugs, particularly cocaine, among gay and bisexual men should be explored. PMID:17398040

  10. Methamphetamine and Parkinson's Disease

    PubMed Central

    Granado, Noelia; Ares-Santos, Sara; Moratalla, Rosario

    2013-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. PMID:23476887

  11. Gender Differences in the Effect of Tobacco Use on Brain Phosphocreatine Levels in Methamphetamine Dependent Subjects

    PubMed Central

    Sung, Young-Hoon; Yurgelun-Todd, Deborah A.; Kondo, Douglas G.; Shi, Xian-Feng; Lundberg, Kelly J.; Hellem, Tracy L.; Huber, Rebekah S.; McGlade, Erin C.; Jeong, Eun-Kee; Renshaw, Perry F.

    2015-01-01

    Background A high prevalence of tobacco smoking has been observed in methamphetamine users, but there have been no in vivo brain neurochemistry studies addressing gender effects of tobacco smoking in methamphetamine users. Methamphetamine addiction is associated with increased risk of depression and anxiety in females. There is increasing evidence that selective analogues of nicotine, a principal active component of tobacco smoking, may improve depression and cognitive performance in animals and humans. Objectives To investigate the effects of tobacco smoking and gender on brain phosphocreatine (PCr) levels, a marker of brain energy metabolism reported to be reduced in methamphetamine-dependent subjects. Methods Thirty female and twenty-seven male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. Results Analysis of covariance revealed that there were statistically significant slope (PCr versus lifetime amount of tobacco smoking) differences between female and male methamphetamine-dependent subjects (p=0.03). In females, there was also a statistically significant interaction between lifetime amounts of tobacco smoking and methamphetamine in regard to PCr levels (p=0.01), which suggests that tobacco smoking may have a more significant positive impact on brain PCr levels in heavy, as opposed to light to moderate, methamphetamine-dependent females. Conclusion These results indicate that tobacco smoking has gender-specific effects in terms of increased anterior cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette smoking in methamphetamine-dependent women, particularly those with heavy methamphetamine use, may have a potentially protective effect upon neuronal metabolism. PMID:25871447

  12. Long-term effects of methamphetamine exposure on cognitive function and muscarinic acetylcholine receptor levels in mice

    PubMed Central

    Siegel, Jessica A.; Craytor, Michael J.; Raber, Jacob

    2010-01-01

    Exposure to methamphetamine during brain development impairs cognition in humans and rodents. In mice, these impairments are greater in females than males. Genetic factors, such as apolipoprotein E genotype, may modulate the cognitive effects of methamphetamine. Methamphetamine-induced alterations in the brain acetylcholine system may contribute to the cognitive effects of methamphetamine and may also be modulated by apolipoprotein E isoform. We assessed the long-term effects of methamphetamine exposure during brain development on cognitive function and muscarinic acetylcholine receptors in mice, and whether apolipoprotein E isoform modulates these effects. Mice expressing human apolipoprotein E3 or E4 were exposed to methamphetamine (5 mg/kg) or saline once a day from postnatal day 11-20 and behaviorally tested in adulthood. Muscarinic acetylcholine receptor binding was measured in the hippocampus and cortex. Methamphetamine exposure impaired novel location recognition in female, but not male, mice. Methamphetamine-exposed male and female mice showed impaired novel object recognition and increased number of muscarinic acetylcholine receptors in the hippocampus. The cognitive and cholinergic effects of methamphetamine were similar in apolipoprotein E3 and E4 mice. Thus, the cholinergic system, but not apolipoprotein E isoform, might play an important role in the long-term methamphetamine-induced cognitive deficits in adulthood. PMID:20729719

  13. Enhanced Upregulation of CRH mRNA Expression in the Nucleus Accumbens of Male Rats after a Second Injection of Methamphetamine Given Thirty Days Later

    PubMed Central

    Cadet, Jean Lud; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T.; Krasnova, Irina N.; Lehrmann, Elin; Becker, Kevin G.; Jayanthi, Subramaniam

    2014-01-01

    Methamphetamine (METH) is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg) on transcriptional effects of a second METH (2.5 mg/kg) injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc) of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS) or METH-challenged (SM); and METH-pretreated followed by saline-challenged (MS) or METH-challenged (MM). Microarray analyses revealed that METH (2.5 mg/kg) produced acute changes (1.8-fold; P<0.01) in the expression of 412 (352 upregulated, 60 down-regulated) transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh), oxytocin (Oxt), and vasopressin (Avp) that were upregulated. Injection of METH (10 mg/kg) altered the expression of 503 (338 upregulated, 165 down-regulated) transcripts measured one month later (MS group). These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated) transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug. PMID:24475032

  14. Acute Iodine Toxicity From a Suspected Oral Methamphetamine Ingestion

    PubMed Central

    Bulloch, Marilyn N

    2014-01-01

    BACKGROUND Iodine is a naturally occurring element commercially available alone or in a multitude of products. Iodine crystals and iodine tincture are used in the production of methamphetamine. Although rarely fatal, iodine toxicity from oral ingestion can produce distressing gastrointestinal symptoms and systemic symptoms, such as hypotension and tachycardia, from subsequent hypovolemia. OBJECTIVE The objective of this case report is to describe a case of iodine toxicity from suspected oral methamphetamine ingestion. CASE REPORT A male in his early 20’s presented with gastrointestinal symptoms, chills, fever, tachycardia, and tachypnea after orally ingesting a substance suspected to be methamphetamine. The patient had elevated levels of serum creatinine, liver function tests, and bands on arrival, which returned to within normal limits by day 4 of admission. Based on the patient’s narrow anion gap, halogen levels were ordered on day 3 and indicated iodine toxicity. This is thought to be the first documented case of iodine toxicity secondary to suspected oral methamphetamine abuse. CONCLUSION Considering that the incidence of methamphetamine abuse is expected to continue to rise, clinicians should be aware of potential iodine toxicity in a patient with a history of methamphetamine abuse. PMID:25452705

  15. A review of treatment options for co-occurring methamphetamine use disorders and depression.

    PubMed

    Hellem, Tracy L; Lundberg, Kelly J; Renshaw, Perry F

    2015-01-01

    Co-occurring methamphetamine use and depression interferes with treatment outcomes. Female methamphetamine users are known to have higher rates of depression than male methamphetamine users, although this is also true for the general population. There are limited treatment options for the management of depression among methamphetamine users. In this integrative review, we summarize data on treatment strategies for co-occurring depression and methamphetamine use disorders. English-language articles were identified from PsychINFO, CINAHL, PubMed, and Medline as well as from reference lists of key articles. Search terms included "methamphetamine," "depression," and "treatment." Research articles describing psychological (n = 3), pharmacological (n = 6), nutritional supplement (n = 1), and psychological combined with pharmacological (n = 3) approaches for the treatment of methamphetamine use or withdrawal and/or depression are included in this review. Psychological and combination of psychological with pharmacological approaches have not been shown to be effective in treating these co-occurring conditions. Antidepressants have been determined to be ineffective and/or to introduce side effects. Gender differences with response to treatment were examined in only one of the published studies. There is a large gap in knowledge regarding treatment of co-occurring methamphetamine use disorders and depression. Considering that female methamphetamine users experience higher rates of depression than men, a focus on gender-specific treatment approaches is warranted. PMID:25761159

  16. Perceived Risk of Methamphetamine among Chinese Methamphetamine Users

    PubMed Central

    Kelly, Brian C; Liu, Tieqiao; Yang, Xiaozhao Yosef; Zhang, Guanbai; Hao, Wei; Wang, Jichuan

    2014-01-01

    Background Methamphetamine use has grown considerably in China in recent years. Information about perceptions of risk on methamphetamine is important to facilitate health promotion efforts. Methods Using both survey data and qualitative interview data, the authors evaluate the perceived risk of methamphetamine use among Chinese users using a mixed-methods approach. Through Respondent Driven Sampling, the authors recruited a sample of 303 methamphetamine users in Changsha, China. Results A majority (59.1%) perceive that infrequent methamphetamine use poses no risk to the user, while 11.2% perceive at least moderate risk for light use. A majority (56.7%) perceived at least moderate risk associated with regular methamphetamine use. Most (82.2%) also perceive methamphetamine to be easily obtainable. A path model indicates that perceived risk shapes intentions to use and expectations of future use, as does perceived availability. Qualitatively, while addiction was the most common risk discussed by users, they differed on whether they perceived the drug addictive. Other concerns raised by interviewees included impaired cognition, mental health problems, physical harm, and social dysfunction. Discussion While some users identify significant risks with methamphetamine, others do not perceive its use to be problematic. Collectively, these findings indicate that intervening upon perceptions of risk among Chinese methamphetamine users may be a means to influence intentions to use. PMID:24925820

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

    PubMed

    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. PMID:21858954

  18. EFFECTS OF TOPIRAMATE ON METHAMPHETAMINE-INDUCED CHANGES IN ATTENTIONAL AND PERCEPTUAL-MOTOR SKILLS OF COGNITION IN RECENTLY ABSTINENT METHAMPHETAMINE-DEPENDENT INDIVIDUALS

    PubMed Central

    Johnson, Bankole A.; Roache, John D.; Ait-Daoud, Nassima; Wells, Lynda T.; Wallace, Christopher L.; Dawes, Michael A.; Liu, Lei; Wang, Xin-Qun

    2007-01-01

    Methamphetamine-dependent individuals often cite the need to maintain enhanced cognitive performance and attention as a reason for continuing or relapsing to drug-taking. Further, methamphetamine addicts might not comply with taking a potentially therapeutic medication if it had a profound effect on these cognitive processes. Topiramate, a sulfamate-substituted fructopyranose derivative, has been suggested as a putative therapeutic medication for treating methamphetamine dependence. Examination of topiramate’s effects on cognitive performance and attention is a clinically and scientifically important component of understanding its potential therapeutic profile. In 10 male and female individuals who met DSM-IV criteria for methamphetamine dependence, we examined the effects of low (50 mg b.i.d.)- and high (100 mg b.i.d.)-dose topiramate — in both the presence and absence of low (15 mg)- and high (30 mg)-dose intravenous methamphetamine — on cognitive performance, attention, and concentration on the rapid visual information processing task and the digit symbol substitution test. Intravenous methamphetamine enhanced cognitive performance, attention, and concentration among recently withdrawn methamphetamine addicts — an effect that hitherto had not been well characterized. Topiramate’s cognitive effects were mixed and rather paradoxical, with a tendency to improve attention and concentration both alone and in the presence of methamphetamine while worsening psychomotor retardation. No deleterious interaction occurred between topiramate and methamphetamine on any of these cognitive processes. While clinical studies with topiramate should prepare participants for possible psychomotor retardation, the cognitive-effects profile observed would not likely present an important obstacle to compliance in motivated patients. Topiramate’s complicated cognitive effects among methamphetamine addicts need more comprehensive examination. PMID:16978753

  19. The effect of early environmental manipulation on locomotor sensitivity and methamphetamine conditioned place preference reward.

    PubMed

    Hensleigh, E; Pritchard, L M

    2014-07-15

    Early life stress leads to several effects on neurological development, affecting health and well-being later in life. Instances of child abuse and neglect are associated with higher rates of depression, risk taking behavior, and an increased risk of drug abuse later in life. This study used repeated neonatal separation of rat pups as a model of early life stress. Rat pups were either handled and weighed as controls or separated for 180 min per day during postnatal days 2-8. In adulthood, male and female rats were tested for methamphetamine conditioned place preference reward and methamphetamine induced locomotor activity. Tissue samples were collected and mRNA was quantified for the norepinephrine transporter in the prefrontal cortex and the dopamine transporter in the nucleus accumbens. Results indicated rats given methamphetamine formed a conditioned place preference, but there was no effect of early separation or sex. Separated males showed heightened methamphetamine-induced locomotor activity, but there was no effect of early separation for females. Overall females were more active than males in response to both saline and methamphetamine. No differences in mRNA levels were observed across any conditions. These results suggest early neonatal separation affects methamphetamine-induced locomotor activity in a sex-dependent manner but has no effects on methamphetamine conditioned place preference. PMID:24713150

  20. THE EFFECT OF EARLY ENVIRONMENTAL MANIPULATION ON LOCOMOTOR SENSITIVITY AND METHAMPHETAMINE CONDITIONED PLACE PREFERENCE REWARD

    PubMed Central

    Hensleigh, E.; Pritchard, L. M.

    2014-01-01

    Early life stress leads to several effects on neurological development, affecting health and well-being later in life. Instances of child abuse and neglect are associated with higher rates of depression, risk taking behavior, and an increased risk of drug abuse later in life. This study used repeated neonatal separation of rat pups as a model of early life stress. Rat pups were either handled and weighed as controls or separated for 180 minutes per day during postnatal days 2-8. In adulthood, male and female rats were tested for methamphetamine conditioned place preference reward and methamphetamine induced locomotor activity. Tissue samples were collected and mRNA was quantified for the norepinephrine transporter in the prefrontal cortex and the dopamine transporter in the nucleus accumbens. Results indicated rats given methamphetamine formed a conditioned place preference, but there was no effect of early separation or sex. Separated males showed heightened methamphetamine-induced locomotor activity, but there was no effect of early separation for females. Overall females were more active than males in response to both saline and methamphetamine. No differences in mRNA levels were observed across any conditions. These results suggest early neonatal separation affects methamphetamine-induced locomotor activity in a sex-dependent manner but has no effects on methamphetamine conditioned place preference. PMID:24713150

  1. The effects of adolescent methamphetamine exposure

    PubMed Central

    Buck, Jordan M.; Siegel, Jessica A.

    2015-01-01

    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. PMID:25972781

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

    PubMed

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

    2015-04-01

    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 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. PMID:25678251

  3. Chlorogenic and Caftaric Acids in Liver Toxicity and Oxidative Stress Induced by Methamphetamine

    PubMed Central

    Koriem, Khaled M. M.; Soliman, Rowan E.

    2014-01-01

    Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective. PMID:25136360

  4. Methamphetamine Use by High School Students: Recent Trends, Gender and Ethnicity Differences, and Use of Other Drugs.

    ERIC Educational Resources Information Center

    Oetting, Eugene R.; Deffenbacher, Jerry L.; Taylor, Matthew J.; Luther, Nathan; Beauvais, Fred; Edwards, Ruth W.

    2000-01-01

    Recent data on 9th-12th grade methamphetamine use (both lifetime and last month prevalence) are summarized. Since 1992 methamphetamine use has increased. There were no significant differences in use noted across school year. Males are more likely to use than females, although female use has also increased. Implications for research, prevention,…

  5. Methamphetamine Cured my Cocaine Addiction.

    PubMed

    Haile, Colin N; De La Garza, Richard; Newton, Thomas F

    2010-10-14

    Cocaine dependence is an enduring problem and years of research and drug development has yet to produce an efficacious pharmacotherapy. Recent clinical research suggests that chronic treatment with amphetamine-like medications produces tolerance to cocaine's reinforcing effects and may offer a viable pharmacotherapy. Three methamphetamine-dependent participants that had been in our clinical laboratory experiments and previously addicted to cocaine are reviewed. Data obtained from initial screen and informal conversation suggested that all participants considered methamphetamine to have helped them stop using cocaine and eliminate cocaine craving. Methamphetamine also significantly decreased their alcohol consumption but did not alter cannabis or nicotine use. PMID:23066512

  6. Methamphetamine Cured my Cocaine Addiction

    PubMed Central

    Haile, Colin N.; De La Garza, Richard; Newton, Thomas F.

    2011-01-01

    Cocaine dependence is an enduring problem and years of research and drug development has yet to produce an efficacious pharmacotherapy. Recent clinical research suggests that chronic treatment with amphetamine-like medications produces tolerance to cocaine’s reinforcing effects and may offer a viable pharmacotherapy. Three methamphetamine-dependent participants that had been in our clinical laboratory experiments and previously addicted to cocaine are reviewed. Data obtained from initial screen and informal conversation suggested that all participants considered methamphetamine to have helped them stop using cocaine and eliminate cocaine craving. Methamphetamine also significantly decreased their alcohol consumption but did not alter cannabis or nicotine use. PMID:23066512

  7. Remission of Methamphetamine-Induced Withdrawal Delirium and Craving After Electroconvulsive Therapy

    PubMed Central

    Ahmadi, Jamshid; Ekramzadeh, Sara; Pridmore, Saxby

    2015-01-01

    Introduction: The aim of this study is to describe the use of electroconvulsive therapy (ECT) in the treatment of methamphetamine-induced withdrawal delirium and craving in a single case. Case Presentation: A 44-year-old male presented to the hospital in Fars province, Iran, with Methamphetamine-Induced Withdrawal Delirium who responded to ECT. Conclusions: The electroconvulsive therapy can be a suitable option for the treatment of methamphetamine withdrawal delirium and craving. Also, it can be usefully employed in these very serious conditions which may represent a risk to life. PMID:26834801

  8. Impulsivity and methamphetamine use.

    PubMed

    Semple, Shirley J; Zians, Jim; Grant, Igor; Patterson, Thomas L

    2005-09-01

    The purpose of this study was to explore the relationship between methamphetamine (meth) use and impulsivity in a sample of 385 HIV-negative heterosexually identified meth users. Participants who scored highest on a self-report measure of impulsivity were compared with those who scored lower in terms of background characteristics, meth use patterns, use of alcohol and other illicit drugs, sexual risk behavior, and psychiatric health variables. Methamphetamine users in the high impulsivity group were younger, less educated, used larger quantities of meth, were more likely to be binge users, had a larger number of sexual partners, engaged in more unprotected vaginal and oral sex, and scored higher on the Beck Depression Inventory as compared with those in the low impulsivity group. In a logistic regression analysis, Beck depression was the factor that best distinguished between meth users who scored high and those who scored low on impulsivity. Neurophysiological pathways that may underlie the relationship between impulsivity and meth use are discussed. PMID:16135337

  9. At the Borders, on the Edge: Use of Injected Methamphetamine in Tijuana and Ciudad Juarez, Mexico

    PubMed Central

    Ramos, Rebeca; Brouwer, Kimberly C.; Firestone-Cruz, Michelle; Pollini, Robin A.; Strathdee, Steffanie A.; Fraga, Miguel A.; Patterson, Thomas L.

    2009-01-01

    Injection drug use is of increasing concern along the US–Mexico border where Tijuana and Ciudad (Cd.) Juarez are located. Methamphetamine has long been manufactured and trafficked through Mexico, with low rates of use within Mexico. With methamphetamine use now considered epidemic in the United States, and with associated individual and community harms such as HIV, STDs, domestic violence and crime, there is concern that rates of methamphetamine in the Northwestern border regions of Mexico may be rising. We conducted a qualitative study to explore the context of injection drug use in Tijuana and Cd. Juarez and included questions about methamphetamine. Guided in-depth interviews were conducted with 10 male and 10 female injection drug users (IDUs) in Tijuana and 15 male and 8 female IDUs in Cd. Juarez (total N = 43). Topics included types of drug used, injection settings, access to sterile needles and environmental influences. Interviews were taped, transcribed verbatim and translated. Content analysis was conducted to identify themes. The median age of injectors in both cities was 30. Methamphetamine was injected, either alone or in combination with other drugs by injectors in both Tijuana (85%) and Cd. Juarez (17%) in the 6 months previous to interview. Several important themes emerged with respect to methamphetamine use in both cities. IDUs in both cities considered methamphetamine to be widely used in Tijuana and infrequently used in Cd. Juarez, while the converse was true for cocaine. In both cities, stimulant (either cocaine or methamphetamine) use was widespread, with 85% in Tijuana and 83% in Cd. Juarez reporting current use of a stimulant, most often used in combination with heroin. Some injectors reported knowledge of local manufacturing and one had direct experience in making methamphetamine; some cross-border use and trafficking was reported. Injectors reported concerns or experience with serious health effects of methamphetamine such as abscesses or

  10. Sigma (σ) Receptor Ligand, AC927 (N-Phenethylpiperidine Oxalate), Attenuates Methamphetamine-Induced Hyperthermia and Serotonin Damage in Mice

    PubMed Central

    Seminerio, Michael J.; Kaushal, Nidhi; Shaikh, Jamaluddin; Huber, Jason D.; Coop, Andrew; Matsumoto, Rae R.

    2013-01-01

    Methamphetamine interacts with sigma (σ) receptors and AC927, a selective σ receptor ligand, protects against methamphetamine-induced dopaminergic neurotoxicity. In the present study, the effects of AC927 on methamphetamine-induced hyperthermia and striatal serotonergic neurotoxicity were evaluated. Male, Swiss Webster mice were injected (i.p.) every two hours, for a total of four times, with one of the following treatments: Saline + Saline; Saline + Methamphetamine (5 mg/kg); AC927 (5, 10, 20 mg/kg) + Methamphetamine (5 mg/kg); or AC927 (5, 10, 20 mg/kg) + Saline. Pretreatment with AC927 (10 mg/kg) significantly attenuated methamphetamine-induced striatal serotonin depletions, striatal serotonin transporter reductions, and hyperthermia. At the doses tested, AC927 itself had no significant effects on serotonin levels, serotonin transporter expression, or body temperature. To evaluate the effects of higher ambient temperature on methamphetamine-induced neurotoxicity, groups of mice were treated at 37°C. Overall, there was an inverse correlation between the body temperature of the animals and striatal serotonin levels. Together, the data suggest that AC927 (10 mg/kg) protects against methamphetamine-induced neurotoxicity. The reduction of methamphetamine-induced hyperthermia by AC927 may contribute to the observed neuroprotection in vivo. PMID:21130800

  11. Correlates of transient versus persistent psychotic symptoms among dependent methamphetamine users.

    PubMed

    McKetin, Rebecca; Gardner, Jonathon; Baker, Amanda L; Dawe, Sharon; Ali, Robert; Voce, Alexandra; Leach, Liana S; Lubman, Dan I

    2016-04-30

    This study examined correlates of transient versus persistent psychotic symptoms among people dependent on methamphetamine. A longitudinal prospective cohort study of dependent methamphetamine users who did not meet DSM-IV criteria for lifetime schizophrenia or mania. Four non-contiguous one-month observation periods were used to identify participants who had a) no psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient psychotic symptoms, n=85); and, (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent psychotic symptoms, n=37). Psychotic symptoms were defined as a score of 4 or greater on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content. Relative no psychotic symptoms, both transient and persistent psychotic symptoms were associated with childhood conduct disorder and comorbid anxiety disorders. Earlier onset methamphetamine use and being male were more specifically related to transient psychotic symptoms, while a family history of a primary psychotic disorder and comorbid major depression were specifically related to persistent psychotic symptoms. We conclude that there are overlapping but also distinct clinical correlates of transient versus persistent psychotic symptoms, suggesting potentially heterogeneous etiological pathways underpinning the psychotic phenomena seen amongst people who use methamphetamine. PMID:27086229

  12. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    MedlinePlus

    ... Alters Brain Structures, Impairs Mental Flexibility Methamphetamine Alters Brain Structures, Impairs Mental Flexibility Email Facebook Twitter March ... methamphetamine use, such as tobacco smoking. Can the Brain Recover? The UCLA study’s findings underscore the importance ...

  13. Methamphetamine Trends in the United States

    MedlinePlus

    ... and PSE are precursor chemicals used in the production of methamphetamine. In the CMEA, law enforcement officials ... 10 pounds or more of methamphetamine in a production cycle). Meth lab incidents in Kentucky have increased ...

  14. Methamphetamine Lab Incidents, 2004-2014

    MedlinePlus

    ... Liderazgo de la DEA Resource Center » Statistics & Facts » Methamphetamine Lab Incidents Methamphetamine Lab Incidents, 2004-2014 NOTE: These maps include all meth incidents, including labs, "dumpsites" or "chemical and glassware" ...

  15. Prenatal Methamphetamine Exposure Linked with Problems

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... a sequence of effects following prenatal exposure to cocaine, a stimulant similar to methamphetamine. Identifying such problems ...

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

    PubMed

    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 < 0.01), particularly, methamphetamine smoking (57% vs. 34%; p < 0.01). Among females (N = 158), being aged >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. PMID:19521780

  17. Methamphetamine: Putting the Brakes on Speed

    ERIC Educational Resources Information Center

    Gettig, Jacob P.; Grady, Sarah E.; Nowosadzka, Izabella

    2006-01-01

    In only recent history, illicit use of methamphetamine, once isolated to urban areas on the West Coast, has spread into rural areas of the Midwest and southern United States. Although past and current methamphetamine legislation has increased penalties for methamphetamine manufacturers and tightened restrictions on sales of known precursors, the…

  18. Methamphetamine induces the release of endothelin.

    PubMed

    Seo, Jeong-Woo; Jones, Susan M; Hostetter, Trisha A; Iliff, Jeffrey J; West, G Alexander

    2016-02-01

    Methamphetamine is a potent psychostimulant drug of abuse that increases release and blocks reuptake of dopamine, producing intense euphoria, factors that may contribute to its widespread abuse. It also produces severe neurotoxicity resulting from oxidative stress, DNA damage, blood-brain barrier disruption, microgliosis, and mitochondrial dysfunction. Intracerebral hemorrhagic and ischemic stroke have been reported after intravenous and oral abuse of methamphetamine. Several studies have shown that methamphetamine causes vasoconstriction of vessels. This study investigates the effect of methamphetamine on endothelin-1 (ET-1) release in mouse brain endothelial cells by ELISA. ET-1 transcription as well as endothelial nitric oxide synthase (eNOS) activation and transcription were measured following methamphetamine treatment. We also examine the effect of methamphetamine on isolated cerebral arteriolar vessels from C57BL/6 mice. Penetrating middle cerebral arterioles were cannulated at both ends with a micropipette system. Methamphetamine was applied extraluminally, and the vascular response was investigated. Methamphetamine treatment of mouse brain endothelial cells resulted in ET-1 release and a transient increase in ET-1 message. The activity and transcription of eNOS were only slightly enhanced after 24 hr of treatment with methamphetamine. In addition, methamphetamine caused significant vasoconstriction of isolated mouse intracerebral arterioles. The vasoconstrictive effect of methamphetamine was attenuated by coapplication of the endothelin receptor antagonist PD145065. These findings suggest that vasoconstriction induced by methamphetamine is mediated through the endothelin receptor and may involve an endothelin-dependent pathway. PMID:26568405

  19. Methamphetamine Self-Administration in Mice Decreases GIRK Channel-Mediated Currents in Midbrain Dopamine Neurons

    PubMed Central

    Sharpe, Amanda L.; Varela, Erika; Bettinger, Lynne

    2015-01-01

    Background: Methamphetamine is a psychomotor stimulant with abuse liability and a substrate for catecholamine uptake transporters. Acute methamphetamine elevates extracellular dopamine, which in the midbrain can activate D2 autoreceptors to increase a G-protein gated inwardly rectifying potassium (GIRK) conductance that inhibits dopamine neuron firing. These studies examined the neurophysiological consequences of methamphetamine self-administration on GIRK channel-mediated currents in dopaminergic neurons in the substantia nigra and ventral tegmental area. Methods: Male DBA/2J mice were trained to self-administer intravenous methamphetamine. A dose response was conducted as well as extinction and cue-induced reinstatement. In a second study, after at least 2 weeks of stable self-administration of methamphetamine, electrophysiological brain slice recordings were conducted on dopamine neurons from self-administering and control mice. Results: In the first experiment, ad libitum-fed, nonfood-trained mice exhibited a significant increase in intake and locomotion following self-administration as the concentration of methamphetamine per infusion was increased (0.0015–0.15mg/kg/infusion). Mice exhibited extinction in responding and cue-induced reinstatement. In the second experiment, dopamine cells in both the substantia nigra and ventral tegmental area from adult mice with a history of methamphetamine self-administration exhibited significantly smaller D2 and GABAB receptor-mediated currents compared with control mice, regardless of whether their daily self-administration sessions had been 1 or 4 hours. Interestingly, the effects of methamphetamine self-administration were not present when intracellular calcium was chelated by including BAPTA in the recording pipette. Conclusions: Our results suggest that methamphetamine self-administration decreases GIRK channel-mediated currents in dopaminergic neurons and that this effect may be calcium dependent. PMID:25522412

  20. Maxillary sinus manifestations of methamphetamine abuse.

    PubMed

    Faucett, Erynne A; Marsh, Katherine M; Farshad, Kayven; Erman, Audrey B; Chiu, Alexander G

    2015-01-01

    Methamphetamines are the second most commonly used illicit drug worldwide and cost the United States health-care system ∼$23.4 billion annually. Use of this drug affects multiple organ systems and causes a variety of clinical manifestations. Although there are commonly known sequelae of methamphetamine abuse such as "meth mouth," there is limited evidence regarding maxillary sinus manifestations. The following cases highlight the initial evaluation and management of two methamphetamine abusers with loculated purulent collections within the maxillary sinus as a result of methamphetamine abuse. Our aim was to delineate the otolaryngologic symptoms associated with the patients' methamphetamine abuse. Computed tomography and magnetic resonance imaging studies revealed loculated purulent collections within the maxillary sinus of probable odontogenic origin in both patients. Methamphetamine abuse leading to rampant caries and poor oral hygiene may predispose individuals for craniofacial infections and fluid collections. These cases illustrate the development of maxillary sinusitis and maxilla mucoceles that have been associated with methamphetamine use. PMID:25675268

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

    PubMed Central

    2009-01-01

    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. PMID:19445678

  2. Discriminative-Stimulus Effects of Second Generation Synthetic Cathinones in Methamphetamine-Trained Rats

    PubMed Central

    Naylor, Jennifer E.; Freeman, Kevin B.; Blough, Bruce E.; Woolverton, William L.; Huskinson, Sally L.

    2015-01-01

    Background Synthetic cathinones are beta-ketophenethylamine analogs manufactured to avoid legal restrictions placed on illicit stimulants like methamphetamine. Regulating these “emerging” designer drugs requires scientific evidence of abuse potential. Methods The present study evaluated the discriminative-stimulus effects of three synthetic cathinones, recently identified in commercial and confiscated products, in male Sprague-Dawley rats trained to discriminate methamphetamine (1.0 mg/kg) from saline under a fixed-ratio (FR) 20 schedule of food delivery. Three synthetic cathinones, 4-methyl-N-ethylcathinone (4-MEC; 1.0-8.0 mg/kg), 4-methyl-alpha -pyrrolidinopropiophenone (4-MePPP; 4.0-16.0 mg/kg), and alpha-pyrrolidinopentiophenone (alpha-PVP; 0.25-2.0 mg/kg) were tested for their ability to substitute for methamphetamine. Results Full substitution for the training dose of methamphetamine occurred at the highest doses for both 4-MePPP and alpha-PVP, and 4-MEC did not substitute at any dose tested. Conclusions The present findings show that two synthetic cathinones, 4-MePPP and alpha-PVP, produced subjective effects similar to those of methamphetamine. The synthetic cathinone, 4-MEC, did not produce subjective effects similar to those of methamphetamine with the parameters used in the current experiment. Based on findings here and by others, these three compounds warrant further tests of abuse liability. PMID:25707704

  3. Discriminative stimulus effects of NMDA, AMPA and mGluR5 glutamate receptor ligands in methamphetamine-trained rats

    PubMed Central

    Wooters, Thomas E.; Dwoskin, Linda P.; Bardo, Michael T.

    2011-01-01

    Glutamate contributes to the reinforcing and stimulant effects of methamphetamine, yet its potential role in the interoceptive stimulus properties of methamphetamine is unknown. In the current study, adult male Sprague-Dawley rats were trained to discriminate methamphetamine (1.0 mg/kg, i.p.) from saline in a standard operant discrimination task. The effects of methamphetamine (0.1-1.0 mg/kg, i.p.), the N-methyl-D-aspartate (NMDA) receptor channel blockers MK-801 (0.03-0.3 mg/kg, i.p.) and ketamine (1.0-10.0 mg/kg, i.p.), the low-affinity NMDA antagonist memantine (1.0-10 mg/kg, i.p.), the polyamine site NMDA receptor antagonist ifenprodil (1-10 mg/kg), the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1-10 mg/kg, i.p.), and the metabotropic 5 (mGluR5) receptor antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP; 1-10 mg/kg) given alone were determined in substitution tests. The effects of MK-801 (0.03 and 0.1 mg/kg), ketamine (1.0 and 3.0 mg/kg), ifenprodil (5.6 mg/kg), CNQX (5.6 mg/kg) and MPEP (5.6 mg/kg) were also tested in combination with methamphetamine to assess for alterations in the methamphetamine cue. In substitution tests, none of the test drugs generalized to the methamphetamine cue. However, ketamine and ifenprodil produced significant leftward shifts in the methamphetamine dose-response curve; pretreatment with 3 mg/kg of ketamine, for example, decreased the ED50 value for methamphetamine by half. These results suggest that blockade of the NMDA receptor augments the interoceptive stimulus properties of methamphetamine. PMID:21836462

  4. Chronic Methamphetamine Increases Alpha-Synuclein Protein Levels in the Striatum and Hippocampus but not in the Cortex of Juvenile Mice

    PubMed Central

    Butler, B.; Gamble-George, J.; Prins, P.; North, A.; Clarke, J.T; Khoshbouei, H.

    2015-01-01

    Methamphetamine is the second most widely used illicit drug worldwide. More than 290 tons of methamphetamine was synthesized in the year 2005 alone, corresponding to approximately ~3 billion 100 mg doses of methamphetamine. Drug addicts abuse high concentrations of methamphetamine for months and even years. Current reports in the literature are consistent with the interpretation that methamphetamine-induced neuronal injury may render methamphetamine users more susceptible to neurodegenerative pathologies. Specifically, chronic exposure to psychostimulants is associated with increases in striatal alpha-synuclein expression, a synaptic protein implicated in the pathogenesis of neurodegenerative diseases. This raises the question whether methamphetamine exposure affects alpha-synuclein levels in the brain. In this short report, we examined alpha-synuclein protein and mRNA levels in the striatum, hippocampus and cortex of adolescent male mice following a neurotoxic regimen of methamphetamine (24mg/kg/daily/14days). We found that methamphetamine exposure resulted in a decrease in the monomeric form of alpha-synuclein (molecular species <19 kDa), while increasing higher molecular weight alpha-synuclein species (>19 kDa) in the striatum and hippocampus, but not in the cortex. Despite the elevation of high molecular weight alpha-synuclein species (>19 kDa), there was no change in the alpha-synuclein mRNA levels in the striatum, hippocampus and cortex of mice exposed to methamphetamine. The methamphetamine-induced increase in high molecular weight alpha-synuclein protein levels might be one of the causal mechanisms or one of the compensatory consequences of methamphetamine-mediated neurotoxicity. PMID:25621291

  5. Physical Victimization of Rural Methamphetamine and Cocaine Users

    PubMed Central

    Kramer, Teresa L.; Borders, Tyrone F.; Tripathi, Shanti; Lynch, Christian; Leukefeld, Carl; Falck, Russel S.; Carlson, Robert G.; Booth, Brenda M.

    2012-01-01

    Substance use and physical violence often co-occur, but little has been published on the correlates associated with receipt of partner versus non-partner physical violence for rural users of methamphetamine and/or cocaine. In this study, participants’ substance use, depression and past-year physical victimization were assessed. In separate logistic regression models, received partner violence in females was associated with age; alcohol, cocaine and methamphetamine abuse/dependence; and number of drugs used in the past six months. In males, received non-partner violence was associated with age, cocaine abuse/dependence and being Caucasian. Findings suggest a relationship between stimulant use and received violence among rural substance users and a need for victimization screenings in settings where such individuals seek health care. PMID:22455188

  6. Methamphetamines and Pregnancy Outcomes

    PubMed Central

    Wright, Tricia E.; Schuetter, Renee; Tellei, Jacqueline; Sauvage, Lynnae

    2014-01-01

    Introduction Methamphetamine (MA) is one of the most commonly used illicit drugs in pregnancy, yet studies on MA-exposed pregnancy outcomes have been limited because of retrospective measures of drug use, lack of control for confounding factors: other drug use, including tobacco; poverty; poor diet; and lack of prenatal care. This study presents prospective collected data on MA use and birth outcomes, controlling for most confounders. Materials and Methods This is a retrospective cohort study of women obtaining prenatal care from a clinic treating women with substance use disorders, on whom there are prospectively obtained data on MA and other drug use, including tobacco. MA-exposed pregnancies were compared with non-MA exposed pregnancies as well as non-drug exposed pregnancies, using univariate and multivariate analysis to control for confounders. Results One hundred forty-four infants were exposed to MA during pregnancy, 50 had first trimester exposure only, 45 had continuous use until the second trimester, 29 had continuous use until the third trimester, but were negative at delivery and 20 had positive toxicology at delivery. There were 107 non MA-exposed infants and 59 infants with no drug exposure. Mean birth weights were the same for MA-exposed and non-exposed infants (3159 g vs. 3168 g p=0.9), though smaller than those without any drug exposure (3159 vs. 3321 p=0.04), Infants with positive toxicology at birth (meconium or urine) were smaller than infants with first trimester exposure only (2932 g vs. 3300 g p=0.01). Gestation was significantly shorter among the MA-exposed infants compared to non-exposed infants (38.5 vs. 39.1 weeks p=0.045) and those with no drug exposure (38.5 vs. 39.5 p=0.0011), The infants with positive toxicology at birth had a clinically relevant shortening of gestation (37.3 weeks vs. 39.1 p=0.0002). Conclusions MA use during pregnancy is associated with shorter gestational ages and lower birth weight, especially if used continuously

  7. “High On My Own Supply”: Correlates of Drug Dealing among Heterosexually-identified Methamphetamine Users

    PubMed Central

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

    2011-01-01

    Although rates of methamphetamine use continue to increase throughout the United States, little is known about the individuals who sell methamphetamine at the street level. This exploratory study examined the prevalence and correlates of drug-dealing behavior in a sample of 404 heterosexually-identified methamphetamine users who were participants in a sexual risk reduction intervention in San Diego, CA. Twenty-nine percent of participants (N = 116) reported “dealing” methamphetamine in the past two months. In a multivariate logistic regression, methamphetamine dealing was associated with being male (OR = 1.99; 95% CI 1.16 – 3.39), younger age (OR = 1.87 per year; 95% CI 1.10 – 3.17), more frequent use of methamphetamine (OR = 2.69; 95% CI 1.59 – 4.57), injecting methamphetamine (OR = 3.10; 95% CI 1.79 – 5.37), and higher hostility scores (OR = 1.07 per unit increase; 95% CI 1.01 – 1.13). These characteristics, particularly intensity of drug use and hostility, may be associated with greater resistance to drug treatment and lower success in treatment programs. PMID:21999496

  8. Methamphetamine Use and Oral Health

    MedlinePlus

    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 names: “meth,” “speed,” “ice,” “chalk,” “crank,” “fire,” “glass,” “crystal” and “tina.” It is ...

  9. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....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... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Methamphetamine test system. 862.3610 Section...

  10. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....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... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methamphetamine test system. 862.3610 Section...

  11. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....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... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methamphetamine test system. 862.3610 Section...

  12. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....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... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Methamphetamine test system. 862.3610 Section...

  13. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....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... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methamphetamine test system. 862.3610 Section...

  14. Methamphetamine Use and Sexual Risk Behavior among High School Students in Cape Town, South Africa

    ERIC Educational Resources Information Center

    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:…

  15. Need for Methamphetamine Programming in Extension Education

    ERIC Educational Resources Information Center

    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…

  16. Methamphetamine Use: Hazards and Social Influences.

    ERIC Educational Resources Information Center

    Wermuth, Laurie

    2000-01-01

    Presents data on methamphetamine use in the United States and the economic and social pressures that may partially explain expanded methamphetamine use. Recommends a policy response that utilizes a public health approach, including prevention campaigns, harm-reduction outreach and treatment approaches, and pharmacologic and abstinence-based drug…

  17. Behavioral and growth effects induced by low dose methamphetamine administration during the neonatal period in rats.

    PubMed

    Williams, Michael T; Moran, Mary S; Vorhees, Charles V

    2004-01-01

    The investigation of methamphetamine exposure during neonatal development in rats has demonstrated that long-term spatial learning deficits are induced. A previous dose-response study showed that administration of 5 mg/kg methamphetamine, four times daily from postnatal days 11 to 20 produced these deficits, although the effects were not as severe as at higher doses of 10 or 15 mg/kg. This study examined concentrations of methamphetamine at or below 5mg/kg given over the same period of time. Five different concentrations of methamphetamine (i.e., 5, 2.5, 1.25, 0.625, or 0) were administered every 2 h four times daily from postnatal days 11 to 20. Body weights, zero maze performance, and Morris water maze learning were examined. A dose-dependent decrease in body weight was observed during the period of methamphetamine administration and these lower weights continued throughout adulthood for the 5, 2.5, and 1.25 mg/kg concentrations, although the adult decreases were negligible. No differences were noted in the zero maze. In the Morris water maze during the acquisition period, dose-dependent differences in spatial orientation were seen, however non-dose related deficits were observed for other parameters. During the shifted platform phase ("reversal"), a similar dose-dependent difference in spatial orientation was observed, although no other effects were noted during this phase. Females performed worse than males regardless of treatment or the phase of learning in the Morris water maze. These data suggest that even lower doses of methamphetamine can alter learning and memory in adulthood, although with less consistent results than with doses higher than 5 mg/kg/dose. These data would caution against even casual use of methamphetamine by women during pregnancy since even low doses could alter the ability of the child to learn. PMID:15380827

  18. Methamphetamine Use and Violent Behavior: User Perceptions and Predictors

    PubMed Central

    Brecht, Mary-Lynn; Herbeck, Diane

    2015-01-01

    This study describes the extent to which methamphetamine users perceive that their methamphetamine use has resulted in violent behavior, and describes the level of self-reported prevalence of specific violent criminal behaviors irrespective of methamphetamine use. Predictors of these two violence-related indicators, in terms of potential correlates from substance use history, criminal history, and health risk domains are examined. Data are from extensive interviews of 350 methamphetamine users who received substance use treatment in a large California county. A majority (56%) perceived that their methamphetamine use resulted in violent behavior; 59% reported specific violent criminal behaviors. For more than half of those reporting violent criminal behavior, this behavior pattern began before methamphetamine initiation. Thus, for a subsample of methamphetamine users, violence may be related to factors other than methamphetamine use. Users' perceptions that their methamphetamine use resulted in violence appears strongest for those with the most severe methamphetamine-related problems, particularly paranoia. PMID:26594058

  19. Neural Correlates of Craving in Methamphetamine Abuse

    PubMed Central

    Shahmohammadi, Fanak; Golesorkhi, Mehrshad; Riahi Kashani, Mohammad Mansour; Sangi, Mehrdad; Yoonessi, Ahmad; Yoonessi, Ali

    2016-01-01

    Introduction: Methamphetamine is a powerful psychostimulant that causes significant neurological impairments with long-lasting effects and has provoked serious international concerns about public health. Denial of drug abuse and drug craving are two important factors that make the diagnosis and treatment extremely challenging. Here, we present a novel and rapid noninvasive method with potential application for differentiation and monitoring methamphetamine abuse. Methods: Visual stimuli comprised a series of images with neutral and methamphetamine-related content. A total of 10 methamphetamine abusers and 10 age-gender matched controls participated in the experiments. Event-related potentials (ERPs) were recorded and compared using a time window analysis method. The ERPs were divided into 19 time windows of 100 ms with 50 ms overlaps. The area of positive sections below each window was calculated to measure the differences between the two groups. Results: Significant differences between two groups were observed from 250 to 500 ms (P300) in response to methamphetamine-related visual stimuli and 600 to 800 ms in response to neutral stimuli. Conclusion: This study presented a novel and noninvasive method based on neural correlates to discriminate healthy individuals from methamphetamine drug abusers. This method can be employed in treatment and monitoring of the methamphetamine abuse. PMID:27563415

  20. Methamphetamine. Stimulant of the 1990s?

    PubMed Central

    Derlet, R. W.; Heischober, B.

    1990-01-01

    During the past several years, the use of a smokable form of methamphetamine hydrochloride called "ice" has increased rapidly. The heaviest use has occurred on the West Coast and in Hawaii. Many regional emergency departments treat more methamphetamine users than cocaine-intoxicated patients. The ease of synthesis from inexpensive and readily available chemicals makes possible the rampant abuse of a dangerous drug that can produce a euphoria similar to that induced by cocaine. Clinicians should be familiar with the medical effects and treatment of acute methamphetamine toxicity. PMID:2293467

  1. The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse

    PubMed Central

    Beardsley, Patrick M.; Shelton, Keith L.; Hendrick, Elizabeth; Johnson, Kirk W.

    2010-01-01

    Stress and renewed contact with drug (a “slip”) have been linked to persisting relapse of methamphetamine abuse. Human brain microglial activation has been linked with methamphetamine abuse, and inhibitors of glial cell activation, certain phosphodiesterase (PDE) inhibitors, and glial cell derived neurotrophic factor (GDNF) have been reported to modulate drug abuse effects. Our objective was to determine whether the glial cell attenuator, 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine (AV411, ibudilast), a non-selective PDE inhibitor and promoter of GDNF, could reduce stress- and methamphetamine prime-induced reinstatement of methamphetamine-seeking behavior. Male Long-Evans hooded rats were trained to lever press reinforced with 0.1 mg/kg i.v. methamphetamine infusion according to fixed-ratio 1 (FR1) reinforcement schedules during daily, 2-h experimental sessions. After performance had stabilized, lever pressing was extinguished for 12 consecutive sessions and doses of 0 (vehicle), 2.5 and 7.5 mg/kg AV411 were then administered intraperitoneally b.i.d. on the last two days of extinction and then once on the testday to separate groups of 12 rats. During testing, the rats were given 15 min of intermittent footshock or a 1 mg/kg i.p. methamphetamine prime followed by a 2-h reinstatement test session. AV411 significantly reduced response levels of footshock-induced (2.5 and 7.5 mg/kg) and prime-induced (7.5 mg/kg) reinstatement of extinguished methamphetamine-maintained responding. AV411 has properties consistent with the ability to attenuate relapse precipitated by stress and methamphetamine “slips” during abstinence. These results thus reinforce interest in atypical neurobiological mechanisms which could be exploited for developing novel medications for treating drug abuse disorders. PMID:20399770

  2. Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

    MedlinePlus

    ... to methamphetamine damages dopamine and serotonin terminals on neurons in the striatum, reducing levels of these neurotransmitters and impairing communication between neurons in this brain area. Past studies have shown ...

  3. Surgical Intervention for Penile Methamphetamine Injections

    PubMed Central

    Gaither, Thomas W.; Osterberg, E. Charles; Awad, Mohannad A.; Breyer, Benjamin N.

    2015-01-01

    Methamphetamine is a central nervous system stimulant and is the second most commonly used illicit drug after cannabis. Methamphetamine use for sexual pleasure is well documented. In this case report, we describe two cases presenting to our urban county hospital associated with complications related to penile injection of methamphetamine. Both patients developed penile abscesses and required urgent surgical incision and drainage. Penile abscesses represent a rare complication associated with IV drug administration into the penile corpora. Resultant penile abscesses require broad-spectrum antibiotics and surgical drainage. Further understanding of methamphetamine abuse along with the role it plays in sexual enhancement would be an invaluable addition to understanding of the rationale behind this self-administered stimulant. Drainage of penile abscesses associated with IV drug users may be hazardous to healthcare providers who are at risk from a needle stick injury. PMID:26451272

  4. Palmoplantar pustules and osteoarticular pain in a 42-year-old woman.

    PubMed

    Zuo, Rena C; Schwartz, Daniella M; Lee, Chyi-Chia Richard; Anadkat, Milan J; Cowen, Edward W; Naik, Haley B

    2015-03-01

    Key teaching points • Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is characterized by distinctive osteoarticular manifestations and a spectrum of neutrophilic dermatoses. • The most common dermatologic manifestations include palmoplantar pustulosis, acne conglobata, and acne fulminans. • SAPHO syndrome should be considered in patients presenting osteoarticular pain, particularly involving the anterior chest wall and/or spine, and neutrophilic skin lesions. PMID:25127881

  5. Methamphetamine Vaccines: Improvement through Hapten Design.

    PubMed

    Collins, Karen C; Schlosburg, Joel E; Bremer, Paul T; Janda, Kim D

    2016-04-28

    Methamphetamine (MA) addiction is a serious public health problem, and current methods to abate addiction and relapse are currently ineffective for mitigating this growing global epidemic. Development of a vaccine targeting MA would provide a complementary strategy to existing behavioral therapies, but this has proven challenging. Herein, we describe optimization of both hapten design and formulation, identifying a vaccine that elicited a robust anti-MA immune response in mice, decreasing methamphetamine-induced locomotor activity. PMID:27054372

  6. The neurobiology of methamphetamine induced psychosis

    PubMed Central

    Hsieh, Jennifer H.; Stein, Dan J.; Howells, Fleur M.

    2014-01-01

    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 MAP as a model for schizophrenia. PMID:25100979

  7. METHAMPHETAMINE: HERE WE GO AGAIN?

    PubMed Central

    Maxwell, Jane Carlisle; Brecht, Mary-Lynn

    2011-01-01

    Following more than two decades of generally increasing trends in the use and abuse of methamphetamine in certain parts of the country, prevalence indicators for the drug began to decrease in the mid-2000’s—but was this decrease signaling the end of the “meth problem”? This paper has compiled historical and recent data from supply and demand indicators to provide a broader context within which to consider the changes in trends over the past half decade. Data suggest supply-side accommodation to changes in precursor chemical restrictions, with prevalence indicators beginning to attenuate in the mid-2000’s and then increasing again by 2009–2010. Results support the need for continuing attention to control and interdiction efforts appropriate to the changing supply context and to continuing prevention efforts and increased number of treatment programs. PMID:21875772

  8. What You Need to Know about Drugs: Methamphetamines

    MedlinePlus

    ... Here's Help White House Lunch Recipes What You Need to Know About Drugs: Methamphetamines KidsHealth > For Kids > What You Need to Know About Drugs: Methamphetamines Print A A A Text Size en español ...

  9. The Methamphetamine Home: Psychological Impact on Preschoolers in Rural Tennessee

    ERIC Educational Resources Information Center

    Asanbe, Comfort B.; Hall, Charlene; Bolden, Charles D.

    2008-01-01

    Context: A growing number of children reside with methamphetamine-abusing parents in homes where the illicit drug is produced. Yet, the effects of a methamphetamine environment on psychological child outcome are still unknown. Purpose: To examine whether preschoolers who lived in methamphetamine-producing homes are at increased risk for developing…

  10. Methamphetamine

    MedlinePlus

    ... use can quickly lead to addiction. It causes medical problems including Making your body temperature so high that you pass out Severe itching "Meth mouth" - broken teeth and dry mouth Thinking and emotional problems NIH: ...

  11. Methamphetamine

    MedlinePlus

    ... OPERATIONS Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip DRUG INFO Drug Fact Sheets ... Operations Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip Drug Info Drug Fact Sheets ...

  12. Methamphetamine

    MedlinePlus

    ... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... excessive tiredness slow or difficult speech seizures motor tics or verbal tics believing things that are not ...

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

    PubMed Central

    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 < .01, suggesting that creatine increased phosphocreatine levels. Also, a reduction in methamphetamine

  14. Pharmacotherapy of methamphetamine addiction: an update.

    PubMed

    Elkashef, Ahmed; Vocci, Frank; Hanson, Glen; White, Jason; Wickes, Wendy; Tiihonen, Jari

    2008-01-01

    Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies. PMID:19042205

  15. Pharmacotherapy of Methamphetamine Addiction: An Update

    PubMed Central

    Elkashef, Ahmed; Vocci, Frank; Hanson, Glen; White, Jason; Wickes, Wendy; Tiihonen, Jari

    2008-01-01

    Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies. PMID:19042205

  16. The War on Drugs: Methamphetamine, Public Health, and Crime

    PubMed Central

    Dobkin, Carlos; Nicosia, Nancy

    2010-01-01

    In mid-1995, a government effort to reduce the supply of methamphetamine precursors successfully disrupted the methamphetamine market and interrupted a trajectory of increasing usage. The price of methamphetamine tripled and purity declined from 90 percent to 20 percent. Simultaneously, amphetaminerelated hospital and treatment admissions dropped 50 percent and 35 percent, respectively. Methamphetamine use among arrestees declined 55 percent. Although felony methamphetamine arrests fell 50 percent, there is no evidence of substantial reductions in property or violent crime. The impact was largely temporary. The price returned to its original level within four months; purity, hospital admissions, treatment admissions, and arrests approached preintervention levels within eighteen months. (JEL I12, K42) PMID:20543969

  17. Functional and Structural Brain Changes Associated with Methamphetamine Abuse

    PubMed Central

    Jan, Reem K.; Kydd, Rob R.; Russell, Bruce R.

    2012-01-01

    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. PMID:24961256

  18. Swimming exercise attenuates psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats

    PubMed Central

    Damghani, Fatemeh; Bigdeli, Imanollah; Miladi-Gorji, Hossein; Fadaei, Atefeh

    2016-01-01

    Objective(s): This study evaluated the effect of swimming exercise during spontaneous methamphetamine (METH) withdrawal on the anxiety, depression, obsessive-compulsive disorder (OCD) and voluntary METH consumption in METH-dependent rats. Materials and Methods: Male Wistar rats were repeatedly administered with bi-daily doses of METH (2 mg/kg, subcutaneous) over a period of 14 days. Exercised rats were submitted to swimming sessions (45 min/day, five days per week, for 14 days) during spontaneous METH-withdrawal. Then, all animals were tested for the assessment of anxiety by using the elevated plus-maze (EPM), the grooming behaviors (OCD), and depression using forced swimming test (FST) and voluntary METH consumption using a two-bottle choice (TBC) paradigm for the assessment of craving. Results: The results showed that the swimmer METH-withdrawn rats exhibited an increase in EPM open arm time and entries and a reduction of immobility and grooming behaviors compared with the sedentary METH groups. Also, voluntary METH consumption was less in the swimmer METH-withdrawn rats than the sedentary METH groups throughout 5–8 days. Conclusion: This study showed that regular swimming exercise reduced voluntary METH consumption in animal models of craving by reducing anxiety, OCD, and depression in the METH-withdrawn rats. Thus, physical training may be ameliorating some of the withdrawal behavioral consequences of METH. PMID:27482339

  19. [Genetic vulnerability of methamphetamine dependence].

    PubMed

    Moriya, Yuki; Kasahara, Yoshiyuki; Sora, Ichiro

    2013-08-01

    Methamphetamine (METH) dependence show strong familial and genetic influences in family and twin studies. METH exerts its reinforcing effects by modulating monoaminergic transmission, of which dopamine is supposed to be important. Previously, experimental animals were being used to identify mechanisms of action of METH that are related to its abuse and toxicity, and genetic mouse models have also been used to define genes that may predict risk for the development of drug addiction. We found that genetic variances of dopamine transporter, dopamine receptor, micro-opioid receptor, serotonin 1A receptor, serotonin 6 receptor, and adenosine 2A adenosine receptor could be vulnerability factors for METH dependence or psychosis in the Japanese population. Genetic analysis with a genome-wide association study (GWAS)-based approach has been successful for investigating the genetic influences of METH dependence and other complex features. Collaborative studies with JGIDA and NIDA/NIH have obtained the results that the genetic vulnerability to METH dependence contributes to other major drug addiction. The genetic studies for METH dependence might help to identify the risk of individuals and to develop treatments that take advantage of individual genetic information in the future. PMID:25069251

  20. Modafinil for the Treatment of Methamphetamine Dependence

    PubMed Central

    Anderson, Ann L.; Li, Shou-Hua; Biswas, Kousick; McSherry, Frances; Holmes, Tyson; Iturriaga, Erin; Kahn, Roberta; Chiang, Nora; Beresford, Thomas; Campbell, Jan; Haning, William; Mawhinney, Joseph; McCann, Michael; Rawson, Richard; Stock, Christopher; Weis, Dennis; Yu, Elmer; Elkashef, Ahmed M.

    2011-01-01

    Aim Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo. Methods This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200mg, and 70 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine. Results Regression analysis showed no significant difference between either modafinil group (200 or 400mg) and placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (>85% urines modafinil +, N=36), and the lower three quartiles of modafinil 200 and 400mg groups (N=106). Conclusions Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication. PMID:21840138

  1. Neurobehavioral Effects from Developmental Methamphetamine Exposure.

    PubMed

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

    2016-01-01

    Intrauterine methamphetamine exposure adversely affects the neurofunctional profile of exposed children, leading to a variety of higher order cognitive deficits, such as decreased attention, reduced working-memory capability, behavioral dysregulation, and spatial memory impairments (Kiblawi et al. in J Dev Behav Pediatr 34:31-37, 2013; Piper et al. in Pharmacol Biochem Behav 98:432-439 2011; Roussotte et al. in Neuroimage 54:3067-3075, 2011; Twomey et al. in Am J Orthopsychiatry 83:64-72, 2013). In animal models of developmental methamphetamine, both neuroanatomical and behavioral outcomes critically depend on the timing of methamphetamine administration. Methamphetamine exposure during the third trimester human equivalent period of brain development results in well-defined and persistent wayfinding and spatial navigation deficits in rodents (Vorhees et al. in Neurotoxicol Teratol 27:117-134, 2005, Vorhees et al. in Int J Dev Neurosci 26:599-610, 2008; Vorhees et al. in Int J Dev Neurosci 27:289-298, 2009; Williams et al. in Psychopharmacology (Berl) 168:329-338, 2003b), whereas drug delivery during the first and second trimester equivalents produces no such effect (Acuff-Smith et al. in Neurotoxicol Teratol 18:199-215, 1996; Schutova et al. in Physiol Res 58:741-750, 2009a; Slamberova et al. in Naunyn Schmiedebergs Arch Pharmacol 380:109-114, 2009, Slamberova et al. in Physiol Res 63:S547-S558, 2014b). In this review, we examine the impact of developmental methamphetamine on emerging neural circuitry, neurotransmission, receptor changes, and behavioral outcomes in animal models. The review is organized by type of effects and timing of drug exposure (prenatal only, pre- and neonatal, and neonatal only). The findings elucidate functional patterns of interconnected brain structures (e.g., frontal cortex and striatum) and neurotransmitters (e.g., dopamine and serotonin) involved in methamphetamine-induced developmental neurotoxicity. PMID:26520437

  2. Identifying methamphetamine exposure in children

    PubMed Central

    Castaneto, Marisol S.; Barnes, Allan J.; Scheidweiler, Karl B.; Schaffer, Michael; Rogers, Kristen K.; Stewart, Deborah; Huestis, Marilyn A.

    2013-01-01

    Introduction Methamphetamine (MAMP) use, distribution and manufacture remain a serious public health and safety problem in the United States, and children environmentally exposed to MAMP face a myriad of developmental, social and health risks, including severe abuse and neglect necessitating child protection involvement. It is recommended that drug-endangered children receive medical evaluation and care with documentation of overall physical and mental conditions and have urine drug testing.1 The primary aim of this study was to determine the best biological matrix to detect MAMP, amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA) in environmentally exposed children. Method 91 children, environmentally exposed to household MAMP intake, were medically evaluated at the Child and Adolescent Abuse Resource and Evaluation (CAARE) Diagnostic and Treatment Center at the University of California, Davis (UCD) Children's Hospital. MAMP, AMP, MDMA, MDA and MDEA were quantified in urine and oral fluid (OF) by gas chromatography mass spectrometry (GCMS) and in hair by liquid chromatography tandem mass spectrometry (LCMSMS). Results Overall drug detection rates in OF, urine and hair were 6.9%, 22.1% and 77.8%, respectively. Seventy children (79%) tested positive for 1 or more drugs in 1 or more matrices. MAMP was the primary analyte detected in all 3 biological matrices. All positive OF (n=5) and 18 of 19 positive urine specimens also had a positive hair test. Conclusion Hair analysis offered a more sensitive tool for identifying MAMP, AMP and MDMA environmental exposure in children than urine or OF testing. A negative urine, or hair test does not exclude the possibility of drug exposure, but hair testing provided the greatest sensitivity for identifying drug-exposed children. PMID:24263642

  3. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  4. Methamphetamine causes acute hyperthermia-dependent liver damage

    PubMed Central

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-01-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  5. Differentiating Characteristics of Juvenile Methamphetamine Users

    ERIC Educational Resources Information Center

    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…

  6. Methamphetamine Exposure: A Rural Early Intervention Challenge

    ERIC Educational Resources Information Center

    Lester, Barry M.; Arria, Amelia M.; Derauf, Christian; Grant, Penny; LaGasse, Linda; Newman, Elana; Shah, Rizwan Z.; Stewart, Sara; Wouldes, Trecia

    2006-01-01

    In the Infant Development, Environment and Lifestyle (IDEAL) Study of methamphetamine (MA) effects on children, the authors screened approximately 27,000 newborn infants for MA exposure, and from that pool derived a sample of in utero MA-exposed children as well as a comparison group matched for other drug use and other factors. IDEAL measures…

  7. Association between VNTR Polymorphism in Promoter Region of Prodynorphin (PDYN) Gene and Methamphetamine Dependence

    PubMed Central

    Saify, Khyber; Saadat, Mostafa

    2015-01-01

    AIM: Prodynorphin (PDYN; OMIM: 131340) is the precursor of the dynorphin related peptides which plays an important role in drug abuse. Previous studies have been shown that the expression of PDYN is regulated by a genetic polymorphism of VNTR in the promoter region of the gene. MATERIALS AND METHODS: The present case-control study was performed on 52 (41 males, 11 females) methamphetamine dependence patients and 635 (525 males, 110 females) healthy blood donors frequency matched with the patients according to age and gender, as a control group was participated in the study. RESULTS: The genotypes of VNTR PDYN polymorphism were determined using PCR method. The HL (OR = 1.22, 95%CI: 0.67-2.20, P = 0.500) and LL (OR = 0.86, 95%CI: 0.28-2.57, P = 0.792) genotypes does not alter the risk of methamphetamine dependence, in comparison with the HH genotypes. CONCLUSION: The present study revealed no association between the VNTR polymorphism in the promoter region of the PDYN gene and methamphetamine dependence risk.

  8. HIV Prevalence and Risk among Heterosexual Methamphetamine Injectors in California

    PubMed Central

    Kral, Alex H.; Lorvick, Jennifer; Martinez, Alexis; Lewis, Megan A.; Orr, Alexander; Anderson, Rachel; Flynn, Neil; Bluthenthal, Ricky N.

    2013-01-01

    This CDC-funded study compares HIV prevalence and risk behavior among heterosexual methamphetamine (n=428) and non-methamphetamine (n=878) injectors in California, USA during 2001–2003. While HIV was not highly prevalent among methamphetamine injectors (3%), sexual and injection risk behaviors were highly prevalent (ranging from 21% to 72%). In multivariate analyses, methamphetamine injectors had higher odds than non-methamphetamine injectors of unprotected vaginal intercourse and sex with five or more sexual partners in the past six months, and of distributive and receptive syringe sharing in the past thirty days. There was no significant difference in HIV sero-status by methamphetamine use. Suggestions are made for designing HIV prevention programs. PMID:21391786

  9. Against professional advice: treatment attrition among pregnant methamphetamine users

    PubMed Central

    Lindsay, Brianna; Albrecht, Jennifer; Terplan, Mishka

    2011-01-01

    Pregnant methamphetamine users who leave substance use treatment against professional advice may be at risk of poorer health outcomes. To examine the hypothesis that methamphetamine use during pregnancy may be associated with leaving substance use treatment against professional advice, the 2006 Treatment Episode Data Set was analyzed. A logistic regression adjusting for age, race, service setting, prior substance abuse treatment, criminal justice referral, and education was conducted. Inclusion criteria were met by 18,688 pregnant admissions; 26.4% identified methamphetamines as their primary substance of use. Frequency of use was identified as an effect modifier, therefore results were stratified by less than weekly use and weekly or more use. Methamphetamine use was significantly associated with leaving treatment against professional advice regardless of usage level. However, the odds of leaving treatment were greater among women using methamphetamine less than weekly. Further investigation into this association may be warranted due to the complications that may result from methamphetamine use during pregnancy. PMID:24474856

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

    PubMed

    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. PMID:26871405

  11. A cluster of trace-concentration methamphetamine identifications in racehorses associated with a methamphetamine-contaminated horse trailer: A report and analysis.

    PubMed

    Brewer, Kimberly; Shults, Theodore F; Machin, Jacob; Kudrimoti, Sucheta; Eisenberg, Rodney L; Hartman, Petra; Wang, Caroline; Fenger, Clara; Beaumier, Pierre; Tobin, Thomas

    2016-08-01

    Three low concentration methamphetamine "positive" tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed. PMID:27493286

  12. Methamphetamine-induced dopaminergic deficits and refractoriness to subsequent treatment.

    PubMed

    Hanson, Jarom E; Birdsall, Elisabeth; Seferian, Kristi S; Crosby, Marcus A; Keefe, Kristen A; Gibb, James W; Hanson, Glen R; Fleckenstein, Annette E

    2009-04-01

    Repeated high-dose methamphetamine administrations can cause persistent dopaminergic deficits. As individuals abusing methamphetamine are often exposed to recurrent high-dose administration, the impact of its repeated exposure merits investigation. Accordingly, rats were pretreated with repeated high-dose injections of methamphetamine, and subsequently "challenged" with the same neurotoxic regimen 7 or 30 days later. Results revealed that the initial methamphetamine treatment caused persistent deficits in striatal dopamine levels, dopamine transporter function, and vesicular monoamine transporter-2 function. The subsequent methamphetamine challenge treatment was without further persistent effects on these parameters, as assessed 7 days after the challenge, regardless of the interval (7 or 30 days) between the initial and challenge drug exposures. Similarly, a methamphetamine challenge treatment administered 7 days after the initial drug treatment was without further acute effect on dopamine transporter or VMAT-2 function, as assessed 1 h later. Thus, this study describes a model of resistance, possibly explained by: 1) the existence of dopaminergic neurons that are a priori refractory to deficits caused by methamphetamine; 2) the existence of dopaminergic neurons made persistently resistant consequent to a neurotoxic methamphetamine exposure; and/or 3) altered activation of post-synaptic basal ganglia systems necessary for the elaboration of methamphetamine-induced dopamine neurotoxicity. PMID:19326567

  13. Leave methamphetamine to be alive--Part II.

    PubMed

    Islam, Mohammed Nasimul; Khan, Jesmine; Jaafar, Hasnan

    2009-04-01

    Series of experiments have been completed with Methamphetamine (MA). Some were with the higher, medium or lower duration of MA administration and some were with acute or chronic doses. Whatever may be the dose or duration the ultimate result came out with the further establishment of cardio-toxic effect of this drug. Cardiovascular symptoms related to MA toxicity include chest pain, palpitations, dyspnoea, hypertension, tachycardia, atrial and ventricular arrhythmias, and myocardial ischemia. MA abusers often go through a repeated pattern of frequent drug administrations followed by a period of abstinence. Previous studies have focused largely upon the chronic effect of MA intake to major organs, such as the brains and the heart, by using animal experiments. However, there is a lack of research into the effects of acute dose of MA, especially pertaining to the heart. To clarify the effect of MA on myocardium, 22 male Wister rats aged six weeks were divided into MA, Placebo (P) and Control (C) group were examined following single intraperitoneal administration of MA at a dose of 50 mg/kg body weight. Normal saline was similarly injected in P group. Light microscopic changes was seen in the myocardium of MA treated group including cellular infiltration, with clusters of macrophage-like cells having large nuclei and little cytoplasm evident in the sub-endocardium region. There were presence of few macrophages, leucocytes, and spindle-like fibroblasts. Bringing in to account of cardiac changes by a single dose of MA, slogan should be voiced out to leave methamphetamine. PMID:19345604

  14. Comparative Study of the Activity of Brain Behavioral Systems in Methamphetamine and Opiate Dependents

    PubMed Central

    Alemikhah, Marjan; Faridhosseini, Farhad; Kordi, Hassan; Rasouli-Azad, Morad; Shahini, Najmeh

    2016-01-01

    Background: Substance dependency is a major problem for the general health of a society. Different approaches have investigated the substance dependency in order to explain it. Gray’s reinforcement sensitivity theory (RST) is an advanced and important neuropsychological theory in this area. Objectives: The aim of this study was to compare three systems of the revised reinforcement sensitivity theory the behavioral activation system (r-BAS), the revised behavioral inhibition system (r-BIS), and the revised fight/flight/freezing system (r-FFFS) between patients dependent on methamphetamine and opiates, and a group of controls. Patients and Methods: This research was a causal-comparative study that was conducted in the first six months of 2012. The population of the study was males of Mashhad city, who were dependent on methamphetamine or opiates, and ruling out psychotic disorders and prominent Axis II. Twenty-five people were selected by the convenient sampling method. Also, 25 non-dependent people from the patients’ relatives were selected and matched for the variables of age, gender, and education to participate in this study. Participants were evaluated using a structured clinical interview (SCID) for DSM-IV, demographic questionnaire information, and a Jackson-5 questionnaire (2009). Data were analyzed by Chi-square, K-S, and independent t-test. Results: The methamphetamine dependent group had a higher sensitivity in the r-BAS, r-BIS, and the r-Fight and r-Freezing systems compared to the control group (P < 0.05). However, there was no significant difference in r-Flight between the two groups (P > 0.05). “The scores of r-BIS were also significantly higher in the methamphetamine-dependent group than the opioid-dependent and control groups. For the r-Fight variable, the methamphetamine-dependent group was higher than the opioid-dependent group”. Conclusions: The personality patterns of patients dependent on methamphetamines were different from the controls

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

    PubMed

    Sherman, Susan G; Sutcliffe, Catherine; Srirojn, Bangorn; Latkin, Carl A; Aramratanna, Apinun; Celentano, David D

    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 3-, 6-, 9-, and 12 months. Both conditions consisted of seven, 2h, 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 vs. 53% at 12 months, p<0.0001) and significant increase in consistent condom use (32% baseline vs. 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 effective means of

  16. Neurologic manifestations of chronic methamphetamine abuse

    PubMed Central

    Rusyniak, Daniel E.

    2011-01-01

    Summary Chronic methamphetamine abuse has devastating effects on the central nervous system. The degree to which addicts will tolerate the dysfunction in the way they think, feel, move, and even look, is a powerful testimony to the addictive properties of this drug. While the mechanisms behind these disorders are complex, at their heart they involve the recurring increase in the concentrations of central monoamines with subsequent dysfunction in dopaminergic neurotransmission. The mainstay of treatment for the problems associated with chronic methamphetamine abuse is abstinence. However, by recognizing the manifestations of chronic abuse, clinicians will be better able to help their patients get treatment for their addiction and to deal with the neurologic complications related to chronic abuse. PMID:21803215

  17. METHAMPHETAMINE: WHERE WILL THE STAMPEDE TAKE US?

    PubMed

    Sullivan, Danny; McDonough Michael

    2015-09-01

    Methamphetamine, particularly "ice", currently preoccupies the media and there are a range of government initiatives which seem to follow media interest. We summarise the progress of government attention, briefly review health concerns associated with methamphetamine use, and summarise the evidence for treatments, including psychosocial interventions and medications. Amid concerns that governments will seek to fund any promising initiative in order to be perceived as responding to an epidemic, we caution that existing treatments should not be abandoned in favour of untested but potentially attractive treatments. Harm reduction and outpatient psychological treatments remain the mainstay of drug treatment programs and may be more cost-effective and broader-reaching than inpatient, medication-based detoxifications. PMID:26554196

  18. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. PMID:26070758

  19. Dual epidemics of syphilis and methamphetamine use among drug users in Shandong Province of China.

    PubMed

    Liao, Meizhen; Kang, Dianmin; Tao, Xiaorun; Li, Jie; Qian, Yuesheng; Wang, Guoyong; Jiang, Baofa; Bi, Zhenqiang; Jia, Yujiang

    2013-01-01

    We assessed the types of drugs, the prevalence of HIV, syphilis, and its correlates among Shandong's drug users in China. Two consecutive cross-sectional surveys in 2009 and 2010 provided demographics, types of drugs, sexual and drug-use behaviors, and HIV-related services. Of the 1320 unique, eligible participants, 81.1% were male, two-thirds <35 years of age, 13.0% non-Shandong residents; in the past year, majority (96.4%) reported ever using methamphetamine, 3.4% using heroin, 8.6% using ≥2 types of these drugs and 8.0% injecting drugs, 63.8% having commercial sex. HIV and syphilis prevalence were 0.2% and 8.3%, respectively. In multivariable logistic regression analysis, syphilis was independently associated with female, non-Shandong residents, higher levels of education, and 2010. Synthetic drugs, especially methamphetamine, have become the predominant sources of drug addiction. The emerging epidemic of syphilis potentially driven by methamphetamine use underscored the urgency to implement an effective sex and substance use-related intervention. PMID:23394142

  20. Gender difference in hippocampal volume reduction among abstinent methamphetamine users

    PubMed Central

    Du, Jiang; Quan, Meina; Zhuang, Wenxu; Zong, Na; Jiang, Haifeng; Kennedy, David N.; Harrington, Amy; Ziedonis, Douglas; Fan, Xiaoduo; Zhao, Min

    2015-01-01

    Background and Aims Growing evidence suggests abnormalities in brain morphology including hippocampal structure in patients with methamphetamine (MA) dependence. Yet little is known about the possible gender difference. This study was performed to examine hippocampal volume in abstinent male and female MA users, and to further explore its relationship with cognitive function. Methods 27 abstinent MA users (19 males and 8 females) with average 5.75 months of duration and 29 healthy controls (19 males and 10 females) age 18 to 45 years old were recruited for clinical assessment and imaging scan. FreeSurfer was used to segment the hippocampus bilaterally, and hippocampal volumes were extracted for group and gender comparisons. Cognitive function was measured using the CogState Battery Chinese language version (CSB-C). Results Analysis of covariance (ANCOVA) controlling for education showed a significant group by gender interaction for right hippocampal relative volume adjusted for total brain size (p=0.002). Female patients showed significantly less volume compared with female healthy controls; there was no significant difference in volume between male patients and male healthy controls. Within female patients, there were significant negative relationships between right hippocampal volume and average dose of MA use (p=0.001), as well as the total error scores on the Continuous Paired Association Learning Task (CPAL) in CSB-C (p=0.013). Conclusions There seems to be a gender difference in how MA affects hippocampal volume and cognitive function in abstinent MA users. Hippocampus might be an important treatment target for cognitive improvement and functional recovery in this patient population, especially in females. PMID:25920682

  1. Correlates of nonmedical use of stimulants and methamphetamine use in a national sample

    PubMed Central

    Chen, Lian-Yu; Strain, Eric C.; Alexandre, Pierre Kébreau; Alexander, G. Caleb; Mojtabai, Ramin; Martins, Silvia S.

    2014-01-01

    Background Despite chemical similarities, ADHD stimulants and methamphetamine have distinct use patterns in the community. This study compared the characteristics of nonmedical ADHD stimulants users and methamphetamine users in a household sample. Methods In data from the 2009–2011 National Survey on Drug Use and Health, adult and adolescent stimulant users were categorized into three mutually exclusive subgroups: nonmedical ADHD stimulant users only (STM users), methamphetamine users (METH users), and both nonmedical ADHD stimulant and methamphetamine users (STM/METH users). Multivariate logistic regression analyses identified the substance comorbidity, mental health, and deviant behavior characteristics associated with these three groups. Results Compared to adolescent STM users, STM/METH users were more likely to be female, younger and uninsured while METH users were more likely to be younger, in a minority group and from a higher-income family. Compared to adult STM users, METH and STM/METH users were more likely to be male, older, uninsured, no longer married, and to be from rural areas. Adolescent METH users were more likely than STM users to report illegal drug use while adult METH users were less likely to report prescription drug use than their STM user counterparts. Overall, adult and adolescent STM/METH users were more likely to report substance use, mental health problems and deviant behaviors compared to STM users. Conclusion The characteristics of STM users differ from METH and STM/METH users, and their associations with substance use and psychiatric comorbidities differ by age. Findings have implications for understanding the risks for stimulant use in different age subgroups. PMID:24583271

  2. Olfactory bulbectomy increases reinstatement of methamphetamine seeking after a forced abstinence in rats.

    PubMed

    Babinska, Zuzana; Ruda-Kucerova, Jana; Amchova, Petra; Merhautova, Jana; Dusek, Ladislav; Sulcova, Alexandra

    2016-01-15

    Drug addiction is commonly associated with depression and comorbid patients also suffer from higher cravings and increased relapse rate. To address this issue preclinically we combined the olfactory bulbectomy (OBX) model of depression and intravenous methamphetamine self-administration procedure in rats to assess differences in relapse-like behavior. Male Sprague-Dawley rats were divided randomly into two groups; in one group the bilateral olfactory bulbectomy (OBX) was performed while the other group was sham operated. After recovery, intracardiac catheter was implanted. Intravenous self-administration procedure was conducted in operant boxes using nose-poke operandi (Coulbourn Instruments, Inc., USA) under fixed ratio 1 schedule of reinforcement. Methamphetamine was available at dose 0.08 mg/kg/infusion. After stable methamphetamine intake was maintained, a period of forced abstinence was initiated and rats were kept in their home-cages for 14 days. Finally, one reinstatement session was conducted in operant boxes with no drug delivery. In the reinstatement session the mean of 138.4 active nose-pokes was performed by the OBX group, while the sham group displayed 41 responses, i.e. 140 % and 48 % of basal nose-poking during maintenance phase in OBX and sham operated group respectively. OBX group also showed significantly more passive nose-pokes indicating hyperactive behavioral traits in bulbectomized rats. However, the % of active operandum preference was equal in both groups. Olfactory bulbectomy model significantly increased reinstatement of methamphetamine seeking behavior. This paradigm can be used to evaluate potential drugs that are able to suppress the drug-seeking behavior. PMID:26431766

  3. School-Related Factors Affecting High School Seniors' Methamphetamine Use

    ERIC Educational Resources Information Center

    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…

  4. A Qualitative Exploration of Trajectories among Suburban Users of Methamphetamine

    ERIC Educational Resources Information Center

    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…

  5. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    PubMed Central

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  6. Prevention of Methamphetamine Abuse: Can Existing Evidence Inform Community Prevention?

    ERIC Educational Resources Information Center

    Birckmayer, Johanna; Fisher, Deborah A.; Holder, Harold D.; Yacoubian, George S.

    2008-01-01

    Little research exists on effective strategies to prevent methamphetamine production, distribution, sales, use, and harm. As a result, prevention practitioners (especially at the local level) have little guidance in selecting potentially effective strategies. This article presents a general causal model of methamphetamine use and harms that…

  7. Why Is Parkinsonism Not a Feature of Human Methamphetamine Users?

    ERIC Educational Resources Information Center

    Moszczynska, Anna; Fitzmaurice, Paul; Ang, Lee; Kalasinsky, Kathryn S.; Schmunk, Gregory A.; Peretti, Frank J.; Aiken, Sally S.; Wickham, Dennis J.; Kish, Stephen J.

    2004-01-01

    For more than 50 years, methamphetamine has been a widely used stimulant drug taken to maintain wakefulness and performance and, in high doses, to cause intense euphoria. Animal studies show that methamphetamine can cause short-term and even persistent depletion of brain levels of the neurotransmitter dopamine. However, the clinical features of…

  8. Methamphetamine Abuse and Manufacture: The Child Welfare Response

    ERIC Educational Resources Information Center

    Hohman, Melinda; Oliver, Rhonda; Wright, Wendy

    2004-01-01

    Methamphetamine abuse is on the rise, particularly by women of child-bearing age. This article describes the history and effects of methamphetamine use. The authors examine the ways exposure to the manufacture of this drug affects clients and social workers in the course of their work. Because children are frequently found at the scene of a…

  9. The Patients in Recovery (PIR) Perspective: Teaching Physicians about Methamphetamine

    ERIC Educational Resources Information Center

    Walley, Alexander Y.; Phillips, Karran A.; Gordon, Adam J.

    2008-01-01

    Methamphetamine dependence is an emerging epidemic confronting physicians. In an effort to improve understanding of its impact, the authors presented an educational workshop at a national meeting for general internists featuring small group discussions with patients in recovery (PIR) from methamphetamine dependence. Participants rated the workshop…

  10. Psychiatric comorbidity of methamphetamine dependence in a forensic sample.

    PubMed

    Kalechstein, A D; Newton, T F; Longshore, D; Anglin, M D; van Gorp, W G; Gawin, F H

    2000-01-01

    The objective of this study was to examine the association between psychiatric symptoms and methamphetamine dependence. A four-hour survey was administered to 1,580 arrestees sampled from the 14 most populous counties in California. The survey included items assessing demographic profile, history of substance dependence, and psychiatric symptomatology. In the 12 months prior to the assessment, methamphetamine-dependent individuals were more likely to report depressive symptoms and suicidal ideation than individuals denying methamphetamine dependence, even after controlling for demographic profile and dependence on other drugs. Methamphetamine-dependent individuals also were more likely to report a need for psychiatric assistance at the time of the interview. These findings suggest that methamphetamine-dependent individuals are at greater risk to experience particular psychiatric symptoms. Further study to determine the etiology of these symptoms is warranted. PMID:11083165

  11. Study on the THz spectrum of methamphetamine

    NASA Astrophysics Data System (ADS)

    Ning, Li; Shen, Jingling; Jinhai, Sun; Laishun, Liang; Xu, Xiaoyu; Lu, Meihong; Yan, Jia

    2005-09-01

    The spectral absorption features of methamphetamine (MA), one of the most widely consumed illicit drugs in the world, are studied experimentally by Terahertz (THz) time-domain spectroscopy (THz-TDS), and the characteristic absorption spectra are obtained in the range of 0.2 to 2.6 THz. The vibrational frequencies are calculated using the density functional theory (DFT). Theoretical results show significant agreement with experimental results, and identification of vibrational modes are given. The calculated results further confirm that the characteristic frequencies come from the collective vibrational modes. The results suggest that use of the THz-TDS technique can be an effective way to inspect for illicit drugs.

  12. Methamphetamine Dependence and Neuropsychological Functioning: Evaluating Change During Early Abstinence*

    PubMed Central

    Simon, Sara L.; Dean, Andy C.; Cordova, Xochitl; Monterosso, John R.; London, Edythe D.

    2010-01-01

    Objective: The purpose of this work was to assess neuropsychological functioning of individuals in early abstinence from methamphetamine dependence and to test for cognitive change over the first month of abstinence. Method: Methamphetamine-dependent subjects in very early abstinence from methamphetamine (4–9 days; n = 27) were compared with healthy comparison subjects (n = 28) on a test battery that evaluated five cognitive domains (attention/processing speed, learning/memory, working memory, timed executive functioning, and untimed executive functioning). A subsample of the methamphetamine-dependent subjects (n = 18), who maintained abstinence for 1 month, as well as a subsample of the comparison subjects (n = 21), were retested. Results: At the first assessment, the methamphetamine-dependent subjects showed significantly worse performance than the comparison group on a test of processing speed; they also performed 0.31 SDs worse than the control group on a global battery composite score (p < .05). After a month of abstinence, methamphetamine-dependent subjects demonstrated slightly more cognitive improvement than healthy control subjects on the entire cognitive battery, but this difference did not approach statistical significance (p = .33). Conclusions: Our findings suggest that methamphetamine-dependent subjects do not show considerable cognitive gains in the first month of abstinence. A greater length of abstinence may be needed for cognitive improvement. PMID:20409426

  13. Differential regional effects of methamphetamine on dopamine transport.

    PubMed

    Chu, Pei-Wen; Seferian, Kristi S; Birdsall, Elisabeth; Truong, Jannine G; Riordan, James A; Metcalf, Cameron S; Hanson, Glen R; Fleckenstein, Annette E

    2008-08-20

    Multiple high-dose methamphetamine administrations cause long-lasting (>1 week) deficits in striatal dopaminergic neuronal function. This stimulant likewise causes rapid (within 1 h) and persistent (at least 48 h) decreases in activities of striatal: 1) dopamine transporters, as assessed in synaptosomes; and 2) vesicular monoamine transporter -2 (VMAT-2), as assessed in a non-membrane-associated (referred to herein as cytoplasmic) vesicular subcellular fraction. Importantly, not all brain areas are vulnerable to methamphetamine-induced long-lasting deficits. Similarly, the present study indicates that methamphetamine exerts differential acute effects on monoaminergic transporters according to brain region. In particular, results revealed that in the nucleus accumbens, methamphetamine rapidly, but reversibly (within 24 h), decreased plasmalemmal dopamine transporter function, without effect on plasmalemmal dopamine transporter immunoreactivity. Methamphetamine also rapidly and reversibly (within 48 h) decreased cytoplasmic VMAT-2 function in this region, with relatively little effect on cytoplasmic VMAT-2 immunoreactivity. In contrast, methamphetamine did not alter either dopamine transporter or VMAT-2 activity in the hypothalamus. Noteworthy, the nucleus accumbens and hypothalamus did not display the persistent long-lasting striatal dopamine depletions caused by the stimulant. Taken together, these data suggest that deficits in plasmalemmal and vesicular monoamine transporter activity lasting greater than 24-48 h may be linked to the long-lasting dopaminergic deficits caused by methamphetamine and appear to be region specific. PMID:18599036

  14. ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse.

    PubMed

    Barak, Larry S; Bai, Yushi; Peterson, Sean; Evron, Tama; Urs, Nikhil M; Peddibhotla, Satyamaheshwar; Hedrick, Michael P; Hershberger, Paul; Maloney, Patrick R; Chung, Thomas D Y; Rodriguiz, Ramona M; Wetsel, William C; Thomas, James B; Hanson, Glen R; Pinkerton, Anthony B; Caron, Marc G

    2016-07-15

    Pharmacological treatment for methamphetamine addiction will provide important societal benefits. Neurotensin receptor NTR1 and dopamine receptor distributions coincide in brain areas regulating methamphetamine-associated reward, and neurotensin peptides produce behaviors opposing psychostimulants. Therefore, undesirable methamphetamine-associated activities should be treatable with druggable NTR1 agonists, but no such FDA-approved therapeutics exist. We address this limitation with proof-of-concept data for ML314, a small-molecule, brain penetrant, β-arrestin biased, NTR1 agonist. ML314 attenuates amphetamine-like hyperlocomotion in dopamine transporter knockout mice, and in C57BL/6J mice it attenuates methamphetamine-induced hyperlocomotion, potentiates the psychostimulant inhibitory effects of a ghrelin antagonist, and reduces methamphetamine-associated conditioned place preference. In rats, ML314 blocks methamphetamine self-administration. ML314 acts as an allosteric enhancer of endogenous neurotensin, unmasking stoichiometric numbers of hidden NTR1 binding sites in transfected-cell membranes or mouse striatal membranes, while additionally supporting NTR1 endocytosis in cells in the absence of NT peptide. These results indicate ML314 is a viable, preclinical lead for methamphetamine abuse treatment and support an allosteric model of G protein-coupled receptor signaling. PMID:27119457

  15. Desorption of a methamphetamine surrogate from wallboard under remediation conditions

    NASA Astrophysics Data System (ADS)

    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.

  16. Glutamatergic Neurometabolites during Early Abstinence from Chronic Methamphetamine Abuse

    PubMed Central

    Tobias, Marc C.; Hudkins, Matthew; London, Edythe D.

    2015-01-01

    Background: 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. Methods: 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. Results: In the methamphetamine group, small but significant (5–15%, P<.05) decrements (vs control) in glutamate+glutamine were observed in posterior cingulate, precuneus, and right inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (P<.05) with years of methamphetamine abuse. The Beck Depression Inventory score was negatively correlated (P<.005) with glutamate+glutamine in right inferior frontal cortex. Conclusions: 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. PMID:25522400

  17. Decreased frontal lobe phosphocreatine levels in methamphetamine users

    PubMed Central

    Sung, Young-Hoon; Yurgelun-Todd, Deborah A.; Shi, Xian-Feng; Kondo, Douglas G.; Lundberg, Kelly J.; McGlade, Erin C.; Hellem, Tracy L.; Huber, Rebekah S.; Fiedler, Kristen K.; Harrell, Renee E.; Nickerson, Bethany R.; Kim, Seong-Eun; Jeong, Eun-Kee; Renshaw, Perry F.

    2012-01-01

    BACKGROUND Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with highenergy phosphate metabolism have not been investigated in METH users. Phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and β-nucleoside triphosphate (β-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=0.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=0.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0 gram) of METH use than males (1.4±1.7 gram), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=0.02). CONCLUSIONS The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels. PMID:23084413

  18. Induction of testicular damage by daily methamphetamine administration in rats.

    PubMed

    Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

    2014-02-28

    Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes. PMID:24621335

  19. Neurologic Manifestations of Chronic Methamphetamine Abuse

    PubMed Central

    Rusyniak, Daniel E.

    2013-01-01

    COMMENTARY ON METHAMPHETAMINE ABUSE FOR PSYCHIATRIC PRACTICE Every decade seems to have its own unique drug problem. The 1970s had hallucinogens, the 1980s had crack cocaine, the 1990s had designer drugs, the 2000s had methamphetamine (Meth), and in the 2010s we are dealing with the scourge of prescription drug abuse. While each of these drug epidemics has distinctive problems and history, the one with perhaps the greatest impact on the practice of Psychiatry is Meth. By increasing the extracellular concentrations of dopamine while slowly damaging the dopaminergic neurotransmission, Meth is a powerfully addictive drug whose chronic use preferentially causes psychiatric complications. Chronic Meth users have deficits in memory and executive functioning as well as higher rates of anxiety, depression, and most notably psychosis. It is because of addiction and chronic psychosis from Meth abuse that the Meth user is most likely to come to the attention of the practicing Psychiatrist/Psychologist. Understanding the chronic neurologic manifestations of Meth abuse will better arm practitioners with the diagnostic and therapeutic tools needed to make the Meth epidemic one of historical interest only. PMID:23688691

  20. Injury associated with methamphetamine use: A review of the literature

    PubMed Central

    Sheridan, Janie; Bennett, Sara; Coggan, Carolyn; Wheeler, Amanda; McMillan, Karen

    2006-01-01

    This paper reviews the literature exploring issues around methamphetamine and injury. There was a paucity of peer reviewed quantitative research and a lack of large scale epidemiological studies. Further sources described cases and others described injury risk as part of an overall review of methamphetamine misuse. Thus, a number of limitations and potential biases exist within the literature. The main areas where associations were noted or extrapolated with methamphetamine use and injury were around driving and violence. Other associations with injury related to methamphetamine manufacture. There was also circumstantial evidence for third party injury (that is injury to those not specifically involved in drug use or drug manufacture); however, the available data are inadequate to confirm these associations/risks. PMID:16571134

  1. METHAMPHETAMINE TOXICITY AND MESSENGERS OF DEATH

    PubMed Central

    Krasnova, Irina N.; Cadet, Jean Lud

    2009-01-01

    Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. In the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity. PMID:19328213

  2. Melatonin Attenuates Methamphetamine-Induced Neurotoxicity.

    PubMed

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2016-01-01

    Methamphetamine (METH), an illegal psycho-stimulant, is widely known as a recreational drug. In addition to its addictive effect, METH induces neurotoxicity via multiple mechanisms. The major contributors to METH-induced neurotoxicity are reactive oxygen species, which lead to cell death through apoptotic pathway and disturbances in mitochondria, the generation of neuroinflammation, and autophagy. Melatonin, a neurohormone secreted by the pineal gland, is a potent antioxidant compound that plays a beneficial role by protecting against the oxidative stress caused by METH. Melatonin also plays a role in maintaining mitochondrial homeostasis. Nanomolar concentrations of melatonin have been shown to protect against the inflammation caused by METH and to prevent the decrease in neurogenesis caused by METH in progenitor cells obtained from adult rat hippocampal tissue. The intent of this review is to describe the underlying mechanisms involving melatonin that protect against the neurodegeneration caused by METH. PMID:25248807

  3. Impact of methamphetamine on infection and immunity

    PubMed Central

    Salamanca, Sergio A.; Sorrentino, Edra E.; Nosanchuk, Joshua D.; Martinez, Luis R.

    2015-01-01

    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. PMID:25628526

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

    PubMed Central

    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

  5. Methamphetamine and the Changing Face of Child Welfare: Practice Principles for Child Welfare Workers

    ERIC Educational Resources Information Center

    Connell-Carrick, Kelli

    2007-01-01

    Methamphetamine use and production is changing child welfare practice. Methamphetamine is a significant public health threat (National Institute of Justice, 1999) reaching epidemic proportions (Anglin, Burke, Perrochet, Stamper, & Dawud-Nouris, 2000). The manufacturing of methamphetamine is a serious problem for the child welfare system, yet child…

  6. The Rise in Methamphetamine Use among American Indians in Los Angeles County

    ERIC Educational Resources Information Center

    Spear, Suzanne; Crevecoeur, Desiree A.; Rawson, Richard A.; Clark, Rose

    2007-01-01

    A preliminary review of substance abuse treatment admission data from 2001-2005 was conducted to explore the use of methamphetamine among American Indians in treatment programs funded by Los Angeles County. Comparisons were made between primary methamphetamine users and users whose primary drug was a substance other than methamphetamine. In that…

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

    ERIC Educational Resources Information Center

    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.…

  8. Characterization of the guinea pig animal model and subsequent comparison of the behavioral effects of selective dopaminergic drugs and methamphetamine

    PubMed Central

    Lee, Kiera-Nicole; Pellom, Samuel T.; Oliver, Ericka; Chirwa, Sanika

    2014-01-01

    Though not commonly used in behavior tests guinea pigs may offer subtle behavior repertoires that better mimic human activity and warrant study. To test this, 31 Hartley guinea pigs (male, 200–250 g) were evaluated in PhenoTyper cages using the video-tracking EthoVision XT 7.0 software. Results showed that guinea pigs spent more time in the hidden zone (small box in corner of cage) than the food/water zone, or arena zone. Guinea pigs exhibited thigmotaxis (a wall following strategy) and were active throughout the light and dark phases. Eating and drinking occurred throughout the light and dark phases. An injection of 0.25 mg/kg SCH23390, the dopamine D1 receptors (D1R) antagonist, produced significant decreases in time spent in the hidden zone. There were insignificant changes in time spent in the hidden zone for guinea pigs treated with 7.5 mg SKF38393 (D1R agonist), 1.0 mg/kg sulpiride (D2R antagonist), and 1.0 or 10.0 mg/kg methamphetamine. Locomotor activity profiles were unchanged after injections of saline, SKF38393, SCH23390 and sulpiride. By contrast, a single injection or repeated administration for 7 days of low-dose methamphetamine induced transient hyperactivity but this declined to baseline levels over the 22-hour observation period. Guinea pigs treated with high-dose methamphetamine displayed sustained hyperactivity and travelled significantly greater distances over the circadian cycle. Subsequent 7-day treatment with high-dose methamphetamine induced motor sensitization and significant increases in total distances moved relative to single drug injections or saline controls. These results highlight the versatility and unique features of the guinea pig for studying brain-behavior interactions. PMID:24436154

  9. Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms.

    PubMed

    Bagnall, John; Malia, Louis; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2013-10-01

    Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds. PMID:23886544

  10. Failure of surgical treatment in methamphetamine body-stuffers.

    PubMed

    Bahrami-Motlagh, Hooman; Hassanian-Moghaddam, Hossein; Behnam, Behdad; Arab-Ahmadi, Mehran

    2015-05-01

    Body stuffing is defined as ingestion of unpackaged or packaged illicit drugs in a quick process. The drugs have usually been wrapped loosely in cellophane, plastic bags, paper, or aluminum foil. Methamphetamine toxicity is a dangerous state that occurs during methamphetamine leakage from the ingested packages in the gastrointestinal tract. This is usually occurring with cocaine and heroin, but methamphetamine body stuffing may less commonly happen, as well. Accordingly, management of methamphetamine body-stuffers is an important subject that has remained a controversy in clinical and legal aspects. We have reported two body-stuffer cases who underwent exploratory laparotomy. Although surgery was done, it was not useful to exit packs and even led to severe methamphetamine toxicity. These cases show that surgical treatment may be ineffective and even harmful in body-stuffers. On the other hand, this report suggests that pre and post-operation abdominal CT-scan is necessary for evaluating surgical treatment in patients who are still symptomatic. PMID:25882154

  11. The blood-brain barrier and methamphetamine: open sesame?

    PubMed Central

    Turowski, Patric; Kenny, Bridget-Ann

    2015-01-01

    The chemical and electrical microenvironment of neurons within the central nervous system is protected and segregated from the circulation by the vascular blood–brain barrier. This barrier operates on the level of endothelial cells and includes regulatory crosstalk with neighboring pericytes, astrocytes, and neurons. Within this neurovascular unit, the endothelial cells form a formidable, highly regulated barrier through the presence of inter-endothelial tight junctions, the absence of fenestrations, and the almost complete absence of fluid-phase transcytosis. The potent psychostimulant drug methamphetamine transiently opens the vascular blood–brain barrier through either or both the modulation of inter-endothelial junctions and the induction of fluid-phase transcytosis. Direct action of methamphetamine on the vascular endothelium induces acute opening of the blood-brain barrier. In addition, striatal effects of methamphetamine and resultant neuroinflammatory signaling can indirectly lead to chronic dysfunction of the blood-brain barrier. Breakdown of the blood-brain barrier may exacerbate the neuronal damage that occurs during methamphetamine abuse. However, this process also constitutes a rare example of agonist-induced breakdown of the blood-brain barrier and the adjunctive use of methamphetamine may present an opportunity to enhance delivery of chemotherapeutic agents to the underlying neural tissue. PMID:25999807

  12. The Clinical Pharmacology of Intranasal l-Methamphetamine

    PubMed Central

    Mendelson, John E; McGlothlin, Dana; Harris, Debra S; Foster, Elyse; Everhart, Tom; Jacob, Peyton; Jones, Reese T

    2008-01-01

    Background We studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant. Methods 12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 μg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured. Results Plasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 ± 56.1, 124.7 ± 106.6, and 268.1 ± 220.5 μg for ascending exposures (mean 4.2 ± 3.3 μg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen. Conclusion Inhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant. PMID:18644153

  13. Methamphetamine abuse and “meth mouth” in Europe

    PubMed Central

    Boyd, Geraldine-A.; Mancinelli, Luca; Pagano, Stefano; Eramo, Stefano

    2015-01-01

    With easy chemical synthesis from its precursor, methamphetamine (MA) is now widespread in many countries. The abuse of methamphetamine is associated with several negative effects on health, because MA is a neurotoxin and a dangerous central nervous system stimulant. It changes levels of neurotransmitters in the brain, releasing dopamine and inhibiting nor epinephrine uptake which increases sympathetic nervous system activity and can lead to cardiac arrhythmia, hypertension and tachypnea. The consequences of MA abuse are clearly manifested in oral diseases (like “meth mouth”) which is characterised by extensive caries, teeth grinding with ensuing dental wear and trismus. The present review was designed to fill the gap in knowledge about methamphetamine abuse in the European Union (EU) and to illustrate the main clinical effects of prolonged use. After describing the pharmacology and systemic effects of methamphetamine and concentrating on its effects on the mouth, the present review compares the epidemiology and incidence of abuse in the world, particularly the USA and the EU. Key words:Methamphetamine, “Meth mouth”, drug abuse, oral health. PMID:25662544

  14. Duration Effects in Contingency Management Treatment of Methamphetamine Disorders

    PubMed Central

    Roll, John M.; Chudzynski, Joy; Cameron, Jennifer M.; Howell, Donelle N.; McPherson, Sterling

    2013-01-01

    The primary aim of this study was to determine whether different durations of contingency management (CM) in conjunction with psychosocial treatment produced different rates of abstinence among methamphetamine dependent individuals. Participants were randomized to one of four 16-week treatment conditions: standard psychosocial treatment or psychosocial treatment plus one of three durations of CM (one-month, two-month, or four-month). A total of 118 participants were randomized to the four treatment conditions. There were significant differences across treatment conditions for number of consecutive days of methamphetamine abstinence (p < 0.05). These differences were in the hypothesized direction, as participants were more likely to remain abstinent through the 16-week trial as CM duration increased. A significant effect of treatment condition (p < 0.05) and time (p < 0.05) on abstinence over time was also found. Longer durations of CM were more effective for maintaining methamphetamine abstinence. PMID:23708468

  15. The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

    PubMed Central

    Ferrucci, Michela; Giorgi, Filippo S; Bartalucci, Alessia; Busceti, Carla L; Fornai, Francesco

    2013-01-01

    The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters. PMID:23814540

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

    PubMed

    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. PMID:10711406

  17. The Methamphetamine Problem in the United States

    PubMed Central

    Gonzales, Rachel; Mooney, Larissa; Rawson, Richard

    2015-01-01

    Significant public health problems associated with methamphetamine (MA) production and use in the United States have emerged over the past 25 years. Although the popular press (Newsweek, Aug 8, 2008), has called MA “America’s Most Dangerous Drug” there has been considerable controversy about the size of the problem. Epidemiological indicators have given a mixed picture. National surveys of the adult U.S. population and school-based populations have consistently been used to support the position that MA use is a relatively minor concern (NSDUH, 2006; Johnston & O’Malley, 2007). However, many other data sources, including law-enforcement groups, welfare agencies, substance abuse treatment program admission data, data on criminal justice populations, and state/county executives indicate that MA is a very significant public health problem for many communities throughout much of the country (NDIC, 2007b; NACO, 2005, 2006; NIDA CEWG, 2007). In this article, we describe (1) the historical underpinnings of the MA problem, (2) trends in the epidemiological nature of the MA problem, (3) key subgroups at risk for MA problems, (4) the health and social factors associated with MA use, (5) interventions available for addressing the MA problem, and (5) lessons learned related to the MA problem. PMID:20070191

  18. Violence perpetrated by women who use methamphetamine

    PubMed Central

    HAMILTON, ALISON B.; GOEDERS, NICHOLAS E.

    2015-01-01

    Methamphetamine (meth) is widely recognized as being associated with violence and aggression. This association is found among women and men, with rates of meth-related violence among women possibly being equal to or even exceeding rates among men. This study examined female-perpetrated violence from the phenomenological point of view of 30 women (aged 18–45 years; mean age of 28.5 years) in residential treatment for meth dependence. Of the 30 participants, 80% (n = 24) reported experiencing violence in their lifetimes: 67% (n = 20) had violence perpetrated against them, and 57% (n = 17) had perpetrated violence. Most participants described perpetrating violence when they were ‘coming down’ off of meth (i.e. withdrawing). Five women (29%) attributed their violent behaviors to meth and said they would not have been violent had they not been using meth. In contrast, 10 women (59%) described pre-existing ‘anger issues’ that were ‘enhanced’ by meth. This article describes the timing of meth-related violence, bi-directional violence, men’s responses to female-perpetrated violence, aggression in the context of sexual activities, and violence perpetrated against non-partners. A biopsychosocial theoretical framework is useful to interpret the complex explanations that women provide for their perpetration of violence under the influence of chronic meth use. PMID:26045288

  19. Role for Rab10 in Methamphetamine-Induced Behavior

    PubMed Central

    Vanderwerf, Scott M.; Buck, David C.; Wilmarth, Phillip A.; Sears, Leila M.; David, Larry L.; Morton, David B.; Neve, Kim A.

    2015-01-01

    Lipid rafts are specialized, cholesterol-rich membrane compartments that help to organize transmembrane signaling by restricting or promoting interactions with subsets of the cellular proteome. The hypothesis driving this study was that identifying proteins whose relative abundance in rafts is altered by the abused psychostimulant methamphetamine would contribute to fully describing the pathways involved in acute and chronic effects of the drug. Using a detergent-free method for preparing rafts from rat brain striatal membranes, we identified density gradient fractions enriched in the raft protein flotillin but deficient in calnexin and the transferrin receptor, markers of non-raft membranes. Dopamine D1- and D2-like receptor binding activity was highly enriched in the raft fractions, but pretreating rats with methamphetamine (2 mg/kg) once or repeatedly for 11 days did not alter the distribution of the receptors. LC-MS analysis of the protein composition of raft fractions from rats treated once with methamphetamine or saline identified methamphetamine-induced changes in the relative abundance of 23 raft proteins, including the monomeric GTP-binding protein Rab10, whose abundance in rafts was decreased 2.1-fold by acute methamphetamine treatment. Decreased raft localization was associated with a selective decrease in the abundance of Rab10 in a membrane fraction that includes synaptic vesicles and endosomes. Inhibiting Rab10 activity by pan-neuronal expression of a dominant-negative Rab10 mutant in Drosophila melanogaster decreased methamphetamine-induced activity and mortality and decreased caffeine-stimulated activity but not mortality, whereas inhibiting Rab10 activity selectively in cholinergic neurons had no effect. These results suggest that activation and redistribution of Rab10 is critical for some of the behavioral effects of psychostimulants. PMID:26291453

  20. Association Study of Serine Racemase Gene with Methamphetamine Psychosis

    PubMed Central

    Yokobayashi, E; Ujike, H; Kotaka, T; Okahisa, Y; Takaki, M; Kodama, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Kuroda, S

    2011-01-01

    Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our recent genetic studies provided evidence that genetic variants of glutamate-related genes such as DTNBP1, GLYT1, and G72, which are involved in glutamate release and regulation of co-agonists for NMDA receptors, conferred susceptibility to methamphetamine psychosis. Serine racemase converts l-serine to d-serine, which is an endogenous co-agonist for NMDA receptors. Three single nucleotide polymorphisms (SNPs) in the promoter region of the serine racemase gene (SRR), rs224770, rs3760229, and rs408067, were proven to affect the transcription activity of SRR. Therefore, we examined these SNPs in 225 patients with methamphetamine psychosis and 291 age- and sex-matched controls. There was no significant association between methamphetamine psychosis and any SNP examined or between the disorder and haplotypes comprising the three SNPs. However, rs408067 was significantly associated with the prognosis for methamphetamine psychosis and multi-substance abuse status. The patients with C-positive genotypes (CC or CG) of rs408067 showed better prognosis of psychosis after therapy and less abuse of multiple substances than the patients with GG genotypes. Because the C allele of rs408067 reduces the expression of SRR, a lower d-serine level or reduced NMDA receptor activation may affect the prognosis of methamphetamine psychosis and multiple substance abuse. Our sample size is, however, not large enough to eliminate the possibility of a type I error, our findings must be confirmed by replicate studies with larger samples. PMID:21886585

  1. Neural Correlates of Affect Processing and Aggression in Methamphetamine Dependence

    PubMed Central

    Payer, Doris E.; Lieberman, Matthew D.; London, Edythe D.

    2012-01-01

    Context Methamphetamine abuse is associated with high rates of aggression, but few studies have addressed the contributing neurobiological factors. Objective To quantify aggression, investigate function of the amygdala and prefrontal cortex, and assess relationships between brain function and behavior in methamphetamine-dependent individuals. Design In a case-control study, aggression and brain activation were compared between methamphetamine-dependent and control participants. Setting Participants were recruited from the general community to an academic research center. Participants Thirty-nine methamphetamine-dependent volunteers (16 women) who were abstinent for 7 to 10 days and 37 drug-free control volunteers (18 women) participated in the study; subsets completed self-report and behavioral measures. Functional magnetic resonance imaging (fMRI) was performed on 25 methamphetamine-dependent and 23 control participants. Main outcome measures We measured self-reported and perpetrated aggression, and self-reported alexithymia. Brain activation was assessed using fMRI during visual processing of facial affect (affect matching), and symbolic processing (affect labeling), the latter representing an incidental form of emotion regulation. Results Methamphetamine-dependent participants self-reported more aggression and alexithymia than control participants and escalated perpetrated aggression more following provocation. Alexithymia scores correlated with measures of aggression. During affect matching, fMRI showed no differences between groups in amygdala activation, but found lower activation in methamphetamine-dependent than control participants in bilateral ventral inferior frontal gyrus. During affect labeling, participants recruited dorsal inferior frontal gyrus and exhibited decreased amygdala activity, consistent with successful emotion regulation; there was no group difference in this effect. The magnitude of decrease in amygdala activity during affect labeling

  2. Association of the Neuronal Cell Adhesion Molecule (NrCAM) Gene Variants with Personality Traits and Addictive Symptoms in Methamphetamine Use Disorder

    PubMed Central

    Yoo, Byung Kuk; Shim, Joo Cheol; Kim, Choongrak; Chung, Young In; Park, Je Min; Kim, Sung Gon; Kim, Ji Hoon; Lee, Young Min; Moon, Eun Soo; Kwon, Do Hoon

    2012-01-01

    Objective 1) To investigate the relationship between NrCAM polymorphisms and methamphetamine abuse in an ethnically homogenous Korean population. 2) To further support our findings by investigating the association among NrCAM gene variants, certain personality traits, and addictive symptoms of methamphetamine abusers. Methods Thirty-seven male methamphetamine abusers (age=43.3±7.8) and30 non-users (16 men, 14 women; age=59.8±10.4) were recruited. Ten single nucleotide polymorphisms (SNPs) in the NrCAM gene were assayed to compare genotype distributions between the 2 groups. Personality characteristics were measured using the Temperament and Character Inventory (TCI) and the NEO Personality Inventory, Revised (NEO PI-R). Addictive symptoms were assessed using the Diagnostic Interview for Genetic Studies (DIGS) and reviews of the subject's medical records. Results Among the 10 SNPs in the NrCAM gene, the frequency of the TA genotype at rs1990162 was significantly lower in methamphetamine abusers compared to non-users (p=0.042). In the 3 NrCAM gene SNPs (rs381318, rs2072546, and rs6954366), the distribution of genotypes and alleles were significantly associated with some traits in the TCI and NEO PI-R. Genotypes and alleles at 5 gene SNPs (rs2142325, rs381318, rs1269621, rs1269634, and rs1990162) were associated with certain addictive symptom dimensions in the patients. Conclusion These findings support the idea that NrCAM is associated with genetic susceptibility of methamphetamine abuse and is also associated with certain personality characteristics that may increase disturbed addictive behavior. PMID:23251206

  3. Estimating the intake of abused methamphetamines using experimenter-administered deuterium labeled R-methamphetamine: selection of the R-methamphetamine dose.

    PubMed

    Li, Linghui; Lopez, Juan Carlos; Galloway, Gantt P; Baggott, Matthew J; Everhart, Tom; Mendelson, John

    2010-08-01

    All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, the quantity of illicit drug ingested is related to the severity of addiction. Unfortunately, there are no objective methods to estimate intake for most addictive drugs. Using experimenter-administered doses of deuterium-labeled R-methamphetamine (R-[-]-MA-d3), we have developed a method to estimate the amount of abused methamphetamine intake in addicts enrolled in clinical trials. This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of single oral doses of R-MA in healthy adults to select a dose of R-MA-d3 to be used as a biomarker for estimation the amount of methamphetamine abuse. This was a five-session randomized, double-blind, placebo-controlled, balanced crossover study in eight subjects. Oral R-(-)-MA was dosed at 0 mg, 1 mg, 2.5 mg, 5 mg, or 10 mg; bioavailability was estimated by slow intravenous dosing (30 minutes) of 2.5 mg R-(-)-MA-d3 given with the 2.5 mg R-(-)-MA oral dose condition. Pharmacokinetic and pharmacodynamic measures were obtained. No serious adverse events occurred during the study and all doses of R-MA were well tolerated. Linear pharmacokinetics was observed within our oral dose range of 1 to 10 mg. Complete bioavailability and pharmacologic inactivity were found for all oral doses. These characteristics indicate the advantage of using a small oral R-(-)-MA-d3 dose as a biomarker to estimate exposure to abused methamphetamine. Based on these results, 5 mg R-(-)-MA-d3 has been selected as the biomarker dose in future studies. Preliminary findings from our study indicate that experimenter-administered oral R-(-)-MA-d3 may allow estimation of abused methamphetamine intake and exposure. Knowledge of the quantity of methamphetamine intake may allow better estimation of disease severity and treatment efficacy. Experience gained from this study also can be applied to the management of other drug dependence problems such as

  4. Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

    PubMed Central

    Kuhn, Donald M.; Angoa-Pérez, Mariana; Thomas, David M.

    2016-01-01

    Methamphetamine (Meth) is a neurotoxic drug of abuse that damages neurons and nerve endings throughout the central nervous system. Emerging studies of human Meth addicts using both postmortem analyses of brain tissue and noninvasive imaging studies of intact brains have confirmed that Meth causes persistent structural abnormalities. Animal and human studies have also defined a number of significant functional problems and comorbid psychiatric disorders associated with long-term Meth abuse. This review summarizes the salient features of Meth-induced neurotoxicity with a focus on the dopamine (DA) neuronal system. DA nerve endings in the caudate-putamen (CPu) are damaged by Meth in a highly delimited manner. Even within the CPu, damage is remarkably heterogeneous, with ventral and lateral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared the damage that accompanies binge Meth intoxication, but relatively subtle changes in the disposition of DA in its nerve endings can lead to dramatic increases in Meth-induced toxicity in the CPu and overcome the normal resistance of the NAc to damage. In contrast to the CPu, where DA neuronal deficiencies are persistent, alterations in the NAc show a partial recovery. Animal models have been indispensable in studies of the causes and consequences of Meth neurotoxicity and in the development of new therapies. This research has shown that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of Meth to include brain structures not normally targeted for damage. The resistance of the NAc to Meth-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of Meth neurotoxicity by alterations in DA homeostasis is significant in light of the numerous important roles played by this brain structure. PMID:23382149

  5. Brain site- and transmitter-dependent actions of methamphetamine, morphine and antipsychotics.

    PubMed

    Mori, Tomohisa; Iwase, Yoshiyuki; Murata, Asami; Iwata, Noriyuki; Suzuki, Tsutomu

    2016-06-01

    While several methamphetamine- and morphine-induced psychotic states are ordinarily treated by antipsychotics, the therapeutic mechanisms of antipsychotic drugs have yet been elucidated. The present study was designed to investigate the mechanisms how antipsychotic drugs suppress the behavioral changes induced by psychoactive drugs in mice. Low to medium doses of methamphetamine produced hyperlocomotion, whereas high dose of methamphetamine induced hypolocomotion. Hyperlocomotion induced by methamphetamine was potently suppressed by clozapine and 5-HT2 receptor antagonists, but not by the intra-accumbens injection of haloperidol. On the other hand, microinjection of haloperidol into the ventrolateral striatum increased locomotor activity with high dose of methamphetamine. In contrast, morphine-induced hyperlocomotion was suppressed by systemic as well as intra-accumbens injection of haloperidol, whereas relatively resistant to clozapine, compared to its effects in the case of methamphetamine. It has been widely believed that methamphetamine-induced psychosis is an animal model of schizophrenia, which is mediated by activation of accumbal dopamine receptors. Our findings suggest that methamphetamine differentially regulate monoaminergic systems (e.g., dopaminergic vs. 5-HTnergic), and accumbal dopamine receptors are not involved in methamphetamine-induced hyperlocomotion in mice. Thus, our findings may lead to a better understanding of the therapeutic mechanisms that underlie the effects of antipsychotic drugs and behavioral effects of methamphetamine and morphine. PMID:26992824

  6. The advent of a new pseudoephedrine product to combat methamphetamine abuse

    PubMed Central

    Leech, Ronald; Stark, Jeffrey G.

    2013-01-01

    Background: The personal and societal effects of methamphetamine abuse are well documented. The ease of accessibility to methamphetamine and the quality of the “high” it produces makes the drug highly desired by its abusers. Over time, many methamphetamine users will also become methamphetamine cooks, where pseudoephedrine in over-the-counter cold products is converted to methamphetamine through a simple, albeit extremely dangerous, process. New laws limiting access to these products have had limited success. No existing commercial pseudoephedrine products offer significant impediments to slow or limit the extraction and conversion of pseudoephedrine in clandestine methamphetamine laboratories. Objective and Methods: A new pseudoephedrine 30 mg tablet product using Impede technology (Nexafed®) to deter methamphetamine production has recently been introduced into the marketplace. Using methods designed to mimic clandestine laboratory processes, the ability of this product to disrupt extraction and conversion of pseudoephedrine to methamphetamine yet provide therapeutic effectiveness was evaluated. Results: Impede™ technology tablets limited the extraction and/or conversion of pseudoephedrine to methamphetamine when compared to a commercially marketed pseudoephedrine product (Sudafed®). Nexafed® tablets were also shown to be bioequivalent to the same control product, thus ensuring therapeutic equivalence. Conclusions: With the advent of new pseudoephedrine products in the marketplace with features to limit the extraction and conversion of pseudoephedrine to methamphetamine, new tools are now available to minimize the clandestine manufacture of the drug and potentially limit its social impact. PMID:23968171

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

    PubMed

    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. PMID:27055611

  8. The Central Amygdala Nucleus is Critical for Incubation of Methamphetamine Craving

    PubMed Central

    Li, Xuan; Zeric, Tamara; Kambhampati, Sarita; Bossert, Jennifer M; Shaham, Yavin

    2015-01-01

    Cue-induced methamphetamine seeking progressively increases after withdrawal but mechanisms underlying this ‘incubation of methamphetamine craving' are unknown. Here we studied the role of central amygdala (CeA), ventral medial prefrontal cortex (vmPFC), and orbitofrontal cortex (OFC), brain regions implicated in incubation of cocaine and heroin craving, in incubation of methamphetamine craving. We also assessed the role of basolateral amygdala (BLA) and dorsal medial prefrontal cortex (dmPFC). We trained rats to self-administer methamphetamine (10 days; 9 h/day, 0.1 mg/kg/infusion) and tested them for cue-induced methamphetamine seeking under extinction conditions during early (2 days) or late (4–5 weeks) withdrawal. We first confirmed that ‘incubation of methamphetamine craving' occurs under our experimental conditions. Next, we assessed the effect of reversible inactivation of CeA or BLA by GABAA+GABAB receptor agonists (muscimol+baclofen, 0.03+0.3 nmol) on cue-induced methamphetamine seeking during early and late withdrawal. We also assessed the effect of muscimol+baclofen reversible inactivation of vmPFC, dmPFC, and OFC on ‘incubated' cue-induced methamphetamine seeking during late withdrawal. Lever presses in the cue-induced methamphetamine extinction tests were higher during late withdrawal than during early withdrawal (incubation of methamphetamine craving). Muscimol+baclofen injections into CeA but not BLA decreased cue-induced methamphetamine seeking during late but not early withdrawal. Muscimol+baclofen injections into dmPFC, vmPFC, or OFC during late withdrawal had no effect on incubated cue-induced methamphetamine seeking. Together with previous studies, results indicate that the CeA has a critical role in incubation of both drug and non-drug reward craving and demonstrate an unexpected dissociation in mechanisms of incubation of methamphetamine vs cocaine craving. PMID:25475163

  9. Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans*

    PubMed Central

    Dean, Andy C.; Sevak, Rajkumar J.; Monterosso, John R.; Hellemann, Gerhard; Sugar, Catherine A.; London, Edythe D.

    2011-01-01

    Objective: Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafinil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafinil have been reported in several populations, little is known about the effects of modafinil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals. Method: Seventeen healthy subjects and 24 methamphetamine-dependent subjects participated in this randomized, double-blind, placebo-controlled, crossover study. Effects of modafinil (200 mg, single oral dose) were assessed on participants’ performance on tests of inhibitory control, working memory, and processing speed/attention. Results: Across subjects, modafinil improved performance on a test of sustained attention, with no significant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. Conclusions: Although modafinil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use. These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently. PMID:22051208

  10. Triangular congenital cataract morphology associated with prenatal methamphetamine exposure.

    PubMed

    Clarke, Michael E; Schloff, Susan; Bothun, Erick D

    2009-08-01

    Bilateral congenital cataracts are often characterized by morphology, etiology, and related conditions. We report a case of unique congenital cataracts with triangular morphology and associated prenatal methamphetamine exposure. Although this association is likely coincidental, the cataract's morphology in light of the specific timing of prenatal drug use deserves reporting. PMID:19464935

  11. An Emerging Problem: Methamphetamine Abuse among Treatment Seeking Youth

    ERIC Educational Resources Information Center

    Gonzales, Rachel; Ang, Alfonso; McCann, Michael J.; Rawson, Richard A.

    2008-01-01

    This study examined correlates of methamphetamine (MA) and marijuana (MJ) use and treatment response among treatment-involved youth (N = 4,430) in Los Angeles County, California treated between 2000 and 2005. Of the sample, 912 (21%) were primary MA and 3,518 (79%) were primary MJ users. Correlates of increased MA use included being female, White,…

  12. Open-label pilot study of modafinil for methamphetamine dependence.

    PubMed

    McGaugh, Janette; Mancino, Michael J; Feldman, Zachary; Chopra, Mohit P; Gentry, W Brooks; Cargile, Christopher; Oliveto, Alison

    2009-10-01

    Methamphetamine has become a major public health issue globally, particularly in the United States. Despite this, no effective pharmacotherapy for methamphetamine abuse has been developed to date. This 6-week, open-label pilot clinical trial examined the safety and tolerability of modafinil up to 400 mg/d in 8 methamphetamine-dependent individuals. Subjects were inducted onto modafinil at 400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks. Participants received weekly blister packs and underwent weekly individual cognitive behavioral therapy. Adjunctive contingency management procedures were used to enhance retention. Vital signs and supervised urine samples were obtained thrice weekly, and self-reported drug use and Hamilton anxiety and depression ratings were completed once weekly. Eight subjects (50% female, 100% white, aged 35-52 years) were enrolled. Four completed the 6-week study, 3 completed a portion, and 1 withdrew consent before completing intake. Results showed that systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t = 1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time. Scores on the modafinil side effects checklist (t = -2.63, P = 0.01), Hamilton anxiety scale (t = -2.50, P = 0.018), and Hamilton depression scale (t = -3.25, P = 0.003) all decreased over time. The proportion of urine positive for amphetamines did not change over time (t = -0.52, P = 0.61), whereas self-reported methamphetamine use did (t = -2.86, P < 0.005). These results suggest that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent individuals. PMID:19745650

  13. Genetic factors involved in risk for methamphetamine intake and sensitization

    PubMed Central

    Belknap, John K.; McWeeney, Shannon; Reed, Cheryl; Burkhart-Kasch, Sue; McKinnon, Carrie S.; Li, Na; Baba, Harue; Scibelli, Angela C.; Hitzemann, Robert; Phillips, Tamara J.

    2013-01-01

    Lines of mice were created by selective breeding for the purpose of identifying genetic mechanisms that influence magnitude of the selected trait and to explore genetic correlations for additional traits thought to be influenced by shared mechanisms. DNA samples from high and low methamphetamine drinking (MADR) and high and low methamphetamine sensitization lines were used for quantitative trait locus (QTL) mapping. Significant additive genetic correlations between the two traits indicated common genetic influence, and a QTL on chromosome X was detected for both traits, suggesting one source of this commonality. For MADR mice, a QTL on chromosome 10 accounted for more than 50% of the genetic variance in that trait. Microarray gene expression analyses were performed for 3 brain regions for methamphetamine-naïve MADR line mice: nucleus accumbens, prefrontal cortex and ventral midbrain. Many of the genes that were differentially expressed between the high and low MADR lines were shared in common across the 3 brain regions. A gene network highly enriched in transcription factor genes was identified as being relevant to genetically-determined differences in methamphetamine intake. When the mu opioid receptor gene (Oprm1), located on chromosome 10 in the QTL region, was added to this top ranked transcription factor network, it became a hub in the network. These data are consistent with previously published findings of opioid response and intake differences between the MADR lines and suggest that Oprm1 or a gene that impacts activity of the opioid system, plays a role in genetically–determined differences in methamphetamine intake. PMID:24217691

  14. Decontamination of clothing and building materials associated with the clandestine production of methamphetamine.

    PubMed

    Serrano, Kate A; Martyny, John W; Kofford, Shalece; Contreras, John R; Van Dyke, Mike V

    2012-01-01

    This study was designed to determine how easily methamphetamine can be removed from clothing and building materials, utilizing different cleaning materials and methods. The study also addressed the penetration of methamphetamine into drywall and the ability of paints to encapsulate the methamphetamine on drywall. Clothing and building materials were contaminated in a stainless steel chamber by aerosolizing methamphetamine in a beaker heater. The amount of methamphetamine surface contamination was determined by sampling a grid pattern on the material prior to attempting to clean the materials. After cleaning, the materials were again sampled, and the degree of decontamination noted. We found that household clothing and response gear worn by first responders was easily decontaminated using a household detergent in a household washing machine. A single wash removed over 95% of the methamphetamine from these materials. The study also indicated that methamphetamine-contaminated, smooth non-porous surfaces can be easily cleaned to below detectable levels using only mild cleaners. More porous surfaces such as plywood and drywall were unlikely to be decontaminated to below regulatory levels even with three washes using a mild cleaner. This may be due to methamphetamine penetration into the paint on these surfaces. Evaluation of methamphetamine contamination on drywall indicated that approximately 40% of the methamphetamine was removed using a wipe, while another 60% remained in the paint layer. Stronger cleaners such as those with active ingredients including sodium hypochlorite or quaternary ammonia and commercial decontamination agents were more effective than mild detergent-based cleaners and may reduce methamphetamine contamination to below regulatory levels. Results from the encapsulation studies indicate that sprayed on oil-based paint will encapsulate methamphetamine on drywall and plywood surfaces up to 4.5 months, while latex paints were less effective. PMID

  15. Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum

    PubMed Central

    Goitia, Belen; Garcia-Rill, Edgar; Krasnova, Irina N.; Cadet, Jean Lud; Urbano, Francisco J.; Bisagno, Veronica

    2012-01-01

    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. PMID:23056363

  16. HIV testing behaviors and attitudes among community recruited methamphetamine users in a South African township

    PubMed Central

    Meade, Christina S.; Towe, Sheri L.; Watt, Melissa H.; Hobkirk, Andrea; Skinner, Donald; Myers, Bronwyn; Kimani, Stephen M.; Pieterse, Desiree

    2015-01-01

    Background Methamphetamine users in South Africa are at high risk for HIV infection and transmission, but little is known about HIV testing in this population. Methods We examined HIV testing behaviors and attitudes in 362 methamphetamine users recruited using chain referral sampling from one peri-urban community. Results Many (44%) had not been HIV tested in the past year. HIV testing was associated with positive testing attitudes, less AIDS stigma, and greater methamphetamine stigma. Among participants who reported HIV infection (8%), less than half were linked to care. Conclusions Findings highlight the need to identify barriers to HIV service uptake for methamphetamine users. PMID:24858393

  17. Methamphetamine-induced toxicity: an updated review on issues related to hyperthermia

    PubMed Central

    Matsumoto, Rae R.; Seminerio, Michael J.; Turner, Ryan C.; Robson, Matthew J.; Nguyen, Linda; Miller, Diane B.; O’Callaghan, James P.

    2015-01-01

    Reports of methamphetamine-related emergency room visits suggest that elevated body temperature is a universal presenting symptom, with lethal overdoses generally associated with extreme hyperthermia. This review summarizes the available information on methamphetamine toxicity as it pertains to elevations in body temperature. First, a brief overview of thermoregulatory mechanisms is presented. Next, central and peripheral targets that have been considered for potential involvement in methamphetamine hyperthermia are discussed. Finally, future areas of investigation are proposed, as further studies are needed to provide greater insight into the mechanisms that mediate the alterations in body temperature elicited by methamphetamine. PMID:24836729

  18. Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

    SciTech Connect

    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

    2008-03-01

    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.

  19. Sex Differences in Activation of the Hypothalamic-Pituitary-Adrenal Axis by Methamphetamine

    PubMed Central

    Zuloaga, Damian G; Johnson, Lance A; Agam, Maayan; Raber, Jacob

    2014-01-01

    Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activation is associated with changes in addiction-related behaviors. In this study we tested whether sex differences in the acute effects of methamphetamine (MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c-Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C-Fos was elevated in both sexes following MA in HPA axis-associated regions, including the hypothalamic paraventricular nucleus (PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c-Fos and c-Fos/glucocorticoid receptor (GR) dual-labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c-fos/vasopressin dual-labeled cells in the PVN as well as the number and percentage of c-Fos/GR dual-labeled cells in the PVN and central amygdala, although no sex differences in dual-labeling were found in these regions. Thus, sex differences in MA-induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain. PMID:24400874

  20. Metabolism of [14C]methamphetamine in man, the guinea pig and the rat

    PubMed Central

    Caldwell, J.; Dring, L. G.; Williams, R. T.

    1972-01-01

    1. The metabolites of (±)-2-methylamino-1-phenyl[1-14C]propane ([14C]methamphetamine) in urine were examined in man, rat and guinea pig. 2. In two male human subjects receiving the drug orally (20mg per person) about 90% of the 14C was excreted in the urine in 4 days. The urine of the first day was examined for metabolites, and the main metabolites were the unchanged drug (22% of the dose) and 4-hydroxymethamphetamine (15%). Minor metabolites were hippuric acid, norephedrine, 4-hydroxyamphetamine, 4-hydroxynorephedrine and an acid-labile precursor of benzyl methyl ketone. 3. In the rat some 82% of the dose of 14C (45mg/kg) was excreted in the urine and 2–3% in the faeces in 3–4 days. In 2 days the main metabolites in the urine were 4-hydroxymethamphetamine (31% of dose), 4-hydroxynorephedrine (16%) and unchanged drug (11%). Minor metabolites were amphetamine, 4-hydroxyamphetamine and benzoic acid. 4. The guinea pig was injected intraperitoneally with the drug at two doses, 10 and 45mg/kg. In both cases nearly 90% of the 14C was excreted, mainly in the urine after the lower dose, but in the urine (69%) and faeces (18%) after the higher dose. The main metabolites in the guinea pig were benzoic acid and its conjugates. Minor metabolites were unchanged drug, amphetamine, norephedrine, an acid-labile precursor of benzyl methyl ketone and an unknown weakly acidic metabolite. The output of norephedrine was dose-dependent, being about 19% on the higher dose and about 1% on the lower dose. 5. Marked species differences in the metabolism of methamphetamine were observed. The main reaction in the rat was aromatic hydroxylation, in the guinea pig demethylation and deamination, whereas in man much of the drug, possibly one-half, was excreted unchanged. PMID:4646771

  1. Reinstatement of Methamphetamine Conditioned Place Preference in Nicotine-Sensitized Rats

    PubMed Central

    Berry, Jennifer N.; Neugebauer, Nichole M.; Bardo, Michael T.

    2012-01-01

    The current experiments examined the effects of repeated nicotine prior to acquisition, extinction, and reinstatement of methamphetamine-induced conditioned place preference (CPP). Methamphetamine-induced (METH; 0.25, 0.5, or 1 mg/kg, s.c.) CPP was established using separate groups of adult male Sprague-Dawley rats with an unbiased conditioning procedure. Following extinction of METH CPP, drug-primed reinstatement (0, 0.25, 0.5 or 1 mg/kg, s.c.) of METH CPP was assessed in order to determine whether METH-induced reinstatement depends on the METH dose used to induce CPP. In a second experiment, separate groups of rats received nicotine (NIC; 0 or 0.2 mg/kg, s.c.) for 7 days prior to undergoing METH (0 or 0.5 mg/kg, s.c.) conditioning, extinction, and drug-primed reinstatement. Results indicate that METH-primed reinstatement varied as a function of dose such that priming with the conditioning dose did not reinstate CPP, but reinstatement was observed following priming doses of METH that were either lower or higher than the conditioning dose. Prior NIC exposure had no effect on METH CPP, extinction, or reinstatement. Interestingly, at a METH dose (0.5 mg/kg) that did not induce reinstatement alone, acute NIC (0.2 mg/kg) in combination with METH induced reinstatement, suggesting that NIC produced a leftward shift in the dose-response effect of METH to reinstate CPP. These studies indicate that prior NIC exposure may not be necessary for enhancement of the rewarding effects of METH, in contrast to previous self-administration reports. PMID:22884606

  2. Adaptation of a Couple-Based HIV Intervention for Methamphetamine-Involved African American Men who have Sex with Men

    PubMed Central

    Wu, Elwin; El-Bassel, Nabila; Donald McVinney, L.; Fontaine, Yves-Michel; Hess, Leona

    2010-01-01

    In the U.S., incidence of HIV infection among men who have sex with men (MSM) has steadily increased since the 1990s. This points to a need for innovation to address both emerging trends as well as longer-standing disparities in HIV risk and transmission among MSM, such as the elevated rates of HIV/STIs among African American MSM and methamphetamine users. While couple-based sexual risk reduction interventions are a promising avenue to reduce HIV/STI transmission, prior research has been almost exclusively with heterosexual couples. We sought to adapt an existing, evidence-based intervention—originally developed and tested with heterosexual couples—for a new target population consisting of African American MSM in a longer-term same-sex relationship where at least one partner uses methamphetamine. The adaptation process primarily drew from data obtained from a series of focus groups with 8 couples from the target population. Attention is given to the methods used to overcome challenges faced in this adaptation process: limited time, a lead investigator who is phenotypically different from the target population, a dearth of descriptive information on the experiences and worldviews among the target population, and a concomitant lack of topical experts. We also describe a visualization tool used to ensure that the adaptation process promotes and maintains adherence to the theory that guides the intervention and behavior change. The process culminated with an intervention adapted for the new target population as well as preliminary indications that a couple-based sexual-risk reduction intervention for African American, methamphetamine-involved male couples is feasible and attractive. PMID:20657720

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

    PubMed

    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

  4. Effects of methamphetamine and scopolamine on variability of response location.

    PubMed Central

    Moerschbaecher, J M; Thompson, D M; Thomas, J R

    1979-01-01

    Methamphetamine and scopolamine were studied in monkeys responding under a multiple fixed-ratio fixed-interval schedule of reinforcement. A response on any one of six levers could satisfy the schedule requirements. Variability of response location was evaluated in terms of switches, where a switch was defined as a response on one lever followed by a response on a different lever. Under baseline conditions the fixed-ratio schedule generated a high rate of responding and a low level of variability, while the fixed-interval schedule generated a low rate of responding and a high level of variability. Both methamphetamine (0.1 to 0.5 mg/kg) and scopolamine (2.4 to 240 microgram/kg) decreased overall response rate and increased variability of response location in each component of the multiple schedule with increasing doses of drug. At lower doses both drugs were found to decrease rate without affecting response variability. PMID:115956

  5. Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine

    PubMed Central

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

    2013-01-01

    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 amongst drug abusers. PMID:23892199

  6. Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine.

    PubMed

    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. PMID:23892199

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

    PubMed Central

    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

    2013-01-01

    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 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. PMID:21190217

  8. Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines.

    PubMed

    Dayrit, Fabian M; Dumlao, Morphy C

    2004-08-11

    Methamphetamine hydrochloride is one of the most widely used illicit drugs in the Philippines. In this study, we describe the application of cluster analysis of trace impurities in the profiling of the seized methamphetamine drug samples. Thirty milligrams of a homogenized drug sample were dissolved in 1 mL of pH 10.5 buffer solution and extracted with ethyl acetate containing three internal standards. The trace impurities were identified using gas chromatography-mass spectrometry (GC-MS) and quantified by gas chromatography with a flame ionization detector (GC-FID). Following previously reported methodologies, 30 impurity peaks were selected from the GC-FID chromatograms. The peak areas and retention times were referenced to the internal standards. The peak areas of the selected peaks were then grouped for cluster analysis. In order to check for consistency of clustering, two further cluster analyses were performed using 40 and 50 impurity peaks. Changes in clustering were observed in going from 30 to 40 impurity peaks, while analyses using 40 and 50 impurity peaks gave similar results. Thus, for the seized drug samples used in this study, cluster analysis using at least 40 impurity peaks showed better consistency of clustering as compared to analysis using 30 peaks only. Ten of the impurity peaks were identified, of which four were identified for the first time in methamphetamine drug samples. These are p-bromotoluene, N-benzyl amphetamine, N-ethyl amphetamine, and N-ethyl methamphetamine. The presence of phenyl-2-propanone (P2P), N,N-dimethyl amphetamine, and N-formyl amphetamine is indicative that these casework samples were synthesized using the Leuckart method. PMID:15240018

  9. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity

    PubMed Central

    Yazdani, Neema; Parker, Clarissa C.; Shen, Ying; Reed, Eric R.; Guido, Michael A.; Kole, Loren A.; Kirkpatrick, Stacey L.; Lim, Jackie E.; Sokoloff, Greta; Cheng, Riyan; Johnson, W. Evan; Palmer, Abraham A.; Bryant, Camron D.

    2015-01-01

    Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512–50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J)—a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes—heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1) and RUN and FYVE domain-containing 1 (Rufy1). Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2), a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10−15). Transcription activator-like effector nucleases (TALENs)-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for prevention

  10. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

    PubMed

    Yazdani, Neema; Parker, Clarissa C; Shen, Ying; Reed, Eric R; Guido, Michael A; Kole, Loren A; Kirkpatrick, Stacey L; Lim, Jackie E; Sokoloff, Greta; Cheng, Riyan; Johnson, W Evan; Palmer, Abraham A; Bryant, Camron D

    2015-12-01

    Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J)-a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1) and RUN and FYVE domain-containing 1 (Rufy1). Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2), a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10-15). Transcription activator-like effector nucleases (TALENs)-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for prevention and

  11. Partial MHC/Neuroantigen Peptide Constructs: A Potential Neuroimmune-Based Treatment for Methamphetamine Addiction

    PubMed Central

    Loftis, Jennifer M.; Wilhelm, Clare J.; Vandenbark, Arthur A.; Huckans, Marilyn

    2013-01-01

    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-Ab/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. PMID:23460798

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

    SciTech Connect

    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.

  13. The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth

    ERIC Educational Resources Information Center

    Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Grotta, Sheri Della; Liu, Jing; Lester, Barry M.

    2007-01-01

    Objective: Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development,…

  14. Impurities in Illicit Drug Preparations: Amphetamine and Methamphetamine.

    PubMed

    Verweij, A M

    1989-06-01

    In this review, attention is paid to chromatographic and mass spectral properties of already identified impurities found to be present in frequently abused drug preparations of illegal origin of amphetamine and methamphetamine. The most commonly employed methods of synthesis of drugs of this type are briefly described. Special emphasis is given to the Leuckart route, found to be the preferred method, in the illicit production of amphetamine. Furthermore, some isolation and preconcentration methods for the contaminants are discussed. The importance of identifying impurities present in amphetamine or methamphetamine cannot be overestimated. These impurities originate mostly from the improper purification in the end stage of the different syntheses used in the clandestine manufacture of the substances; it is possible to differentiate between the several kinds of illegal drug preparations, synthesized by various methods, by means of so-called "route specific" impurities. Finally, a survey is given of the impurities already known to be present in amphetamine and methamphetamine, together with their mass spectral and some chromatographic properties. PMID:26266521

  15. Methamphetamine exposure and chronic illness in police officers

    PubMed Central

    Ross, Gerald H; Sternquist, Marie C

    2012-01-01

    Background: The medical literature reports health hazards for law enforcement personnel from repeated exposure to methamphetamine and related chemical compounds. Most effects appear transitory, but some Utah police officers with employment-related methamphetamine exposures developed chronic symptoms, some leading to disability. This report is of an uncontrolled retrospective medical chart evaluation of symptomatic officers treated with a sauna detoxification protocol designed to reduce the chronic symptoms and improve the quality of life. Methods: Sixty-nine officers consecutively entering the Utah Meth Cops Project were assessed before and after a treatment program involving gradual exercise, comprehensive nutritional support and physical sauna therapy. Evaluations included pre- and post-treatment scores of the Research and Development Corporation (RAND) 36-item Short Form Health Survey (SF-36) in comparison with RAND population norms, pre- and post-treatment symptom score intensities, neurotoxicity scores, Mini-Mental Status Examination, presenting symptom frequencies and a structured evaluation of treatment program safety. Results: Statistically significant health improvements were seen in the SF-36 evaluations, symptom scores and neurotoxicity scores. The detoxification protocol was well tolerated, with a 92.8% completion rate. Conclusions: This investigation strongly suggests that utilizing sauna and nutritional therapy may alleviate chronic symptoms appearing after chemical exposures associated with methamphetamine-related law enforcement activities. This report also has relevance to addressing the apparent ill effects of other complex chemical exposures. In view of the positive clinical outcomes in this group, broader investigation of this sauna-based treatment regimen appears warranted. PMID:22089658

  16. Methamphetamine use and malnutrition among street-involved youth

    PubMed Central

    2010-01-01

    We sought to explore the effect of crystal methamphetamine use on the risk of experiencing malnutrition among street-involved youth in Vancouver, Canada. Risk of malnutrition was defined as being hungry but not having enough money to buy food. Socio-demographic and drug use factors associated with risk of malnutrition were investigated using univariate and multivariate analysis among a prospective cohort of street-involved youth known as the At-Risk Youth Study (ARYS). Between September 2005 and December 2006, 509 street-involved youth were enrolled in ARYS, among whom 21% reported being at risk of malnutrition as defined above in the previous six months. In multivariate analysis, only non-injection crystal methamphetamine was significantly associated with being at risk of malnutrition among this cohort (Adjusted Odds Ratio [AOR] = 1.60, 95% Confidence Interval [CI]: 1.03 - 2.48, p = 0.036). Interventions seeking to address food insecurity among street youth may benefit from considering drug use patterns since methamphetamine use predicted higher risk in this setting. PMID:20210992

  17. Symptoms experienced by law enforcement personnel during methamphetamine lab investigations.

    PubMed

    Witter, Roxana Z; Martyny, John W; Mueller, Kathryn; Gottschall, Bibi; Newman, Lee S

    2007-12-01

    This study was conducted to determine if law enforcement personnel experience symptoms associated with methamphetamine lab investigation and to assess those factors that may result in more symptoms. A total of 258 standardized, self-administered surveys were distributed to law enforcement personnel attending national/regional training classes, between June 2004-February 2005. Ninety-three percent of the surveys were returned and used to determine symptoms experienced while investigating clandestine methamphetamine labs, as well as the job duties of the respondent and the personal protective equipment used. More than 70% of respondents reported headaches, central nervous system symptoms, respiratory symptoms, sore throat, and other symptoms. Unadjusted and adjusted risk of symptoms was higher for those who investigated more than 30 labs. Other significant risk factors included time spent in the lab, phase of investigation, presence of active chemical processes, and coexistent disease. Respirator use was not independently associated with the likelihood of reporting symptoms. It was concluded that methamphetamine lab investigation is positively associated with symptom reporting in a high percentage of law enforcement personnel involved in these tasks. For most individuals, the reported symptoms were transitory and diminished in a short time, but some individuals reported needing to seek medical attention with symptoms that persisted. PMID:17943587

  18. Methamphetamine Use Is Independently Associated with Recent Risky Sexual Behaviors and Adolescent Pregnancy

    ERIC Educational Resources Information Center

    Zapata, Lauren B.; Hillis, Susan D.; Marchbanks; Polly A.; Curtis, Kathryn M.; Lowry, Richard

    2008-01-01

    Background: Lifetime methamphetamine use among adolescents is estimated to be between 5% and 10%. Youth substance use in general is known to be associated with risky sexual behaviors, but the effect of methamphetamine use on recent risky sexual behaviors and adolescent pregnancy has received little attention. The purpose of this analysis was to…

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

    ERIC Educational Resources Information Center

    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.…

  20. Demand for Substance Abuse Treatment Related to Use of Crystal Methamphetamine in Ontario: An Observational Study

    ERIC Educational Resources Information Center

    Brands, Bruna; Corea, Larry; Strike, Carol; Singh, Veeran-Anne S.; Behrooz, Renee C.; Rush, Brian

    2012-01-01

    Concerns about methamphetamine/crystal methamphetamine (MA) have featured prominently in the Canadian media and on addiction treatment agency agendas. We examined MA admissions at addiction treatment agencies to determine if a service gap existed. In 2006, all addiction treatment agencies (n = 124) in Ontario, Canada were invited to complete an…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  3. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and...

  4. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and...

  5. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and...

  6. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers... 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...

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

    ERIC Educational Resources Information Center

    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…

  8. Illegal Methamphetamine Drug Laboratories: A New Challenge for Environmental Health Professionals.

    ERIC Educational Resources Information Center

    Skeers, Vicki M.

    1992-01-01

    Reports on clandestine drug laboratories for manufacturing methamphetamine; the formation of an interagency steering committee to address the problem; and the role Environmental Health professionals need to play as the problem becomes more prevalent across the United States. Provides background information on methamphetamine characteristics and…

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

    ERIC Educational Resources Information Center

    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…

  10. Case Series: Mental Health Needs and Perspectives of Rural Children Reared by Parents Who Abuse Methamphetamine

    ERIC Educational Resources Information Center

    Ostler, Teresa; Haight, Wendy; Black, James; Choi, Ga-Young; Kingery, Linda; Sheridan, Kathryn

    2007-01-01

    Objective: This case-based, mixed-methods study was undertaken to understand the perspectives and mental health needs of rural children exposed to parental methamphetamine abuse. Method: Participants were 23 children involved with a state child protective agency because of parental methamphetamine abuse. A semistructured interview provided…

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

    ERIC Educational Resources Information Center

    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…

  12. Methamphetamine Use, Self-Reported Violent Crime, and Recidivism Among Offenders in California Who Abuse Substances

    ERIC Educational Resources Information Center

    Cartier, Jerome; Farabee, David; Prendergast, Michael L.

    2006-01-01

    This study uses data from 641 state prison parolees in California to examine the associations between methamphetamine use and three measures of criminal behavior: (a) self-reported violent criminal behavior, (b) return to prison for a violent offense, and (c) return to prison for any reason during the first 12 months of parole. Methamphetamine use…

  13. 75 FR 13702 - Implementation of the Methamphetamine Production Prevention Act of 2008

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... Chemical Products'' (71 FR 56008; corrected at 71 FR 60609, October 13, 2006). That rule incorporated the... Enforcement Administration 21 CFR Part 1314 RIN 1117-AB25 Implementation of the Methamphetamine Production... Rulemaking. SUMMARY: In October 2008, the President signed the Methamphetamine Production Prevention Act...

  14. National Case-Control Study of Homicide Offending and Methamphetamine Use

    ERIC Educational Resources Information Center

    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…

  15. Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence

    PubMed Central

    Zorick, Todd; Sevak, Rajkumar J; Miotto, Karen; Shoptaw, Steven; Swanson, Aimee-Noelle; Clement, Clayton; De La Garza, Richard; Newton, Thomas F; London, Edythe D

    2010-01-01

    Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo-controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at α4b2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over one week to reach 1 mg twice daily, and then was co-administered with 30 mg methamphetamine, delivered in 10 intravenous (iv) infusions of 3 mg each. Varenicline was found to be safe in combination with iv methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence.

  16. Differences between patients with schizophrenia with and without co-occurring methamphetamine use disorders in a Taiwanese public psychiatric hospital.

    PubMed

    Lin, Ching-Hua; Huang, Yu-Hui; Wu, Hung-Chi; Chen, Cheng-Chung

    2014-11-01

    This study aimed to examine the factors related to and the outcomes of schizophrenic patients with co-occurring methamphetamine use disorders (MUDs). All schizophrenic patients discharged from a psychiatric hospital between January 1, 2006, and December 31, 2006, were monitored. This study compared the important demographic and clinical variables between patients with co-occurring MUDs and those without, and postdischarge measured time to rehospitalization during a 1-year period. Seven hundred fifty-six patients were included in this study. Of these patients, 88 (11.6%) reported the use of methamphetamine. Univariate analyses indicated that male sex, low educational level, discharge against medical advice, missed first appointment after discharge, co-occurring other illicit substance use disorder, age (younger), diazepam equivalents prescribed at discharge (higher), number of previous admissions within the past 5 years (higher), and length of hospital stay (longer) were predictive of patients with co-occurring MUDs. There were also significant differences in time to rehospitalization between these two groups during the follow-up periods. Many factors can be identified in schizophrenic patients with co-occurring MUDs. Furthermore, schizophrenic patients with co-occurring MUDs were more likely to be rehospitalized. Future studies in many different mental health systems are needed before these findings can be generalized. PMID:25268153

  17. Evaluation of Attention Bias in Morphine and Methamphetamine Abusers towards Emotional Scenes during Early Abstinence: An Eye-Tracking Study

    PubMed Central

    Soleimannejad, Maryam; Tehrani-Doost, Mehdi; Khorrami, Anahita; Joghataei, Mohammad Taghi; Pishyareh, Ebrahim

    2015-01-01

    Introduction: We hypothesized that inappropriate attention during the period of abstinence in individuals with substance use disorder can result in an inadequate perception of emotion and unsuitable reaction to emotional scenes. The main aim of this research was to evaluate the attentional bias towards emotional images in former substance abusers and compare it to healthy adults. Methods: Paired images of general scenes consisting of pleasant, unpleasant, and neutral images were presented to subjects for 3 s while their attentional bias and eye movements were measured by eye tracking. The participants were 72 male adults consisting of 23 healthy control, 24 morphine former abusers, and 25 methamphetamine former abusers. The former abusers were recruited from a private addiction quitting center and addiction rehabilitation campus. The healthy individuals were selected from general population. Number and duration of first fixation, duration of first gaze, and sustained attention towards emotional scenes were measured as the main variables and the data were analyzed using the repeated measures ANOVA. Results: A significant difference was observed between former morphine abusers and healthy control in terms of number and duration of first fixations and first gaze duration towards pleasant images. Discussion: Individuals with morphine use disorder have more problems with attending to emotional images compared to methamphetamine abusers and healthy people. PMID:26649160

  18. Relapse and Risk-taking among Iranian Methamphetamine Abusers Undergoing Matrix Treatment Model

    PubMed Central

    Taymoori, Parvaneh; Pashaei, Tahereh

    2016-01-01

    Background This study investigated the correlation between risk-taking and relapse among methamphetamine (MA) abusers undergoing the Matrix Model of treatment. Methods This cross-sectional study was conducted on male patients who were stimulant drug abusers undergoing the matrix treatment in the National Center for Addiction Research. A sampling was done using the availability method including 92 male patients. Demographic questionnaires and drug abuse related questionnaire were completed for each patient. Then, Bart’s balloon risk-taking test was administered to the patients. Findings Participants had a mean age ± standard deviation (SD) of 27.59 ± 6.60 years with an age range of 17-29 years. Unemployment, unmarried status, criminal offense, and also addiction family history increased the probability of relapse. In addition, a greater adjusted score of the risk-taking test increased the odds of relapse by more than 97%. The simultaneous abuse of opium and stimulants compared to the abuse of stimulants only, revealed no statistically significant differences for relapse. Patients with higher risk-taking behavior had a more probability of relapse. Conclusion This finding indirectly implies the usefulness of Bart’s risk-taking test in assessing risk-taking behavior in stimulant drug abusers. PMID:27274793

  19. Methamphetamine and the changing face of child welfare: practice principles for child welfare workers.

    PubMed

    Connell-Carrick, Kelli

    2007-01-01

    Methamphetamine use and production is changing child welfare practice. Methamphetamine is a significant public health threat (National Institute of Justice, 1999) reaching epidemic proportions (Anglin, Burke, Perrochet, Stamper, & Dawud-Nouris, 2000). The manufacturing of methamphetamine is a serious problem for the child welfare system, yet child welfare has not addressed the needs of children living in homes where methamphetamine is manufactured (U.S. Department of Justice, 2002; DOJ, 2003; Altshuler, 2005). This article presents key issues for child welfare workers related to the use, production, and effects of methamphetamine on children and families, and identifies practice principles for child welfare workers in order to ensure safety for victims, parents, and workers themselves. PMID:17722684

  20. Double-blind placebo-controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

    PubMed Central

    Ling, Walter; Shoptaw, Steven; Hillhouse, Maureen; Bholat, Michelle A.; Charuvastra, Charles; Heinzerling, Keith; Chim, David; Annon, Jeffrey; Dowling, Patrick T.; Doraimani, Geetha

    2014-01-01

    Aims To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence. Design A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Setting Three substance abuse treatment clinics: two in-patient, one out-patient. Participants Treatment-seeking, methamphetamine-dependent adults (n = 120). Measurements Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. Findings No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. Conclusions The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving. PMID:22082089

  1. Hair analysis and self-report of methamphetamine use by methamphetamine dependent individuals.

    PubMed

    Han, Eunyoung; Paulus, Martin P; Wittmann, Marc; Chung, Heesun; Song, Joon Myong

    2011-03-01

    The questions of whether the dose of drug that is consumed corresponds to drug concentration levels in hair and how results of hair analyses can be interpreted are still debated. The aim of this study was to investigate (1) whether there is a correlation between doses of Methamphetamine (MA) use and MA concentration levels in hair and (2) whether results of hair analyses can be used to estimate dose, frequency, and patterns of MA use. In this study, segmental hair analysis was performed through consecutive 1cm as well as 1-4 cm (=3 cm) segmental hair lengths. MA dependent individuals (n=9) provided information on doses (0.25-4 g/day) of MA use as well as the frequency of MA use. The concentrations of MA and its metabolite amphetamine (AP) in hair were determined using gas chromatography/mass spectrometry (GC/MS). One-way analysis of variance (ANOVA) test was performed to evaluate whether MA and AP concentrations in consecutive 1cm length segmental hair were consistent with the history of MA use. The cumulative doses of MA use calculated from the daily dose and the frequency during 1-4 months were well correlated to the concentrations of MA and AP in 1-4 cm segmental hair length (correlation coefficient, r=0.87 for MA and r=0.77 for AP). The results from this study show the patterns and histories of MA use from MA dependent individuals and could assist in the interpretation of hair results in forensic toxicology as well as in rehabilitation and treatment programs. PMID:21296038

  2. Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

    PubMed Central

    Lile, Joshua A.; Stoops, William W.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

    2015-01-01

    Background Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABAA activity following chronic stimulant use, and that positive modulation of GABAA receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABAA modulators could be useful as pharmacotherapies for stimulant-use disorders. Methods This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1 mg/day). Results Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment. Conclusions The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABAA positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABAA positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment. PMID:21737214

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

    PubMed Central

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

    2016-01-01

    Background: 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. Methods: 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. Results: 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. Conclusions: 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. PMID:26945022

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

    PubMed Central

    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

  5. Association of methamphetamine use during sex with risky sexual behaviors and HIV infection among non-injection drug users.

    PubMed Central

    Molitor, F; Truax, S R; Ruiz, J D; Sun, R K

    1998-01-01

    Morbidity, mortality, and drug treatment data suggest that methamphetamine use is on the rise. Based on research findings of the sexual behaviors of methamphetamine-using injection drug users, we chose to examine the relationship between methamphetamine use during sex and risky sexual behaviors and human immunodeficiency virus (HIV) seropositivity among clients of publicly funded HIV testing sites in California who reported never injecting drugs. We found that among gay, bisexual, and heterosexual men and heterosexual women, users of methamphetamines reported more sexual partners than non-methamphetamine users. Among heterosexuals, a greater percentage of methamphetamine users than nonusers participated in anal intercourse. Methamphetamine use was independently related to decreased condom use during vaginal and anal intercourse, prostitution, and sex with known injection drug users. In addition, methamphetamine users were more likely to have had a sexually transmitted disease. When controlling for race or ethnicity; age; exposure to possibly infected blood or blood products; and the use of cocaine, alcohol, or marijuana during sex, methamphetamine-using bisexual men were more likely to test positive for HIV than those reporting no history of methamphetamine use. Our data suggest that noninjection methamphetamine use is related to increased, unprotected sexual activity and the risk of contracting sexually transmitted diseases, including HIV. PMID:9499742

  6. Aggregate versus day level association between methamphetamine use and HIV medication non-adherence among gay and bisexual men

    PubMed Central

    Parsons, Jeffrey T.; Kowalczyk, William; Botsko, Michael; Tomassilli, Julia; Golub, Sarit A.

    2013-01-01

    Methamphetamine use is associated with HIV infection, especially among gay and bisexual men. Methamphetamine use contributes to disease progression both directly, by increasing viral load and damaging the immune system, and indirectly, by decreasing medication adherence. Research examining the association of methamphetamine use and non-adherence has traditionally compared groups of users and nonusers on adherence, compared methamphetamine use between participants above or below some threshold level of adherence (e.g. >90% dose adherence), or examined aggregate relationships. Using Timeline Follow-back procedures, the present study examined aggregate, threshold, and day-level associations of methamphetamine use with non-adherence in 210 HIV-positive gay and bisexual methamphetamine-using men. Methamphetamine use was not associated with adherence behavior at the aggregate-level, but methamphetamine use on a given day was associated with 2.3 times the odds of non-adherence on that day. Threshold results were equivocal. These data suggest that the methamphetamine and non-adherence relationship is complicated: non-adherence is more likely to occur on days in which methamphetamine is used, but participants reported more non-adherence days in which methamphetamine was not used. This seeming paradox generates questions about the selection of analytical techniques and has important implications for behavioral interventions targeting substance use and adherence among HIV-positive individuals. PMID:23553345

  7. Nanoparticle based galectin-1 gene silencing, implications in methamphetamine regulation of HIV-1 infection in monocyte derived macrophages.

    PubMed

    Reynolds, Jessica L; Law, Wing Cheung; Mahajan, Supriya D; Aalinkeel, Ravikumar; Nair, Bindukumar; Sykes, Donald E; Yong, Ken-Tye; Hui, Rui; Prasad, Paras N; Schwartz, Stanley A

    2012-09-01

    Galectin-1, an adhesion molecule, is expressed in macrophages and implicated in human immunodeficiency virus (HIV-1) viral adsorption. In this study, we investigated the effects of methamphetamine on galectin-1 production in human monocyte derived macrophages (MDM) and the role of galectin-1 in methamphetamine potentiation of HIV-1 infection. Herein we show that levels of galectin-1 gene and protein expression are significantly increased by methamphetamine. Furthermore, concomitant incubation of MDM with galectin-1 and methamphetamine facilitates HIV-1 infection compared to galectin-1 alone or methamphetamine alone. We utilized a nanotechnology approach that uses gold nanorod (GNR)-galectin-1 siRNA complexes (nanoplexes) to inhibit gene expression for galectin-1. Nanoplexes significantly silenced gene expression for galectin-1 and reversed the effects of methamphetamine on galectin-1 gene expression. Moreover, the effects of methamphetamine on HIV-1 infection were attenuated in the presence of the nanoplex in MDM. PMID:22689223

  8. Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy.

    PubMed

    Cunha, F S; Domenice, S; Câmara, V L; Sircili, M H P; Gooren, L J G; Mendonça, B B; Costa, E M F

    2015-08-01

    Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-administration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens. PMID:25059808

  9. Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration

    PubMed Central

    Polettini, Aldo; Cone, Edward J.; Gorelick, David A.; Huestis, Marilyn A.

    2012-01-01

    Background Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Material and Methods Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within one week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng/mg). Results MAMP Tmax occurred from 1 to 2 weeks after both doses, with Cmax ranging from 0.6–3.5 ng/mg after the low and 1.2–5.3 ng/mg after the high MAMP doses. AMP Cmax in hair was 0.1–0.3 ng/mg and 0.2–0.5 ng/mg, respectively, for low and high doses. Highly dose–related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng/mg cutoff for at least two weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15±0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r2=0.90, p=0.00) and AMP (r2=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between Cmax and melanin. Conclusions This study demonstrated that despite large

  10. Parental Methamphetamine Use and Manufacture: Child and Familial Outcomes

    PubMed Central

    Messina, Nena; Jeter, Kira

    2012-01-01

    The children of methamphetamine (MA) users and manufacturers are at high risk of neglect and abuse and physical harm from exposure to the drug and the chemicals used to produce it. This study is the first to document the epidemiology of children removed from home-based MA labs and their familial outcomes. Analyses are predominantly descriptive for 99 cases of drug-endangered children recorded from 2001–2003 in Los Angeles County. Neglect was substantiated in 93% of the cases; 97% of the cases resulted in child protective services detainment. Eighty percent had a documented medical diagnosis, most often related to exposure to MA manufacture. PMID:22879822

  11. Methamphetamine and the hypothalamic-pituitary-adrenal axis

    PubMed Central

    Zuloaga, Damian G.; Jacobskind, Jason S.; Raber, Jacob

    2015-01-01

    Psychostimulants such as methamphetamine (MA) induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA) axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure) on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such as anxiety and depression. A better understanding of the mechanisms through which MA affects the HPA axis may lead to more effective treatment strategies for MA addiction. PMID:26074755

  12. Acute lead poisoning in two users of illicit methamphetamine

    SciTech Connect

    Allcott, J.V. III; Barnhart, R.A.; Mooney, L.A.

    1987-07-31

    Acute lead poisoning can present a difficult diagnostic dilemma, with symptoms that mimic those of hepatitis, nephritis, and encephalopathy. The authors report two cases in intravenous methamphetamine users who presented with abnormal liver function values, low hematocrit values, basophilic stippling of red blood cells, and elevated blood lead levels. Both patients excreted large amounts of lead in their urine after treatment with edetic acid, followed by resolution of their symptoms. Lead contamination was proved in one drug sample. Basophilic stippling of the red blood cells was the one key laboratory result that led to the definitive diagnosis in both cases.

  13. Oral fluid with three modes of collection and plasma methamphetamine and amphetamine enantiomer concentrations after controlled intranasal l-methamphetamine administration.

    PubMed

    Newmeyer, Matthew N; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A; Huestis, Marilyn A

    2015-10-01

    Methamphetamine is included in drug testing programmes due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks® VapoInhaler™ administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks® VapoInhaler™ doses according to manufacturer's recommendations. Specimens were collected before and up to 32 h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1 μg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5 μg/L after 6 doses with the Quantisal™ and Oral-Eze® devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50 μg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0 μg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks® VapoInhaler™ administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler™ intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results. PMID:25786659

  14. Predictors of Safer Sex Intentions and Protected Sex Among Heterosexual HIV-Negative Methamphetamine Users

    PubMed Central

    Mausbach, Brent T.; Semple, Shirley J.; Strathdee, Steffanie A; Patterson, Thomas L.

    2009-01-01

    The purpose of this study was to test a version of the Theory of Planned Behavior (TPB) for predicting safe sex behavior in a sample of 228 HIV-negative heterosexual methamphetamine users. We hypothesized that, in addition to TPB constructs, participants’ amount of methamphetamine use and desire to stop unsafe sex behaviors would predict intentions to engage in safer sex behaviors. In turn, we predicted that safer sex intentions would be positively correlated with participants’ percentage of protected sex. Hierarchical linear regression indicated that 48% of the total variance in safer sex intentions was predicted by our model, with less negative attitudes toward safer sex, greater normative beliefs, greater control beliefs, less methamphetamine use, less intent to have sex, and greater desire to stop unsafe sex emerging as significant predictors of greater safer sex intentions. Safer sex intentions were positively associated with future percent protected sex (p<.05). These findings suggest that, among heterosexual methamphetamine users, the TPB is an excellent model for predicting safer sex practices in this population, as are some additional factors (e.g., methamphetamine use). Effective interventions for increasing safer sex practices in methamphetamine user will likely include constructs from this model with augmentations to help reduce methamphetamine use. PMID:19085216

  15. Social and Behavioral Characteristics of HIV-positive MSM Who Trade Sex for Methamphetamine

    PubMed Central

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

    2012-01-01

    Background Previous research among drug-using men who have sex with men (MSM) indicates that trading sex for methamphetamine may be common. Objectives This study identified background characteristics, substance use variables, contextual factors, and sexual risk behaviors associated with trading sex for methamphetamine in a sample of HIV-positive MSM. Baseline data were gathered from 155 participants who were enrolled in a sexual risk-reduction intervention. Logistic regression was used to compare MSM who traded sex for methamphetamine with men who did not. Results Forty-three percent of the sample reported trading sex for methamphetamine in the past 2 months. Trading sex for methamphetamine was associated with being a binge user, homelessness, having an income of less than $20,000 per year, being less assertive at turning down drugs, engaging in more anal sex without a condom, and seeking out risky sex partners when high on methamphetamine. Conclusions and Scientific Significance These data suggest that the trading of sex for methamphetamine may be a primary source of new HIV infections within and outside of the MSM community, necessitating targeted interventions with this vulnerable subgroup. PMID:20955106

  16. Examining the role of methamphetamine in permanency: A competing risks analysis of reunification, guardianship, and adoption.

    PubMed

    Akin, Becci A; Brook, Jody; Lloyd, Margaret H

    2015-03-01

    Parental methamphetamine use has drawn significant attention in recent years. Despite prior research that shows that parental substance abuse is a risk factor for lengthy foster care stay, little is known about the effect of specific types of substance use on permanency. This study sought to compare the impact of parental methamphetamine use to alcohol use, other drug use, and polysubstance use on the timing of 3 types of permanency: reunification, guardianship, and adoption. Using an entry cohort of 16,620 children who had entered foster care during a 5-year period, competing risks event history models were conducted for each permanency type. Findings showed that, after controlling for several case characteristics, parent illicit drug use significantly impacted the timing of the 3 types of permanency, but alcohol use did not. Methamphetamine, other drug, and polysubstance with methamphetamine use were associated with lower rates of reunification and higher rates of adoption. Guardianship was also predicted by other drug and polysubstance use without methamphetamine; however, methamphetamine use was not associated with guardianship. Notably, the methamphetamine groups comprised the youngest children and had the shortest median time to adoption. Results suggest that type of parental substance use is predictive of permanency exits and that parental illicit drug use may require tailored strategies for improving permanency outcomes. Further implications of the findings are discussed. PMID:25822603

  17. Methamphetamine Accelerates Cellular Senescence through Stimulation of De Novo Ceramide Biosynthesis

    PubMed Central

    Astarita, Giuseppe; Avanesian, Agnesa; Grimaldi, Benedetto; Realini, Natalia; Justinova, Zuzana; Panlilio, Leight V.; Basit, Abdul; Piomelli, Daniele

    2015-01-01

    Methamphetamine is a highly addictive psychostimulant that causes profound damage to the brain and other body organs. Post mortem studies of human tissues have linked the use of this drug to diseases associated with aging, such as coronary atherosclerosis and pulmonary fibrosis, but the molecular mechanism underlying these findings remains unknown. Here we used functional lipidomics and transcriptomics experiments to study abnormalities in lipid metabolism in select regions of the brain and, to a greater extent, peripheral organs and tissues of rats that self-administered methamphetamine. Experiments in various cellular models (primary mouse fibroblasts and myotubes) allowed us to investigate the molecular mechanisms of systemic inflammation and cellular aging related to methamphetamine abuse. We report now that methamphetamine accelerates cellular senescence and activates transcription of genes involved in cell-cycle control and inflammation by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, likely generated through methamphetamine metabolism via cytochrome P450, and involves the recruitment of nuclear factor-κB (NF-κB) to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of NF-κB signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration. The results suggest new therapeutic strategies to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of abstinence treatments. PMID:25671639

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

    PubMed Central

    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

  19. Crystal Clear? The Relationship Between Methamphetamine Use and Sexually Transmitted Infections.

    PubMed

    Mialon, Hugo M; Nesson, Erik T; Samuel, Michael C

    2016-03-01

    Public health officials have cited methamphetamine control as a tool with which to decrease HIV and other sexually transmitted infections, based on previous research that finds a strong positive correlation between methamphetamine use and risky sexual behavior. However, the observed correlation may not be causal, as both methamphetamine use and risky sexual behavior could be driven by a third factor, such as a preference for risky behavior. We estimate the effect of methamphetamine use on risky sexual behavior using monthly data on syphilis diagnoses in California and quarterly data on syphilis, gonorrhea, and chlamydia diagnoses across all states. To circumvent possible endogeneity, we use a large exogenous supply shock in the US methamphetamine market that occurred in May 1995 and a later shock stemming from the Methamphetamine Control Act, which went into effect in October 1997. While the supply shocks had large negative effects on methamphetamine use, we find no evidence that they decreased syphilis, gonorrhea, or chlamydia rates. Our results have broad implications for public policies designed to decrease sexually transmitted infection rates. PMID:25545965

  20. Trends in Production, Trafficking and Consumption of Methamphetamine and Cocaine in Mexico

    PubMed Central

    Brouwer, Kimberly C.; Case, Patricia; Ramos, Rebeca; Magis-Rodríguez, Carlos; Bucardo, Jesus; Patterson, Thomas L.; Strathdee, Steffanie A.

    2009-01-01

    Over the past decade, Mexico has experienced a significant increase in trafficking of cocaine and trafficking and production of methamphetamine. An estimated 70% of U.S. cocaine originating in South America passes through the Central America-Mexico corridor. Mexico-based groups are now believed to control 70%–90% of methamphetamine production and distribution in the U.S. Increased availability of these drugs at reduced prices has led to a parallel rise in local drug consumption. Methamphetamine abuse is now the primary reason for seeking drug user treatment in a number of cities, primarily in northwestern Mexico. While cocaine and methamphetamine use have been linked with the sex trade and high risk behaviors such as shooting gallery attendance and unprotected sex in other settings, comparatively little is known about the risk behaviors associated with use of these drugs in Mexico, especially for methamphetamines. We review historical aspects and current trends in cocaine and methamphetamine production, trafficking and consumption in Mexico, with special emphasis on the border cities of Ciudad Juarez and Tijuana. Additionally, we discuss the potential public health consequences of cocaine use and the recent increase in methamphetamine use, especially in regards to the spread of bloodborne and other infections, in an effort to inform appropriate public health interventions. PMID:16603456

  1. Cold Cook Methods: An Ethnographic Exploration on the Myths of Methamphetamine Production and Policy Implications

    PubMed Central

    Boeri, Miriam W.; Gibson, David; Harbry, Liam

    2011-01-01

    Background Urban legends and myths are prevalent in drug-use environments. However, the distinction between myth and fact is not always clear. We found contradictory claims regarding the emergence of cold cook methods for producing methamphetamine when contrasting user-generated reports with official reports repudiating such methods as myths. Our aim is to open the topic for more academic discussion. Methods We examine cold cook methods of methamphetamine production revealed in our ethnographic study and interviews with former (n=50) and current (n=48) methamphetamine users. Data were collected in the suburbs of a large southeastern city in the United States. We compare the data with reports from law enforcement professionals and public health officials. Results Official reports claim the cold cook method described by users in our study is a myth and does not produce methamphetamine. Small-scale producers sell it as methamphetamine and users claim it has the same effect as methamphetamine. They are charged for possession and distribution of methamphetamine when caught with this drug. It appears the unintended consequences of recent policy aimed to reduce production and use of methamphetamine may be a user-friendly production method. We do not know the health implications at this time. Conclusion We do not make any definitive conclusions on the legitimacy of the stories or myths discussed here but instead suggest that labeling drug stories as myths might lead to dismissing facts that hold partial truth. The subsequent dismissal of cold cook methods among policy and public health officials risks a range of unintended consequences among vulnerable populations. We present our case for more research attention on the myths of methamphetamine production. PMID:19195870

  2. Glial cell modulators attenuate methamphetamine self-administration in the rat

    PubMed Central

    Snider, Sarah E.; Hendrick, Elizabeth S.; Beardsley, Patrick M.

    2013-01-01

    Neuroinflammation induced by activated microglia and astrocytes can be elicited by drugs of abuse. Methamphetamine administration activates glial cells and increases proinflammatory cytokine production, and there is recent evidence of a linkage between glial cell activation and drug abuse-related behavior. We have previously reported that ibudilast (AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), which inhibits phosphodiesterase (PDE) and pro-inflammatory activity, blocks reinstatement of methamphetamine-maintained responding in rats, and that ibudilast and AV1013, an amino analog of ibudilast, which has similar glial-attenuating properties but limited PDE activity, attenuate methamphetamine-induced locomotor activity and sensitization in mice. The present study's objective was to determine whether co-administered ibudilast, AV1013, or minocycline, which is a tetracycline derivative that also suppresses methamphetamine-induced glial activation, would attenuate active methamphetamine i.v. self-administration in Long-Evans hooded rats. Rats were initially trained to press a lever for 0.1 mg/kg/inf methamphetamine according to a FR1 schedule during 2-h daily sessions. Once stable responding was obtained, twice daily ibudilast (1, 7.5, 10 mg/kg), AV1013 (1, 10, 30 mg/kg), or once daily minocycline (10, 30, 60 mg/kg), or their corresponding vehicles, were given i.p. for three consecutive days during methamphetamine (0.001, 0.03, 0.1 mg/kg/inf) self-administration. Ibudilast, AV1013, and minocycline all significantly (p<0.05) reduced responding maintained by 0.03 mg/kg/inf methamphetamine that had maintained the highest level of infusions under vehicle conditions. These results suggest that targeting glial cells may provide a novel approach to pharmacotherapy for treating methamphetamine abuse. PMID:23375937

  3. Discriminative-Stimulus, Subject-rated and Physiological Effects of Methamphetamine in Humans Pretreated with Aripiprazole

    PubMed Central

    Sevak, Rajkumar J.; Vansickel, Andrea R.; Stoops, William W.; Glaser, Paul E. A.; Hays, Lon R.; Rush, Craig R.

    2013-01-01

    Methamphetamine is thought to produce its behavioral effects by releasing dopamine (DA), serotonin (5-HT) and norepinephrine. Results from animal studies support this notion, while results from human laboratory studies have not consistently demonstrated the importance of monoamine systems in the behavioral effects of methamphetamine. Human laboratory procedures of drug-discrimination are well suited to assess neuropharmacological mechanisms of the training drug by studying pharmacological manipulation. In this human laboratory study, six participants with a history of recreational stimulant use learned to discriminate 10 mg oral methamphetamine. After acquiring the discrimination (i.e., ≥80% correct responding on 4 consecutive sessions), the effects of a range of doses of methamphetamine (0, 2.5, 5, 10 and 15 mg), alone and in combination with 0 and 20 mg aripiprazole (a partial agonist at D2 and 5-HT1A receptors), were assessed. Methamphetamine alone functioned as a discriminative stimulus, produced prototypical stimulant-like subject-rated drug effects (e.g., increased ratings of Good Effects, Talkative-Friendly, and Willing to Pay For) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion methamphetamine-appropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of methamphetamine, as well as some of the subject-rated drug effects. These results indicate that monoamine systems likely play a role in the behavioral effects of methamphetamine in humans. Moreover, given the concordance between past results with d-amphetamine and the present findings, d-amphetamine can likely serve as a model for the pharmacological effects of methamphetamine. PMID:21694622

  4. Pharmacological effects of methamphetamine and alpha-PVP vapor and injection.

    PubMed

    Marusich, Julie A; Lefever, Timothy W; Blough, Bruce E; Thomas, Brian F; Wiley, Jenny L

    2016-07-01

    Vaporizing drugs in e-cigarettes is becoming a common method of administration for synthetic cathinones and classical stimulants. Heating during vaporization can expose the user to a cocktail of parent compound and thermolytic degradants, which could lead to different toxicological and pharmacological effects compared to ingesting the parent compound alone via injection or nasal inhalation. This study examined the in vivo toxicological and pharmacological effects of vaporized and injected methamphetamine (METH) and α-pyrrolidinopentiophenone (α-PVP). Male and female ICR mice were administered METH or α-PVP through vapor or i.p. injection. Dose-effect curves were determined for locomotor activity and a functional observational battery (FOB). METH and α-PVP vapor were also evaluated for place preference in male mice. Vapor exposure and injection led to more similarities than differences in toxicological and pharmacological effects. In the FOB, both routes of administration produced typical stimulant effects, and injection also increased some bizarre behaviors (e.g. licking, teeth chattering, darting). Both METH and α-PVP vapor exposure produced conditioned place preference. The two routes of administration had comparable efficacy in locomotor activation, with vapor producing longer lasting effects than injection. Females showed greater METH-induced locomotor activity, and greater incidence of a few somatic signs in the FOB than males. These results explore the toxicology of stimulant vapor inhalation in mice using an e-cigarette device. Despite the current technological and methodological difficulties, studying drug vapor promises to allow determination of toxicological effects of thermolytic products and flavor additives. PMID:27237056

  5. A Rodent “Self-Report” Measure of Methamphetamine Craving? Rat Ultrasonic Vocalizations During Methamphetamine Self-Administration, Extinction, and Reinstatement

    PubMed Central

    Mahler, Stephen V.; Moorman, David E.; Feltenstein, Matthew W.; Cox, Brittney M.; Ogburn, Katelyn B.; Bachar, Michal; McGonigal, Justin T.; Ghee, Shannon M.; See, Ronald E.

    2012-01-01

    Rats emit ultrasonic vocalizations (USVs) in a variety of contexts, and it is increasingly clear that USVs reflect more complex information than mere positive and negative affect states. We sought to examine USVs in a common model of addiction and relapse, the self-administration/reinstatement paradigm, in order to gain insight into subjective states experienced by rats during various types of methamphetamine seeking. We measured three subtypes of “50kHz” USVs [flats, trills, and non-trill frequency modulated USVs (FMs)], as well as long and short duration “22kHz” USVs, during self-administration and extinction training, and during reinstatement elicited by cues, a methamphetamine prime, cues + prime, or the pharmacological stressor yohimbine. During self-administration and extinction, rats emitted many flats and FMs, (and short duration “22kHz” USVs on day 1 of self-administration), but few trills. In contrast, methamphetamine priming injections potently enhanced FMs and trills, and trill production was correlated with the degree of methamphetamine + cue-elicited reinstatement. Cues alone yielded increases only in flat USVs during reinstatement, though a subset of rats displaying strong cue-induced reinstatement also emitted long duration, aversion-related “22kHz” USVs. Although yohimbine administration caused reinstatement, it did not induce “22kHz” USVs in methamphetamine-experienced or methamphetamine-naïve rats (unlike footshock stress, which did induce long duration “22kHz” USVs). These findings demonstrate heterogeneity of rat USVs emitted during different types of methamphetamine seeking, and highlight their potential usefulness for gaining insight into the subjective states of rats in rodent models of drug addiction and relapse. PMID:22940018

  6. Lithium and genetic inhibition of GSK3beta enhance the effect of methamphetamine on circadian rhythms in the mouse.

    PubMed

    Mohawk, Jennifer A; Miranda-Anaya, Manuel; Tataroglu, Ozgur; Menaker, Michael

    2009-03-01

    Lithium, a drug commonly used to treat mood disorders, and the psychostimulant methamphetamine are both capable of altering circadian rhythmicity. Although the actions of lithium on the circadian system are thought to occur through inhibition of glycogen synthase kinase-3beta (GSK3beta), the mechanism by which methamphetamine alters circadian rhythms is unknown. We tested the effects of concurrent methamphetamine and lithium treatment on the circadian wheel-running behavior of mice. Methamphetamine alone lengthened both the active duration and the free-running period of locomotor activity in animals housed in constant conditions. Administering lithium enhanced the period-lengthening effects of methamphetamine in animals housed in constant darkness. This effect was even more pronounced when animals were housed in constant light. Lithium increased both methamphetamine intake and serum levels of methamphetamine, possibly contributing to the effects on circadian behavior. We also tested the effect of methamphetamine in mutant mice possessing only one allele for Gsk3beta. These animals, when treated with methamphetamine, responded like wild-type mice treated with a combination of methamphetamine and lithium, displaying long, free-running rhythms. These data, together with many others in the literature, point to a complicated interaction between the circadian system and the development and possible treatment of psychopathologies such as bipolar disorder and drug addiction. PMID:19339873

  7. Psychosocial and behavioral correlates of depressed mood among female methamphetamine users.

    PubMed

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

    2007-11-01

    Female methamphetamine (meth) users report more depressive symptoms than do males. This study examined psychosocial and behavioral correlates of depressed mood in 146 heterosexual, meth-using women in San Diego, CA. Sixty percent met Beck Depression Inventory (BDI) criteria for moderate to severe depressive symptoms (i.e., higher levels of depressive symptoms); 40% had minimal to mild depressive symptoms (i.e., lower levels of depressive symptoms). The two groups were compared on background characteristics, reasons for meth use, patterns of meth use, psychosocial factors, social and sexual consequences of meth use, and sexual risk behavior. Women with higher levels of depressive symptoms were less likely to be employed, were more likely to use meth to cope with mood, used more grams of meth in a 30-day period, used meth more times per day on a greater number of consecutive days, and were more likely to be binge users of meth. They also scored lower on a measure of self-esteem and higher on measures of impulsivity, social stigma, and social network members' use of meth. In multivariate analyses, lower self-esteem and higher ratings of social network members' use of meth were significant predictors of higher levels of depressive symptoms. Psychosocial and behavioral factors are discussed in terms of treatment protocols for mood regulation and meth abatement in the target population. PMID:18284102

  8. Changes of sperm quality and hormone receptors in the rat testis after exposure to methamphetamine.

    PubMed

    Nudmamud-Thanoi, Sutisa; Sueudom, Wanvipa; Tangsrisakda, Nareelak; Thanoi, Samur

    2016-10-01

    Methamphetamine (METH) is known to damage neurons and induce psychosis. It can also induce apoptosis in seminiferous tubules and affect sperm quality. The present study was carried out to investigate the effect of a rat model of METH addiction on sperm quality and expression of progesterone receptors (PR) and estrogen receptors (ER) in the testis. Sperm quality parameters including sperm motility, sperm morphology and sperm concentration were examined. Protein and gene expressions PR, ERα and ERβ were studied using immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. The percentages of normal sperm motility and normal sperm morphology were significantly decreased in animals receiving METH, especially in escalating dose (ED METH) and escalating dose-binge (ED-binge METH) groups when compared with control. In addition, sperm concentrations in ED METH and ED-binge METH groups were numerically decreased. PR, ERα and ERβ immunoreactive cells were significantly decreased in spermatogonia, spermatogenic cells and especially in Sertoli cells in all METH-treated groups. Furthermore, messenger RNA expression of PR, ERα and ERβ were also significantly decreased in all METH-treated animals. These results indicate that METH can induce abnormal sperm quality. These changes of sperm quality may relate to the reduction of PR, ERα and ERβ expressions in male germ cells and Sertoli cells which are essential for spermatogenesis and development of sperm. PMID:26864947

  9. Age-dependent effects of neonatal methamphetamine exposure on spatial learning.

    PubMed

    Vorhees, Charles V; Skelton, Matthew R; Williams, Michael T

    2007-09-01

    Neonatal rats exposed to (+)-methamphetamine (MA) display spatial learning and reference memory deficits in the Morris water maze. In separate experiments the emergence and permanence of these effects were determined. Twenty litters were used in each experiment, and two male/female pairs/litter received saline or MA (5 mg/kg four times a day) on postnatal days (P) 11-20. In experiment 1, one MA and one saline pair from each litter began testing on either P30 or P40, whereas in experiment 2, testing began on P180 or P360. Animals received trials in a straight swimming channel and then in the Morris maze (acquisition, reversal, and reduced platform phases). In both experiments, MA-treated groups showed impaired learning in the platform trials and impaired reference memory in the probe trials, which were largely independent of age. The P30 and P40 MA impairments were seen on acquisition and reduced platform trials but not on reversal. In the probe trials, MA effects were seen during all phases. The P180 and P360 MA-induced deficits were seen in all phases of the platform trials. In probe trials, deficits were only seen during the reversal and reduced platform phases. The results demonstrate that neonatal MA treatment induces spatial learning and reference memory deficits that emerge early and persist until at least 1 year of age, suggesting permanence. PMID:17762523

  10. Age-dependent effects of neonatal methamphetamine exposure on spatial learning

    PubMed Central

    Vorhees, Charles V.; Skelton, Matthew R.; Williams, Michael T.

    2009-01-01

    Neonatal rats exposed to (+)-methamphetamine (MA) display spatial learning and reference memory deficits in the Morris water maze. In separate experiments the emergence and permanence of these effects were determined. Twenty litters were used in each experiment, and two male/female pairs/litter received saline or MA (5 mg/kg four times a day) on postnatal days (P) 11–20. In experiment 1, one MA and one saline pair from each litter began testing on either P30 or P40, whereas in experiment 2, testing began on P180 or P360. Animals received trials in a straight swimming channel and then in the Morris maze (acquisition, reversal, and reduced platform phases). In both experiments, MA-treated groups showed impaired learning in the platform trials and impaired reference memory in the probe trials, which were largely independent of age. The P30 and P40 MA impairments were seen on acquisition and reduced platform trials but not on reversal. In the probe trials, MA effects were seen during all phases. The P180 and P360 MA-induced deficits were seen in all phases of the platform trials. In probe trials, deficits were only seen during the reversal and reduced platform phases. The results demonstrate that neonatal MA treatment induces spatial learning and reference memory deficits that emerge early and persist until at least 1 year of age, suggesting permanence. PMID:17762523

  11. N-acetylcysteine amide protects against methamphetamine-induced tissue damage in CD-1 mice.

    PubMed

    Zhang, X; Tobwala, S; Ercal, N

    2012-09-01

    Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs, especially the brain. This study evaluated oxidative damage caused by METH to tissues in CD-1 mice and identified a therapeutic drug that could protect against METH-induced toxicity. Male CD-1 mice were pretreated with a novel thiol antioxidant, N-acetylcysteine amide (NACA, 250 mg/kg body weight) or saline. Following this, METH (10 mg/kg body weight) or saline intraperitoneal injections were administered every 2 h over an 8-h period. Animals were killed 24 h after the last exposure. NACA-treated animals exposed to METH experienced significantly lower oxidative stress in their kidneys, livers, and brains than the untreated group, as indicated by their levels of glutathione, malondialdehyde, and protein carbonyl and their catalase and glutathione peroxidase activity. This suggests that METH induces oxidative stress in various organs and that a combination of NACA as a neuro- or tissue-protective agent, in conjunction with current treatment, might effectively treat METH abusers. PMID:22354084

  12. Pretreatment or Posttreatment with Aripiprazole Attenuates Methamphetamine-induced Stereotyped Behavior in Mice

    PubMed Central

    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F. Scott; Kayama, Masaru; Sugimori, Hironobu; Uhl, George R.; Takemura, Motohiko

    2015-01-01

    Aripiprazole is a third-generation atypical antipsychotic and a dopamine D2 receptor partial agonist. In the present study, we investigated whether a single administration of aripiprazole to mice, either as a pretreatment or as a posttreatment, would affect stereotypy induced by methamphetamine (METH). Pretreatment of male ICR mice with aripiprazole (1 or 10 mg/kg, i.p.) attenuated the incidence of METH-induced stereotypical behavior in a dose-dependent manner. Pretreatment of mice with 1 mg/kg aripiprazole produced an increase in the locomotor activity in mice treated with METH compared with mice treated with vehicle plus METH and with 10 mg/kg aripiprazole plus METH. This increase in locomotion is indicative of a rightward shift in the dose–response curve for METH, consistent with a shift in the type of stereotypical behavior observed from biting to sniffing. Aripiprazole posttreatment, after METH-induced stereotypical behavior, was fully expressed and also significantly attenuated overall stereotypy in an aripiprazole dose-dependent manner. These data suggest that the antagonism of METH effects by aripiprazole should be investigated as a potential treatment for acute METH overdose. PMID:26525833

  13. Characterization of binge-dosed methamphetamine-induced neurotoxicity and neuroinflammation

    PubMed Central

    McConnell, Sarah E.A.; O'Banion, M. Kerry; Cory-Slechta, Deborah A.; Olschowka, John A.; Opanashuk, Lisa A.

    2015-01-01

    Methamphetamine (MA) is a potent, highly addictive psychostimulant abused by millions of people worldwide. MA induces neurotoxicity, damaging striatal dopaminergic terminals, and neuroinflammation, with striatal glial activation leading to pro-inflammatory cytokine and reactive oxygen species production. It is unclear whether MA-induced neuroinflammation contributes to MA-induced neurotoxicity. In the current study, we examined the linkage between the time course and dose response of MA-induced neurotoxicity and neuroinflammation. Adult male mice underwent a binge dosing regimen of four injections given every two hours with doses of 2, 4, 6, or 8 mg/kg MA per injection, and were sacrificed after 1, 3, 7, or 14 days. Binge MA treatment dose-dependently caused hyperthermia and induced hypoactivity after one day, though activity returned to control levels within one week. Striatal dopamine (DA) was diminished one day after treatment with at least 4 mg/kg MA, while DA turnover rates peaked after seven days. Although striatal tyrosine hydroxylase and DA transporter levels were also decreased one day after treatment with at least 4 mg/kg MA, they trended toward recovery by day 14. All doses of MA activated striatal glia within one day. While astrocyte activation persisted, microglial activation was attenuated over the two weeks of the study. These findings help clarify the relationship between MA-induced neuroinflammation and neurotoxicity, particularly regarding their temporal and dose-specific dynamics. PMID:26283213

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

    SciTech Connect

    Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael . E-mail: mowens@uams.edu

    2005-12-15

    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.

  15. Conceptualizing Social Recovery: Recovery Routes of Methamphetamine Users

    PubMed Central

    Boeri, Miriam; Gibson, David; Boshears, Paul

    2014-01-01

    The goal of our qualitative study was to gain a phenomenological understanding of routes to recovery from problematic drug use. In-depth interviews and drug histories were collected from 50 former methamphetamine users recruited from a U.S. metropolitan suburb who identified as having had problematic use of this drug in the past. Transcripts of the audio-recorded interviews were coded for common themes regarding types of recovery strategies or tools employed on the route to recovery. The common strategies used for recovery from problematic methamphetamine use in all routes were social in nature and did not necessarily include cessation of all substances. Based on our findings, we suggest a conceptualization of social recovery that focuses on reducing the social harms caused by problematic drug use rather than focusing primarily on cessation of all drug use. Social recovery may be employed as both a treatment strategy and analytical tool. More research is needed to advance the concept of social recovery for intervention, drug policy, and criminal justice implications. PMID:25574504

  16. Epigenetic landscape of amphetamine and methamphetamine addiction in rodents.

    PubMed

    Godino, Arthur; Jayanthi, Subramaniam; Cadet, Jean Lud

    2015-01-01

    Amphetamine and methamphetamine addiction is described by specific behavioral alterations, suggesting long-lasting changes in gene and protein expression within specific brain subregions involved in the reward circuitry. Given the persistence of the addiction phenotype at both behavioral and transcriptional levels, several studies have been conducted to elucidate the epigenetic landscape associated with persistent effects of drug use on the mammalian brain. This review discusses recent advances in our comprehension of epigenetic mechanisms underlying amphetamine- or methamphetamine-induced behavioral, transcriptional, and synaptic plasticity. Accumulating evidence demonstrated that drug exposure induces major epigenetic modifications-histone acetylation and methylation, DNA methylation-in a very complex manner. In rare instances, however, the regulation of a specific target gene can be correlated to both epigenetic alterations and behavioral abnormalities. Work is now needed to clarify and validate an epigenetic model of addiction to amphetamines. Investigations that include genome-wide approaches will accelerate the speed of discovery in the field of addiction. PMID:26023847

  17. Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

    PubMed

    Killinger, Bryan A; Moszczynska, Anna

    2016-02-01

    Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include

  18. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    SciTech Connect

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

  19. Acute respiratory distress syndrome in a woman with heroin and methamphetamine misuse.

    PubMed

    Yeh, P S; Yuan, A; Yu, C J; Kuo, S H; Luh, K T; Yang, P C

    2001-08-01

    Methamphetamine, heroin, and cannabis are three of the most commonly misused drugs in Asia. In Taiwan, cases of misuse of methamphetamine have been increasing. In this paper, we report the case of a 23-year-old woman who had a 10-year history of smoking methamphetamine and intermittent use of heroin for 3 to 4 years. She developed pulmonary toxic effects associated with misuse of heroin and methamphetamine. She was brought to the emergency room because of consciousness disturbance and acute respiratory failure. Her symptoms of rapid progression of refractory hypoxemia, ill-defined densities over both lung fields, and normal pulmonary artery wedge pressure were consistent with acute respiratory distress syndrome. Rapid resolution of infiltrations and improvement of oxygenation were observed after mechanical ventilation with positive end-expiratory pressure support and oxygen therapy. She was discharged on the fifteenth hospital day without any sequela except for mild exertional dyspnea. PMID:11678007

  20. Effect alteration of methamphetamine by amino acids or their salts on ambulatory activity in mice.

    PubMed

    Kuribara, H; Tadokoro, S

    1983-02-01

    Effect alterations of methamphetamine by pretreatment of amino acids or their salts on ambulatory activity in mice were investigated to confirm a fact that certain amino acids, particularly monosodium L-glutamate, are added to methamphetamine by the street users, and that the amino acids augment the effect of methamphetamine. The ambulatory activity of mouse was measured by a tilting-type round activity cage of 25 cm in diameter. The amino acids or their salts tested were monosodium L-glutamate, monosodium L-aspartate, gamma-amino-butyric acid, L-alanine, L-lysine hydrochloride and L-arginine hydrochloride. A single administration of each chemical at doses of 1 and 2 g/kg i.p. did not induce a marked change in the ambulatory activity in mice. Methamphetamine 2 mg/kg s.c. induced an increase in the ambulatory activity with a peak at 40 min after the administration, and the increased ambulatory activity persisted for 3 hr. The ambulation-increasing effect of methamphetamine was augmented by the pretreatment of monosodium L-glutamate and monosodium L-aspartate at 30 min before the methamphetamine administration, while attenuated by the pretreatment of L-lysine hydrochloride and L-arginine hydrochloride in a dose-dependent manner. Gamma-aminobutyric acid and L-alanine did not affect the effect of methamphetamine. Similar augmentation and attenuation in the ambulation-increasing effect of methamphetamine were induced by the pretreatment of sodium bicarbonate 0.9 g/kg i.p. (urinary alkalizer) and ammonium chloride 0.07 g/kg i.p. (urinary acidifier), respectively. The urinary pH level was elevated by the administration of monosodium L-glutamate, monosodium L-aspartate and sodium bicarbonate, and decreased by L-lysine hydrochloride, L-arginine hydrochloride and ammonium chloride. Gamma-aminobutyric acid and L-alanine did not elicit a marked change in the urinary pH level. The present experiment confirms the fact in human that monosodium L-glutamate augments the effect of

  1. The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury.

    PubMed

    Rau, Thomas; Ziemniak, John; Poulsen, David

    2016-01-01

    Methamphetamine is a psychostimulant that was initially synthesized in 1920. Since then it has been used to treat attention deficit hyperactive disorder (ADHD), obesity and narcolepsy. However, methamphetamine has also become a major drug of abuse worldwide. Under conditions of abuse, which involve the administration of high repetitive doses, methamphetamine can produce considerable neurotoxic effects. However, recent evidence from our laboratory indicates that low doses of methamphetamine can produce robust neuroprotection when administered within 12h after severe traumatic brain injury (TBI) in rodents. Thus, it appears that methamphetamine under certain circumstances and correct dosing can produce a neuroprotective effect. This review addresses the neuroprotective potential of methamphetamine and focuses on the potential beneficial application for TBI. PMID:25724762

  2. Application of the ionscan for the detection of methamphetamine and ephedrine in abondoned clandestine laboratories

    NASA Technical Reports Server (NTRS)

    Brown, Patricia A.; Comparin, Jeffrey H.

    1995-01-01

    Clandestine methamphetamine laboratories are prevalent in southern California. The most common encountered synthesis results in vapor release, and drug residue being left behind. The suspected manufacturing area can be vacuumed and/or methanol wiped and screened immediately at the lab site using the Ionscan. Positive results are confirmed by obtaining vacuum sweep samples with subsequent analysis at the DEA Laboratory. This procedure has been utilized successfully for identifying methamphetamine and ephedrine from clandestine laboratories that have been abandoned and/or remodeled.

  3. Low Concentrations of Methamphetamine Can Protect Dopaminergic Cells against a Larger Oxidative Stress Injury: Mechanistic Study

    PubMed Central

    El Ayadi, Amina; Zigmond, Michael J.

    2011-01-01

    Mild stress can protect against a larger insult, a phenomenon termed preconditioning or tolerance. To determine if a low intensity stressor could also protect cells against intense oxidative stress in a model of dopamine deficiency associated with Parkinson disease, we used methamphetamine to provide a mild, preconditioning stress, 6-hydroxydopamine (6-OHDA) as a source of potentially toxic oxidative stress, and MN9D cells as a model of dopamine neurons. We observed that prior exposure to subtoxic concentrations of methamphetamine protected these cells against 6-OHDA toxicity, whereas higher concentrations of methamphetamine exacerbated it. The protection by methamphetamine was accompanied by decreased uptake of both [3H] dopamine and 6-OHDA into the cells, which may have accounted for some of the apparent protection. However, a number of other effects of methamphetamine exposure suggest that the drug also affected basic cellular survival mechanisms. First, although methamphetamine preconditioning decreased basal pERK1/2 and pAkt levels, it enhanced the 6-OHDA-induced increase in these phosphokinases. Second, the apparent increase in pERK1/2 activity was accompanied by increased pMEK1/2 levels and decreased activity of protein phosphatase 2. Third, methamphetamine upregulated the pro-survival protein Bcl-2. Our results suggest that exposure to low concentrations of methamphetamine cause a number of changes in dopamine cells, some of which result in a decrease in their vulnerability to subsequent oxidative stress. These observations may provide insights into the development of new therapies for prevention or treatment of PD. PMID:22022363

  4. [The role of CC-chemokine ligand 2 in the development of psychic dependence on methamphetamine].

    PubMed

    Saika, Fumihiro; Kiguchi, Norikazu; Kishioka, Shiroh

    2015-10-01

    Addiction is described as a chronic neurological disorder associated with plasticity in the mesolimbic system. Recently, it has been suggested that neuroinflammation plays an important role in the induction of neuronal plasticity and the formation of pathogenesis in chronic neurological disorders. Therefore, we examined the role of CC-chemokine ligand 2 (CCL2), a proinflammatory chemokine, in the development of psychic dependence on methamphetamine. In mice treated with methamphetamine, CCL2 mRNA was significantly increased in prefrontal cortex and nucleus accumbens. Moreover, phosphorylated tyrosine hydroxylase serine40 (pTH Ser40) levels in the ventral tegmental area (VTA) were increased by methamphetamine. Similarly, pTH Ser40 levels in the VTA were also increased by the intracerebroventricular administration of recombinant CCL2. The increment of pTH Ser40 levels in the VTA by methamphetamine was attenuated by RS504393, a selective CC-chemokine receptor 2 (CCR2) antagonist, indicating that the increased CCL2 activates the brain reward system via CCR2 activation. In the conditioned place preference test, methamphetamine produced place preference in a dose-dependent manner, which was attenuated by RS504393. These results suggest that the activation of the brain reward system via CCL2-CCR2 pathway plays an important role in the development of psychic dependence on methamphetamine. PMID:26946780

  5. Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial

    PubMed Central

    Elkashef, Ahmed; Kahn, Roberta; Yu, Elmer; Iturriaga, Erin; Li, Shou-Hua; Anderson, Ann; Chiang, Nora; Ait-Daoud, Nassima; Weiss, David; McSherry, Frances; Serpi, Tracey; Rawson, Richard; Hrymoc, Mark; Weis, Dennis; McCann, Michael; Pham, Tony; Stock, Christopher; Dickinson, Ruth; Campbell, Jan; Gorodetzky, Charles; Haning, William; Carlton, Barry; Mawhinney, Joseph; Li, Ming D.; Johnson, Bankole A.

    2012-01-01

    Aims Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled outpatient trial tested topiramate for treating methamphetamine addiction. Design Participants (N=140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 50 mg/day to the target maintenance of 200 mg/day in weeks 6–12 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. Setting The trial was conducted at eight medical centers in the United States. Participants One hundred forty methamphetamine-dependent adults took part in the trial. Measurements The primary outcome was abstinence from methamphetamine during weeks 6 – 12. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables. Findings In the intent-to-treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 6–12. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer-rated severity of dependence scores significantly. Subjects with negative urine before randomization (N=26) had significantly greater abstinence on topiramate versus placebo during study weeks 6–12. Topiramate was safe and well tolerated. Conclusions Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent. PMID:22221594

  6. EFFECTS OF PRENATAL METHAMPHETAMINE EXPOSURE ON BEHAVIORAL AND COGNITIVE FINDINGS AT 7.5 YEARS

    PubMed Central

    Diaz, Sabrina D.; Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn A.; Grotta, Sheri Della; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

    2014-01-01

    Objective To examine child behavioral and cognitive outcomes after prenatal exposure to methamphetamine. Study design 412 mother-infant pairs (204 methamphetamine-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. The 151 children exposed to methamphetamine and 147 comparisons who attended the 7.5 year visit were included. Exposure was determined by maternal self-report and/or positive meconium toxicology. Maternal interviews assessed behavioral and cognitive outcomes using the Conner’s Parent Rating Scale – Revised: Short Form (CPRS-R:S). Results After adjusting for covariates, children exposed to methamphetamine had significantly higher cognitive problems subscale scores than comparisons and were 2.8 times more likely to have cognitive problems scores that were above average on the CPRS-R:S No association between prenatal methamphetamine exposure and behavioral problems, measured by the oppositional, hyperactivity and ADHD Index subscales, were found. Conclusion Prenatal methamphetamine exposure was associated with increased cognitive problems which may impact academic achievement and lead to increased negative behavioral outcomes. PMID:24630350

  7. Improved Chiral Separation of Methamphetamine Enantiomers Using CSP-LC-MS-MS.

    PubMed

    Ward, Lauren F; Enders, Jeffrey R; Bell, David S; Cramer, Hugh M; Wallace, Frank N; McIntire, Gregory L

    2016-05-01

    To determine the true enantiomeric composition of methamphetamine urine drug testing results, chiral separation of dextro (d) and levo (l) enantiomers is necessary. While enantiomeric separation of methamphetamine has traditionally been accomplished using gas chromatography-mass spectrometry (GC-MS), chiral separation ofd- andl-methamphetamine by chiral stationary phase (CSP) liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS) has proved more reliable. Chirally selective detection of methamphetamine by GC-MS is often performed usingl-N-trifluoroacetyl-prolyl chloride (TPC).l-TPC, a chiral compound, is known to have impurities that can affect the chiral composition percentages of the methamphetamine sample, potentially leading to inaccurate patient results. The comparative analysis of the samples run by GC and LC methods showed preferential bias of the GC method for producing error rates, consistent with previous research, of 8-19%. The CSP-LC-MS-MS method produces percent deviation errors of <2%. Additionally, the GC method failed to produce results that were 100%d- orl-isomer even for enantiomerically pure standards. A higher rate ofd- andl-methamphetamine isomer racemization is seen in samples when analyzed by GC-MS usingl-TPC-derivatizing agent. This racemization is not seen when these samples are tested with CSP-LC-MS-MS. Thus, a more accurate method of enantiomeric analysis is provided by CSP-LC-MS-MS. PMID:26869715

  8. In vivo imaging of mitochondrial function in methamphetamine-treated rats.

    PubMed

    Shiba, Takeshi; Yamato, Mayumi; Kudo, Wataru; Watanabe, Toshiaki; Utsumi, Hideo; Yamada, Ken-ichi

    2011-08-01

    Abuse of the powerfully addictive psychostimulant, methamphetamine, occurs worldwide. Recent studies have suggested that methamphetamine-induced dopaminergic neurotoxicity is related to oxidative stress. In response to nerve activation, the mitochondrial respiratory chain is rapidly activated. The enhancement of mitochondrial respiratory chain activation may induce oxidative stress in the brain. However, there is little experimental evidence regarding the mitochondrial function after methamphetamine administration in vivo. Here, we evaluated whether a single administration of methamphetamine induces ATP consumption and overactivation of mitochondria. We measured mitochondrial function in two different ways: by monitoring oxygen partial pressure using an oxygen-selective electrode, and by imaging of redox reactions using a nitroxyl radical (i.e., nitroxide) coupled with Overhauser-enhanced magnetic resonance imaging (OMRI). A single administration of methamphetamine to Wistar rats induced dopaminergic nerve activation, ATP consumption and an increase in mitochondrial respiratory chain function in both the striatum and cortex. Furthermore, antioxidant TEMPOL prevented the increase in mitochondrial oxidative damage and methamphetamine-induced sensitization. These findings suggest that energy-supplying reactions after dopaminergic nerve activation are associated with oxidative stress in both the striatum and cortex, leading to abnormal behavior. PMID:21624473

  9. The relative reinforcing strength of methamphetamine and D-amphetamine in monkeys self-administering cocaine.

    PubMed

    Lile, Joshua A; Charnigo, Richard J; Nader, Michael A

    2013-09-01

    Epidemiological data indicate that rates of methamphetamine misuse surpass those of D-amphetamine, but self-administration research in animals and humans has not typically demonstrated differences in their reinforcing effects. The present study used a within-session, exponentially increasing progressive-ratio schedule and extended-access conditions to assess the relative reinforcing strength of D-amphetamine and methamphetamine in rhesus monkeys (n=5) trained to self-administer cocaine. A range of doses of methamphetamine (0.003-0.1 mg/kg/injection), D-amphetamine (0.003-0.1 mg/kg/injection), and cocaine (0.003-0.3 mg/kg/injection) was tested to capture the ascending and descending limbs of the dose-effect functions. Each drug functioned as a reinforcer, but the peak number of self-administered D-amphetamine injections was significantly lower compared with methamphetamine and cocaine; the peak number of self-administered injections of cocaine and methamphetamine did not differ. Although differences in availability and other social factors likely impact relative rates of abuse, the present data suggest that the greater reinforcing strength of methamphetamine contributes to its increased use compared with D-amphetamine. PMID:23907377

  10. Association Study of Two Cannabinoid Receptor Genes, CNR1 and CNR2, with Methamphetamine Dependence

    PubMed Central

    Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Ujike, H

    2011-01-01

    Several studies have suggested that the endocannabinoid system plays significant roles in the vulnerability to psychiatric disorders including drug abuse. To examine the possible association of the CNR1 and CNR2 genes, which encode cannabinoid receptors CB1 and CB2, with methamphetamine dependence, we investigated three single nucleotide polymorphisms (SNPs) (rs806379, rs1535255, rs2023239) in intron 2 of the CNR1 gene and a nonsynonymous SNP, Q63R, in the CNR2 gene. The study samples consisted of 223 patients with methamphetamine dependence and 292 age- and sex- matched controls. There were no significant differences between the patients and controls in genotypic or allelic distribution of any SNP of the CNR1 and CNR2 genes. We also analyzed the clinical features of methamphetamine dependence. Rs806379 of the CNR1 gene showed a significant association with the phenotype of latency of psychosis after the first consumption of methamphetamine. Patients with the T allele or T-positive genotypes (T/T or A/T) may develop a rapid onset of psychosis after methamphetamine abuse. The present study suggests a possibility that genetic variants of the CNR1 gene may produce a liability to the complication of psychotic state after abuse of methamphetamine; however, our findings need to be confirmed by future replications. PMID:21886587

  11. Methamphetamine-induced decrease in tryptophan hydroxylase activity: role of 5-hydroxytryptaminergic transporters.

    PubMed

    Fleckenstein, A E; Beyeler, M L; Jackson, J C; Wilkins, D G; Gibb, J W; Hanson, G R

    1997-04-18

    Methamphetamine-induced 5-hydroxytryptaminergic neuronal damage purportedly involves transport of newly released dopamine from extracellular spaces into 5-hydroxytryptaminergic terminals. This hypothesis is based primarily on findings that dopamine is required for, whereas 5-hydroxytryptamine (5-HT) uptake inhibitors prevent, methamphetamine-induced deficits in 5-hydroxytryptaminergic neuronal function. This hypothesis is not, however, supported by findings presented in this study that 5-hydroxytryptaminergic neuronal damage, induced by p-chloroamphetamine, does not decrease [3H]dopamine uptake into rat brain synaptosomes prepared from 5-HT-transporter-containing tissue. Moreover, despite having greater affinity for the 5-HT transporter, citalopram has an IC50 for [1H]dopamine transport into these synaptosomal preparations that is considerably greater than that of fluoxetine. These data suggest that 5-HT transporters may not effect dopamine uptake and thereby methamphetamine-induced 5-hydroxytryptaminergic neuronal damage. Other possible mechanisms related to 5-HT uptake inhibitor attenuation of methamphetamine-induced deficits were investigated. Fluoxetine pretreatment prevented the methamphetamine-induced decrease in tryptophan hydroxylase activity: this effect cannot be attributed to altered body temperatures or brain concentrations of methamphetamine which suggests that neither, per se, is sufficient to impair 5-hydroxytryptaminergic neuronal function. PMID:9145769

  12. Methamphetamine and cannabis abuse in adolescence: a quasi-experimental study on specific and long-term neurocognitive effects

    PubMed Central

    Cuzen, Natalie L; Koopowitz, Sheri-Michelle; Ferrett, Helen L; Stein, Dan J; Yurgelun-Todd, Deborah

    2015-01-01

    Objectives Methamphetamine abuse affects brain structure and function. Although methamphetamine and cannabis are commonly abused together, few studies have investigated the differential neurocognitive consequences of methamphetamine abuse with or without cannabis. Furthermore, the effects of drug use on the developing adolescent brain remain poorly understood. We compared neurocognitive function between adolescents with ‘pure’ methamphetamine abuse, those with comorbid methamphetamine and cannabis abuse, and healthy controls at baseline and follow-up. Methods Individuals residing in the greater Cape Town region, between the ages of 13 and 18 years, were recruited into either Methamphetamine only group (Meth-only; n=10), Methamphetamine and cannabis group (Meth-cann; n=10) or healthy control (n=20) groups using a quasi-experimental design. All participants underwent a comprehensive neurocognitive assessment. Substance-use variables and psychiatric symptom counts were also recorded. A portion of the Meth-only and control participants completed 12-month follow-up assessments. Results While the Meth-cann group demonstrated widespread neurocognitive deficits at baseline, these deficits were restricted to the self-monitoring domain in the Meth-only group at baseline and at follow-up. Conclusions Methamphetamine abuse with cannabis abuse is associated with significantly more neurocognitive impairment than methamphetamine abuse alone, and such deficits may be enduring. PMID:25636791

  13. Randomized Trial of Intensive Motivational Interviewing for Methamphetamine Dependence

    PubMed Central

    Polcin, Douglas L.; Bond, Jason; Korcha, Rachael; Nayak, Madhabika B.; Galloway, Gantt P.; Evans, Kristy

    2014-01-01

    An intensive, 9-session Motivational Interviewing (IMI) intervention was assessed using a randomized clinical trial of 217 methamphetamine (MA) dependent persons. Intensive motivational interviewing (IMI) was compared with a standard single standard session of MI (SMI) combined with eight nutrition education sessions. Interventions were delivered weekly over two months. All study participants also received standard outpatient group treatment three times per week. Both study conditions showed significant decreases in MA use and ASI drug scores, but there were no significant differences between the two conditions. However, reductions in ASI psychiatric severity scores and days of psychiatric problems during the past 30 days were found for clients in the IMI condition but not SMI. SMI may be equally beneficial to IMI in reducing MA use and problem severity, but IMI may help alleviate co-occurring psychiatric problems that are unaffected by shorter MI interventions. Additional studies are needed to assess the problems, populations, and contexts for which IMI is effective. PMID:25115166

  14. Methamphetamine-using felons: Psychosocial and behavioral characteristics

    PubMed Central

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

    2010-01-01

    Methamphetamine (meth) users with felony convictions may be important vectors in the HIV/AIDS pandemic because of their drug and sexual risk histories. This study gathered personal, psychosocial, and behavioral data from 450 HIV-negative, heterosexually-identified, meth-using men and women. Significant differences were found between felons and non-felons in meth use patterns, contexts and reasons for use, involvement of social networks in meth use, and certain psychosocial and sexual risk variables. Our findings suggest that targeting meth use patterns and motivations, social networks, and sexual risk behaviors of meth-using felons may help to reduce HIV/AIDS transmission in and outside the prison system. PMID:18214720

  15. Methamphetamine and MDMA (ecstasy) neurotoxicity: 'of mice and men'.

    PubMed

    Itzhak, Yossef; Achat-Mendes, Cindy

    2004-05-01

    Methamphetamine (METH) and 3,4-meythylenedioxymethamphetamine (MDMA; 'ecstasy') are currently major drugs of abuse. One of the major concerns of amphetamines abuse is their potential neurotoxic effect on dopaminergic and serotonergic neurons. Although data from human studies are somewhat limited, compelling evidence suggests that these drugs cause neurotoxicity in rodents and primates. Recent studies in transgenic and knockout mice identified the role of dopamine transporters, nitric oxide, apoptotic proteins, and inflammatory cytokines in amphetamines neurotoxicity. Further research into the mechanisms underlying the dopaminergic and serotonergic neurotoxicity and the behavioral corollaries of these neuronal insults could facilitate our understanding of the consequences of human abuse of METH and MDMA on cognition, drug-seeking behavior, extinction and relapse. PMID:15370888

  16. Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

    PubMed Central

    Yu, Shaobin; Zhu, Ling; Shen, Qiang; Bai, Xue; Di, Xuhui

    2015-01-01

    Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which 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, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level. PMID:25861156

  17. The need for speed: an update on methamphetamine addiction

    PubMed Central

    Barr, Alasdair M.; Panenka, William J.; MacEwan, G. William; Thornton, Allen E.; Lang, Donna J.; Honer, William G.; Lecomte, Tania

    2006-01-01

    The psychostimulant methamphetamine (MA) is a highly addictive drug that has surged in popularity over the last decade in North America. A burgeoning number of clandestine drug laboratories has led to dramatic increases in MA production, which have resulted in significant public health, legal and environmental problems. Current evidence indicates that exposure to MA is neurotoxic, and neuroimaging studies confirm that long-term use in humans may lead to extensive neural damage. These physiological changes are commonly associated with persistent forms of cognitive impairment, including deficits in attention, memory and executive function. In the present review, we provide a comprehensive description of the factors relating to MA use and the major health-related consequences, with an emphasis on MA-induced psychosis. It is hoped that increased knowledge of MA abuse will provide the basis for future treatment strategies. PMID:16951733

  18. Methamphetamine compromises gap junctional communication in astrocytes and neurons.

    PubMed

    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

  19. Racial disparities in methamphetamine-associated intracerebral hemorrhage

    PubMed Central

    Vento, Megan A.; Ing, Marissa M.; Seto, Todd B.

    2015-01-01

    Objective: To assess racial disparities in the prevalence of methamphetamine-associated intracerebral hemorrhage (Meth-ICH) among Native Hawaiians and other Pacific Islanders (NHOPI). Methods: Prospectively collected data from an ongoing, multiethnic, single-center cohort study were analyzed. The inclusion criteria for the cohort study required that patients be adult (age 18 years or older) residents of Hawaii with nontraumatic spontaneous intracerebral hemorrhage (ICH). Patients of race other than white, Asian, or NHOPI were excluded. Determination of Meth-ICH was made prospectively by positive urine toxicology result and lack of other clinically suspected ICH etiology. Prevalence of Meth-ICH among NHOPI was compared with that of white and Asian patients. Results: A total of 193 patients (white 16%, Asian 61%, NHOPI 23%) were analyzed. NHOPI were younger than white (54 ± 15 vs 68 ± 15 years, respectively, p = 0.0001) and Asian (vs 65 ± 16 years, p = 0.0001) patients. Overall, 25 (13%) Meth-ICHs (mean age: 49 ± 6 years, range: 33–56 years) were identified. NHOPI had higher prevalence of Meth-ICH compared with white (24% vs 0%, respectively, p = 0.003) and Asian (vs 12%, p = 0.046) patients. The observed age differences between the racial groups persisted even after excluding the Meth-ICH group (p < 0.01 for all comparison). Conclusions: NHOPI have higher prevalence of Meth-ICH compared with white and Asian patients. However, the age disparity is not entirely driven by methamphetamine abuse. PMID:25663228

  20. "Nothing Is Free": A Qualitative Study of Sex Trading Among Methamphetamine Users in Cape Town, South Africa.

    PubMed

    Watt, Melissa H; Kimani, Stephen M; Skinner, Donald; Meade, Christina S

    2016-05-01

    South Africa is facing an established epidemic of methamphetamine, known locally as "tik." Globally, methamphetamine has been linked to high rates of sexual risk behaviors, including sex trading. The goal of this study was to qualitatively examine the experiences of sex trading among methamphetamine users in Cape Town, South Africa. Individual in-depth interviews were conducted with 30 active methamphetamine users (17 men and 13 women) recruited from the community. Interviews were conducted in local languages using a semi-structured guide that included questions on sex trading experiences and perceptions of sex trading among methamphetamine users. Interviews were audio-recorded, transcribed, and analyzed using analytic memos and coding with constant comparison techniques. The data revealed that in a setting of high levels of addiction and poverty, sex was an important commodity for acquiring methamphetamine. Women were more likely to use sex to acquire methamphetamine, but men reported opportunistic cases of trading sex for methamphetamine. Four models of sex trading emerged: negotiated exchange, implicit exchange, relationships based on resources, and facilitating sex exchange for others. The expectation of sex trading created a context in which sexual violence against female methamphetamine users was common. Multiple sexual partners and inconsistent condom use in acts of sex trading put methamphetamine users at high risk of HIV. Interventions in this setting should address addiction, which is the primary driver of sex trading among methamphetamine users. Harm reduction interventions may include education about HIV and other sexually transmitted infections, availability of condoms and HIV testing, and sexual violence prevention. PMID:25567071

  1. Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence.

    PubMed

    Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

    2016-03-01

    We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [(11)C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, p<0.0001) and correlated with severity and recency of drug use and with cognitive impairment and withdrawal symptoms. Mean [(11)C]-(+)-dihydrotetrabenazine binding levels in the subgroup of methamphetamine users who could remain abstinent ~10 days following last use (n=17) were normal at the follow-up scan. Our imaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication. PMID:26321315

  2. The mental health experiences and needs of methamphetamine users in Cape Town: A mixed methods study

    PubMed Central

    Watt, Melissa H.; Myers, Bronwyn; Towe, Sheri L.; Meade, Christina S.

    2015-01-01

    Background South Africa has a burgeoning problem of methamphetamine use, particularly in the Western Cape. 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 South Africa. Objective To describe the mental health experiences and needs of out-of-treatment methamphetamine users in Cape Town. Methods Active methamphetamine users were recruited using respondent driven sampling techniques. Eligible participants (n=360) completed a computer-assisted assessment and clinical interview, where they provided data on mental health symptoms and treatment seeking behaviour. A subset of 30 participants completed qualitative in-depth interviews where they provided narrative accounts of their mental health experiences and needs. Analysis of the mixed-methods data was conducted using a concurrent triangulation strategy, whereby both methods contributed equally to the analysis and were used for cross-validation. Results About half of survey participants met screening criteria for depression and traumatic stress, and there were some indications of paranoia. Using substances to cope with psychological distress was common, with participants talking about using methamphetamine to numb their feelings or forget stressful memories. One-third of women and 13% of men had previously tried to commit suicide. Despite the huge mental health burden in this population, very few had ever received mental health treatment. Conclusion The data indicates a need for integrated care that addresses both substance use and psychiatric needs in this population. Mental health and drug treatment services targeting methamphetamine users should include a concerted focus on suicide prevention. PMID:26449695

  3. Actigraphy-Based Sleep Parameters During the Reinstatement of Methamphetamine Self-Administration in Rhesus Monkeys

    PubMed Central

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

    2016-01-01

    The objective of the present study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetamine and stimulus light (drug-conditioned stimulus presented during drug self-administration) withheld until subjects reached extinction criteria. Drug- and cue-induced reinstatement effects were evaluated after i.v. non-contingent priming injections of methamphetamine (0.03, 0.1 or 0.3 mg/kg). Activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline nighttime activity parameters) and throughout the protocol. Although methamphetamine self-administration did not significantly affect nighttime activity compared to baseline, sleep-like parameters were improved during extinction compared to self-administration maintenance. Priming injection of 0.1 mg/kg methamphetamine, but not 0.03 or 0.3 mg/kg, induced significant reinstatement effects. These behavioral responses were accompanied by nighttime outcomes, with increased sleep fragmentation and decreased sleep efficiency in the night following 0.1 mg/kg methamphetamine-induced reinstatement. In the absence of both drug and drug-paired cues (extinction conditions), nighttime activity decreased compared to self-administration maintenance. Additionally, effective reinstatement conditions impaired sleep-like measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity. PMID:26882419

  4. Association Between 5HT1b Receptor Gene and Methamphetamine Dependence

    PubMed Central

    Ujike, H; Kishimoto, M; Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N

    2011-01-01

    Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis. PMID:21886584

  5. Rapid Quantification of Methamphetamine: Using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Chemometrics

    PubMed Central

    Hughes, Juanita; Ayoko, Godwin; Collett, Simon; Golding, Gary

    2013-01-01

    In Australia and increasingly worldwide, methamphetamine is one of the most commonly seized drugs analysed by forensic chemists. The current well-established GC/MS methods used to identify and quantify methamphetamine are lengthy, expensive processes, but often rapid analysis is requested by undercover police leading to an interest in developing this new analytical technique. Ninety six illicit drug seizures containing methamphetamine (0.1%–78.6%) were analysed using Fourier Transform Infrared Spectroscopy with an Attenuated Total Reflectance attachment and Chemometrics. Two Partial Least Squares models were developed, one using the principal Infrared Spectroscopy peaks of methamphetamine and the other a Hierarchical Partial Least Squares model. Both of these models were refined to choose the variables that were most closely associated with the methamphetamine % vector. Both of the models were excellent, with the principal peaks in the Partial Least Squares model having Root Mean Square Error of Prediction 3.8, R2 0.9779 and lower limit of quantification 7% methamphetamine. The Hierarchical Partial Least Squares model had lower limit of quantification 0.3% methamphetamine, Root Mean Square Error of Prediction 5.2 and R2 0.9637. Such models offer rapid and effective methods for screening illicit drug samples to determine the percentage of methamphetamine they contain. PMID:23936058

  6. Physical and Psychological Harms and Health Consequences of Methamphetamine Use amongst a Group of New Zealand Users

    ERIC Educational Resources Information Center

    Butler, Rachael; Wheeler, Amanda; Sheridan, Janie

    2010-01-01

    Methamphetamine has become a drug of concern in many countries. This qualitative study reports on the historical and current psychological and physical health of a group of methamphetamine users in Auckland, New Zealand in 2004, most of whom were in drug treatment. Participants reported they had experienced a range of physical health problems…

  7. The study of metabolite-to-parent drug ratios of methamphetamine and methylenedioxymethamphetamine in hair.

    PubMed

    Han, Eunyoung; Park, Yonghoon; Yang, Wonkyung; Lee, Jaesin; Lee, Sooyeun; Kim, Eunmi; Lim, Miae; Chung, Heesun

    2006-09-12

    The metabolite-to-parent drug ratios were determined in the hair of 2444 methamphetamine (MA) abusers who had produced MA-positive hair results from 2001 to May 2005 and in the hair of 53 ecstasy abusers who had produced positive methylenedioxymethamphetamine (MDMA) hair results from 2002 to May 2005. For the hair analyses, hair strands were washed, cut into small pieces and extracted for 20 h in 1 mL methanol containing 1% HCl. Drugs in the extract were determined by gas chromatography-mass spectrometry (GC-MS) using selective ion monitoring after derivatization with trifluoroacetic anhydride. The six range groups were divided as follows on the basis of MA concentrations in hair (n = 2389): 0.5-5 ng/mg (n = 950), 5-10 ng/mg (n = 582), 10-20 ng/mg (n = 503), 20-30 ng/mg (n = 160), 30-40 ng/mg (n = 80), more than 40 ng/mg (n = 114) to assess the correlations between MA concentrations and metabolite-to-parent drug ratios. In groups of higher MA concentrations, lower ratios of AP/MA were found, and there was a statistically significant difference among six range groups. Comparisons of age groups (tens, twenties, thirties, forties, fifties, and sixties) and male and female subjects for the ratios of AP/MA showed a statistically significant difference. The detection of metabolites and the parent drug with reasonable ratios was found to be a useful indicator for distinguishing internal drug incorporation from external contamination. In our study, MA users can produce 0.4-116% (mean = 9%) of amphetamine (AP) concentrations in hair, and ecstasy users 1-110% (mean = 12%) of methylenedioxyamphetamine (MDA) in appropriately washed hair samples. PMID:16870374

  8. Methamphetamine Consumption Inhibits Pair Bonding and Hypothalamic Oxytocin in Prairie Voles.

    PubMed

    Hostetler, Caroline M; Phillips, Tamara J; Ryabinin, Andrey E

    2016-01-01

    Methamphetamine (MA) abuse has been linked to violence, risk-taking behaviors, decreased sexual inhibition, and criminal activity. It is important to understand mechanisms underlying these drug effects for prevention and treatment of MA-associated social problems. Previous studies have demonstrated that experimenter-administered amphetamine inhibits pair bonding and increases aggression in monogamous prairie voles. It is not currently known whether similar effects on social behaviors would be obtained under conditions during which the drug is voluntarily (actively) administered. The current study investigated whether MA drinking affects pair bonding and what neurocircuits are engaged. In Experiment 1, we exposed male and female voles to 4 days each of 20 and 40 mg/L MA under a continuous 2-bottle choice (2BC) procedure. Animals were housed either singly or in mesh-divided cages with a social partner. Voles consumed MA in a drinking solution, but MA drinking was not affected by either sex or housing condition. In Experiment 2, we investigated whether MA drinking disrupts social bonding by measuring aggression and partner preference formation following three consecutive days of 18-hour/day access to 100 mg/L MA in a 2BC procedure. Although aggression toward a novel opposite-sex animal was not affected by MA exposure, partner preference was inhibited in MA drinking animals. Experiment 3 examined whether alterations in hypothalamic neuropeptides provide a potential explanation for the inhibition of partner preference observed in Experiment 2. MA drinking led to significant decreases in oxytocin, but not vasopressin, in the paraventricular nucleus of the hypothalamus. These experiments are the first investigation into how voluntary pre-exposure to MA affects the development of social attachment in a socially monogamous species and identify potential neural circuits involved in these effects. PMID:27380172

  9. Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats

    PubMed Central

    Miller, ML; Vaillancourt, BD; Wright, MJ; Aarde, SM; Vandewater, SA; Creehan, KM; Taffe, MA

    2011-01-01

    Background Some epidemiological and cessation studies suggest physical exercise attenuates or prevents recreational drug use in humans. Preclinical studies indicate wheel activity reduces cocaine self-administration in rats; this may, however, require the establishment of compulsive wheel activity. Methods Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self-administration were examined in male Wistar and Sprague Dawley rats with negligible prior wheel experience. Wistar rats self-administered METH (0.05 mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an activity wheel during sessions 1–14, 8–21 or 15–21. Control rats which did not self-administer METH had access to an activity wheel during sessions 1–14, 8–21 or 15–28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1 for 14 sessions with either concurrent access to a locked or an unlocked activity wheel. Results METH self-administration was lower when the wheel was available concurrently from the start of self-administration training in both strains, even though Sprague Dawley rats self-administered twice as many METH infusions and ran one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated after 7 or 14 days had no effect on METH self-administration in Wistar rats. Wheel activity was significantly reduced in these groups compared with the group with concurrent wheel and METH access for the first 14 sessions. Conclusions These data show METH self-administration is reduced by exercise if initiated from the start of self-administration and that prior METH self-administration experience interferes with the value of exercise as a reinforcer. PMID:21899959

  10. Methamphetamine exposure during pregnancy at pharmacological doses produces neurodevelopmental and behavioural effects in rat offspring.

    PubMed

    McDonnell-Dowling, Kate; Donlon, Michelle; Kelly, John P

    2014-06-01

    In recent years methamphetamine (MA) use has become more prevalent, and of particular concern is its growing popularity of MA among women of childbearing age. However, to date, studies examining MA effects on the developing offspring in laboratory animals are limited. Thus, the aim of this study was to determine if in utero MA exposure in rats at pharmacological doses can have a negative impact on neonatal neurodevelopment and behaviour. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (0, 0.625, 1.25, 2.5mg/kg) once daily via oral gavage from gestational day 7 to 21. Maternal body weight, food and water consumption were recorded daily. A range of standard neurodevelopment parameters was examined in the offspring during the neonatal period. There were no neurodevelopmental deficits observed with offspring exposed to 0.625mg/kg MA, in fact, there were enhancements of neurodevelopment in some parameters at this low dose. However, exposure to the 1.25mg/kg MA dose resulted in significant impairments in surface righting reflex and forelimb grip in both sexes. Exposure to the 2.5mg/kg MA dose resulted in a significant reduction in ano-genital distance in males, and in both sexes resulted in delayed fur appearance and eye opening, impairments in surface righting reflex and negative geotaxis, and a reduction in body length. In conclusion, this study demonstrates that pharmacologically relevant doses of MA can have profound dose-related effects on neonatal outcome. If extrapolated to the clinical scenario this will give cause for concern regarding the risks associated with this drug of abuse at relatively low doses. PMID:24667147

  11. Methamphetamine Consumption Inhibits Pair Bonding and Hypothalamic Oxytocin in Prairie Voles

    PubMed Central

    Hostetler, Caroline M.; Phillips, Tamara J.; Ryabinin, Andrey E.

    2016-01-01

    Methamphetamine (MA) abuse has been linked to violence, risk-taking behaviors, decreased sexual inhibition, and criminal activity. It is important to understand mechanisms underlying these drug effects for prevention and treatment of MA-associated social problems. Previous studies have demonstrated that experimenter-administered amphetamine inhibits pair bonding and increases aggression in monogamous prairie voles. It is not currently known whether similar effects on social behaviors would be obtained under conditions during which the drug is voluntarily (actively) administered. The current study investigated whether MA drinking affects pair bonding and what neurocircuits are engaged. In Experiment 1, we exposed male and female voles to 4 days each of 20 and 40 mg/L MA under a continuous 2-bottle choice (2BC) procedure. Animals were housed either singly or in mesh-divided cages with a social partner. Voles consumed MA in a drinking solution, but MA drinking was not affected by either sex or housing condition. In Experiment 2, we investigated whether MA drinking disrupts social bonding by measuring aggression and partner preference formation following three consecutive days of 18-hour/day access to 100 mg/L MA in a 2BC procedure. Although aggression toward a novel opposite-sex animal was not affected by MA exposure, partner preference was inhibited in MA drinking animals. Experiment 3 examined whether alterations in hypothalamic neuropeptides provide a potential explanation for the inhibition of partner preference observed in Experiment 2. MA drinking led to significant decreases in oxytocin, but not vasopressin, in the paraventricular nucleus of the hypothalamus. These experiments are the first investigation into how voluntary pre-exposure to MA affects the development of social attachment in a socially monogamous species and identify potential neural circuits involved in these effects. PMID:27380172

  12. Text messaging reduces HIV risk behaviors among methamphetamine-using men who have sex with men.

    PubMed

    Reback, Cathy J; Grant, Deborah Ling; Fletcher, Jesse B; Branson, Catherine M; Shoptaw, Steven; Bowers, Jane Rohde; Charania, Mahnaz; Mansergh, Gordon

    2012-10-01

    Text-messaging interventions present a novel approach for targeting high-risk men who have sex with men (MSM) who may not respond to or may be difficult to reach for face-to-face or site-based interventions. Project Tech Support (N = 52) was an open label pilot study testing the feasibility and utility of a text-messaging intervention to reduce methamphetamine use and high-risk sexual behaviors among out-of-treatment MSM. Participants in the two-week intervention received social support and health education text messages transmitted in real-time. At follow-up, there were significant decreases in frequency of methamphetamine use and unprotected sex while on methamphetamine (both p < 0.01), and a significant increase in self-reported abstinence from methamphetamine use (13.3 % vs. 48.9 %; p < 0.001). Additionally, participants reported reductions of unprotected anal intercourse with HIV-positive partners (p < 0.01); with HIV-negative partners, participants reported fewer insertive and receptive episodes (both p < 0.05). Findings demonstrate that text messaging is a promising intervention for reaching and potentially changing HIV high-risk behaviors among out-of-treatment, methamphetamine-using MSM. PMID:22610370

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

    PubMed

    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. PMID:27039212

  14. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    PubMed

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA. PMID:27182976

  15. Text Messaging Reduces HIV Risk Behaviors among Methamphetamine-using Men Who Have Sex with Men

    PubMed Central

    Reback, Cathy J.; Grant, Deborah Ling; Fletcher, Jesse B.; Branson, Catherine M.; Shoptaw, Steven; Bowers, Jane Rohde; Charania, Mahnaz; Mansergh, Gordon

    2016-01-01

    Text-messaging interventions present a novel approach for targeting high-risk men who have sex with men (MSM) who may not respond to or may be difficult to reach for face-to-face or site-based interventions. Project Tech Support (N = 52) was an open label pilot study testing the feasibility and utility of a text-messaging intervention to reduce methamphetamine use and high-risk sexual behaviors among out-of-treatment MSM. Participants in the two-week intervention received social support and health education text messages transmitted in real-time. At follow-up, there were significant decreases in frequency of methamphetamine use and unprotected sex while on methamphetamine (both p < .01), and a significant increase in self-reported abstinence from methamphetamine use (13.3% vs. 48.9%; p<.001). Additionally, participants reported reductions of unprotected anal intercourse with HIV-positive partners (p < .01); with HIV-negative partners, participants reported fewer insertive and receptive episodes (both p < .05). Findings demonstrate that text messaging is a promising intervention for reaching and potentially changing HIV high-risk behaviors among out-of-treatment, methamphetamine-using MSM. PMID:22610370

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

    PubMed Central

    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. The qualitative methods we used in this study followed the constant comparison process developed by grounded theory methods and analytical ethnography, which is based on familiarity with the social setting and developing propositions while conducting a research study. We used a triangulation of methods and analysis and included qualitative data, such as participant observation notes and in-depth interviews, as well as quantitative data that we collected in drug history matrices. Five themes emerged from the coding of the interview transcripts: (1) sequential polydrug use; (2) concurrent polydrug use (3) temporary substitution of preferred drug; (4) consequential-based use; and (5) switching from using methamphetamine to using prescription drugs. The trajectory patterns of methamphetamine and prescription drug use complicates treatment significantly. PMID:23285312

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

    PubMed Central

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

    2015-01-01

    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”), appears 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 two 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. In Study 1, 11 healthy adult volunteers attended three sessions during which they received methamphetamine (10mg or 20mg) or placebo under double blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin were measured at regular intervals throughout the sessions. In Study 2, 8 healthy adult volunteers attended a single session during which they received one beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither drug increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified. PMID:25853370

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

    PubMed

    Ashizawa, T; Saito, T; Yamamoto, M; Shichinohe, S; Ishikawa, H; Maeda, H; Toki, S; Ozawa, H; Watanabe, M; Takahata, N

    1996-10-01

    We had a case of psychiatric evidence who was homeless and exhibited severe abulia and autism on detention for assault and battery. It was thought that his past history of chronic methamphetamine abuse and his familial history played some part in his showing such symptoms. His mother was alcohol dependent. He was an ACOA (adult child of alcoholics), which might have led to his chronic abuse of methamphetamine. On the other hand, it is well-known fact that the amotivational syndrome induced by marijuana abuse is typified by a diminution of ambition, productivity, and motivation. However, it has been contended that amotivational syndrome is induced not only by marijuana but also by amphetamine and its analogs, cocaine and volatile solvents. Since we positively support this view, we diagnosed the case as amotivational syndrome after long-term methamphetamine abuse. This was also a rare criminal case of amotivational state without hallucinations and delusions after methamphetamine abuse. We suggested that the crime committed in this case was closely related to crime induced by economic problems in residual states of schizophrenic offenders. This could be a case of both ACOA and methamphetamine dependence. There were unresolved alcohol- and drug-related problems in this case. Therefore, careful early intervention in a crisis, cooperation with the authorities and the institutions concerned, and comprehensive rehabilitation should be employed to resolve such alcohol- and drug-related problems. PMID:8940805

  19. Repeated resveratrol treatment attenuates methamphetamine-induced hyperactivity and [3H]dopamine overflow in rodents.

    PubMed

    Miller, Dennis K; Oelrichs, Clark E; Sage, Andrew S; Sun, Grace Y; Simonyi, Agnes

    2013-10-25

    Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been investigated for its potential as a prophylactic against degenerative diseases. It is a sirtulin activator that has recently been shown to regulate dopaminergic systems that contribute to the behavioral effects of methamphetamine and cocaine. The present study examined the impact of resveratrol on stimulant neuropsychopharmacology in rodents. Acute resveratrol treatment (20-40mg/kg) was ineffective to alter methamphetamine (0.5mg/kg)-induced hyperactivity in mice. Rodents received resveratrol once-daily for seven days to determine the effect of repeated polyphenolic treatment. Repeated resveratrol treatment (1-20mg/kg) decreased methamphetamine (0.5mg/kg)-induced hyperactivity in mice. Methamphetamine's (0.1-60μM) efficacy to evoke [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine was also attenuated by repeated resveratrol (1mg/kg) treatment. Repeated resveratrol treatment (10-20mg/kg) did not affect cocaine-induced hyperactivity in mice. Overall, these data suggest that resveratrol appears to have metaplastic and prophylactic activity to minimize the effects of methamphetamine to increase locomotor activity and evoke dopamine release. These data encourage future research to further investigate the relationship between polyphenolics and psychostimulant abuse and dependence. PMID:24012682

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

    PubMed

    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. PMID:24948593

  1. Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects.

    PubMed

    Shanks, Ryan A; Ross, Jordan M; Doyle, Hillary H; Helton, Amanda K; Picou, Brittany N; Schulz, Jordyn; Tavares, Chris; Bryant, Sarah; Dawson, Bryan L; Lloyd, Steven A

    2015-03-15

    The increasing availability, over-prescription, and misuse and abuse of ADHD psychostimulant medications in adolescent populations necessitates studies investigating the long-term effects of these drugs persisting into adulthood. Male and female C57Bl/6J mice were exposed to amphetamine (AMPH) (1.0 and 10 mg/kg), methylphenidate (MPD) (1.0 and 10 mg/kg), or cocaine (COC) (5.0 mg/kg) from postnatal day 22 to 31, which represents an early adolescent period. After an extended period of drug abstinence, adult mice were challenged with a subacute methamphetamine (METH) dose (0.5 mg/kg), to test the long-term effects of adolescent drug exposures on behavioral cross-sensitization using an open field chamber. There were no sex- or dose-specific effects on motor activity in adolescent, saline-treated controls. However, AMPH, MPD, and COC adolescent exposures induced cross-sensitization to a subacute METH dose in adulthood, which is a hallmark of addiction and a marker of long-lasting plastic changes in the brain. Of additional clinical importance, AMPH-exposed male mice demonstrated increased cross-sensitization to METH in contrast to the female-specific response observed in MPD-treated animals. There were no sex-specific effects after adolescent COC exposures. This study demonstrates differential drug, dose, and sex-specific alterations induced by early adolescent psychostimulant exposure, which leads to behavioral alterations that persist into adulthood. PMID:25496784

  2. Increased Drug Use and STI Risk with Injection Drug Use Among HIV-Seronegative Heterosexual Methamphetamine Users†

    PubMed Central

    Cheng, W. Susan; Garfein, Richard S.; Semple, Shirley J.; Strathdee, Steffanie A.; Zians, James K.; Patterson, Thomas L.

    2010-01-01

    Methamphetamine (MA) use has been found to be associated with increased risk of HIV and sexually transmitted infections (STI) among men having sex with men, but it is unknown whether those who inject MA are at greater risk for these infections than those who administer MA by other routes. Furthermore, comparable data from heterosexual MA users are lacking. We investigated whether the HIV and STI risks of male and female heterosexual MA users who inject MA differ from those of comparable users who do not inject. Between 2001 and 2005, we interviewed 452 HIV-negative men and women aged 18 and older who had recently used MA and engaged in unprotected sex. Their mean age was 36.6 years; 68% were male; ethnicity was 49.4% Caucasian, 26.8% African-American, and 12.8% Hispanic. Logistic regression identified factors associated with injecting MA. Compared to non-IDU, IDU were more likely to: be Caucasian; be homeless; have used MA for a longer period and used more grams of MA in the last 30 days; have a history of felony conviction; and report a recent STI. HIV and STI prevention interventions should be tailored according to MA users’ method of administration. PMID:20464802

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

    PubMed Central

    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

  4. Toward a Better Understanding of Non-Addicted, Methamphetamine-Using, Men who Have Sex with Men (MSM) in Atlanta

    PubMed Central

    Dew, Brian J

    2010-01-01

    Methamphetamine use has increasingly become linked with sexual risk behaviors among men have sex with men (MSM). Yet, the majority of research has been done with methamphetamine dependent MSM or with samples in which addiction to the substance was not evaluated. Furthermore, research with methamphetamine-using MSM in the Southern U.S. is lacking. In this study, focus groups and in-depth interviews were conducted in order to understand the motives, context, and other facilitators and barriers of methamphetamine use among non-addicted MSM residing in Atlanta. Participants included 30 non-addicted, methamphetamine-using MSM and 16 local mental and public health officials. Findings from the first of this two-phase formative research project will result in the initial development of a community-tested, culturally-specific social marketing campaign and an individual-based intervention based in HIV-testing facilities. PMID:20657718

  5. Treatment of rats with an anti-(+)-methamphetamine monoclonal antibody shortens the duration of action of repeated (+)-methamphetamine challenges over a one month period

    PubMed Central

    Hambuchen, Michael D.; Rüedi-Bettschen, Daniela; Williams, D. Keith; Hendrickson, Howard; Owens, S. Michael

    2014-01-01

    This study assessed clinical scenarios of continuing monoclonal antibody (mAb) treatment for (+)-methamphetamine (METH) addiction, and the implications of missing or discontinuing this therapy. We hypothesized that chronic anti-METH mAb7F9 (METH KD = 9 nM) treatment of rats could significantly decrease METH-induced behaviors; even with repeated METH challenges, use of METH doses in excess of mAb binding sites, and after discontinuing mAb treatment which results in a 10-fold reduction in mAb7F9 serum concentrations. Male Sprague Dawley rats (n=6/group) were treated with i.v. saline or a loading dose of mAb7F9 to achieve instant steady-state conditions followed by two weekly (141 mg/kg) doses ending on day 14. METH (0.56 mg/kg) was administered four hours and three days after each saline or mAb7F9 treatment, and on day 21. This produced locomotion and rearing behavior that lasted about 120 min in control rats. In mAb7F9 treated rats, METH-induced distance traveled was significantly reduced from 60–120 min (P<0.05) on days 0–21 and rearing was significantly reduced from 60–120 min on days 0–17. METH serum concentrations determined 5 hrs after METH dosing was significantly increased in mAb7F9-treated rats after all METH challenges. On days 24 and 28 (the final day), the rats were administered a 3-fold higher METH dose (1.68 mg/kg). MAb7F9 treated rats showed a substantially earlier termination of the METH-induced locomotion on both days, even though the METH dose exceeded mAb7F9’s binding capacity. METH brain concentrations determined 5 hrs after METH on day 28 were also significantly decreased in mAb7F9-treated rats. In conclusion, over one month, mAb7F9 significantly and continuously bound METH and reduced METH-induced locomotor effects even after discontinuation of mAb treatment and challenge with higher METH doses. PMID:25252196

  6. Methamphetamine induces trace amine-associated receptor 1 (TAAR1) expression in human T lymphocytes: role in immunomodulation.

    PubMed

    Sriram, Uma; Cenna, Jonathan M; Haldar, Bijayesh; Fernandes, Nicole C; Razmpour, Roshanak; Fan, Shongshan; Ramirez, Servio H; Potula, Raghava

    2016-01-01

    The novel transmembrane G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), represents a potential, direct target for drugs of abuse and monoaminergic compounds, including amphetamines. For the first time, our studies have illustrated that there is an induction of TAAR1 mRNA expression in resting T lymphocytes in response to methamphetamine. Methamphetamine treatment for 6 h significantly increased TAAR1 mRNA expression (P < 0.001) and protein expression (P < 0.01) at 24 h. With the use of TAAR1 gene silencing, we demonstrate that methamphetamine-induced cAMP, a classic response to methamphetamine stimulation, is regulated via TAAR1. We also show by TAAR1 knockdown that the down-regulation of IL-2 in T cells by methamphetamine, which we reported earlier, is indeed regulated by TAAR1. Our results also show the presence of TAAR1 in human lymph nodes from HIV-1-infected patients, with or without a history of methamphetamine abuse. TAAR1 expression on lymphocytes was largely in the paracortical lymphoid area of the lymph nodes with enhanced expression in lymph nodes of HIV-1-infected methamphetamine abusers rather than infected-only subjects. In vitro analysis of HIV-1 infection of human PBMCs revealed increased TAAR1 expression in the presence of methamphetamine. In summary, the ability of methamphetamine to activate trace TAAR1 in vitro and to regulate important T cell functions, such as cAMP activation and IL-2 production; the expression of TAAR1 in T lymphocytes in peripheral lymphoid organs, such as lymph nodes; and our in vitro HIV-1 infection model in PBMCs suggests that TAAR1 may play an important role in methamphetamine -mediated immune-modulatory responses. PMID:26302754

  7. Suppression of endogenous PPARγ increases vulnerability to methamphetamine –induced injury in mouse nigrostriatal dopaminergic pathway

    PubMed Central

    Yu, Seong-Jin; Airavaara, Mikko; Shen, Hui; Chou, Jenny; Harvey, Brandon K.; Wang, Yun

    2012-01-01

    Rationale Methamphetamine is a commonly abused drug and dopaminergic neurotoxin. Repeated administration of high doses of methamphetamine induces programmed cell death, suppression of dopamine release, and reduction in locomotor activity. Previous studies have shown that pretreatment with Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist reduced Methamphetamine -induced neurodegeneration. Objectives The purpose of this study was to examine the role of endogenous PPARγ in protecting against methamphetamine toxicity. Methods Adeno-associated virus (AAV) encoding the Cre recombinase gene was unilaterally injected into the left substantia nigra of loxP-PPARγ or control wild type mice. Animals were treated with high doses of methamphetamine 1-month after viral injection. Behavioral tests were examined using Rotarod and rotometer. In vivo voltammetry was used to examine dopamine release/clearance and at 2 months after methamphetamine injection. Results Administration of AAV-Cre selectively removed PPARγ in left nigra in loxP-PPARγ mice but not in the wild type mice. The loxP-PPARγ/AAV-Cre mice that received methamphetamine showed a significant reduction in time on the rotarod and exhibited increased ipislateral rotation using a rotometer. The peak of dopamine release induced by local application of KCl and the rate of dopamine clearance were significantly attenuated in the left striatum of loxP-PPARγ/AAV-Cre animals. Tyrosine hydroxylase immunoreactivity was reduced in the left, compared to right, nigra and dorsal striatum in loxP-PPARγ/AAV-Cre mice receiving high doses of methamphetamine. Conclusion A deficiency in PPARγ increases vulnerability to high doses of methamphetamine. Endogenous PPARγ may play an important role in reducing methamphetamine toxicity in vivo. PMID:22160138

  8. Enacting multiple methamphetamines: the ontological politics of public discourse and consumer accounts of a drug and its effects.

    PubMed

    Dwyer, Robyn; Moore, David

    2013-05-01

    Over the last decade in Australia, methamphetamine has come to be seen as a significant issue for drug research, policy and practice. Concerns have been expressed over its potency, the increasing prevalence of its use and its potential for producing greater levels, and more severe forms, of harm compared to amphetamine or other drugs. In this article, we critically examine some of the ways in which methamphetamine and its effects are produced and reproduced within and through Australian public discourse, focusing in particular on the associations made between methamphetamine and psychosis. We show how public discourse enacts methamphetamine as an anterior, stable, singular and definite object routinely linked to the severe psychological 'harm' of psychosis. We contrast the enactment of methamphetamine within public discourse with how methamphetamine is enacted by consumers of the drug. In their accounts, consumers perform different methamphetamine objects and offer different interpretations of the relationships of these objects to psychological problems and of the ontological nature (i.e. relating to what is real, what is, what exists) of these problems. In examining public discourse and consumer accounts, we challenge conventional ontological understandings of methamphetamine as anterior, singular, stable and definite, and of its psychological effects as indicative of pathology. In line with recent critical social research on drugs, we draw on social studies of science and technology that focus on the performativity of scientific knowledge and material practices. We suggest that recognising the ontological contingency, and therefore the multiplicity, of methamphetamine offers a critical counterpoint to conventional research, policy and practice accounts of methamphetamine and its psychological effects. PMID:23540297

  9. Sex differences in anxiety-like behavior and locomotor activity following prenatal and postnatal methamphetamine exposure in adult rats.

    PubMed

    Hrubá, L; Schutová, B; Šlamberová, R

    2012-01-18

    The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behavior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure. PMID:21884713

  10. Identification of impurities and statistical classification of methamphetamine hydrochloride drugs seized in the China

    PubMed Central

    Zhang, Jian Xin; Zhang, Da Ming; Han, Xu Guang

    2008-01-01

    A total of 48 methamphetamine hydrochloride samples from eight seizures were analyzed using gas chromatography–mass spectrometry (GC–MS) and a flame ionization detector (GC–FID). Major impurities detected include 1,2-dimethyl-3-phenylaziridine, Ephedrine/pseudoephedrine, 1,3-dimethyl-2-phenylnaphthalene, 1-benzyl-3-methylnaphthalene. These data are suggestive of ephedrine/pseudoephedrine as the main precursor of the methamphetamine hydrochloride samples seized during 2006–2007. Additionally the presence of 1,3-dimethyl-2-phenylnaphthalene, 1-benzyl-3-methylnaphthalene is indicative that six seizures were synthesized via the more specific ephedrine/hydriodic acid/red phosphorus method. In addition, five impurities were found for the first time in methamphetamine hydrochloride samples. Seventeen impurity peaks were selected from the GC–FID chromatograms. The peak areas of the selected peaks were then grouped for cluster analysis. PMID:19008060

  11. Examining the relationships between prenatal methamphetamine exposure, early adversity, and child neurobehavioral disinhibition.

    PubMed

    Abar, Beau; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Smith, Lynne M; Arria, Amelia; Huestis, Marilyn; Della Grotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

    2013-09-01

    Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother-infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed. PMID:23067308

  12. Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans.

    PubMed

    Cavallo, Joel S; Mayo, Leah M; de Wit, Harriet

    2016-01-01

    Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported "liking" the MA-paired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies. PMID:27548681

  13. Overlapping Cognitive Patterns in Schizophrenia and Methamphetamine Dependence

    PubMed Central

    Salo, Ruth; Ravizza, Susan; Fassbender, Catherine

    2012-01-01

    Objective To examine whether overlapping cognitive deficits exist in currently drug-abstinent chronic methamphetamine (MA) abusers and schizophrenia (SZ) patients. Background Both SZ and chronic MA abuse are associated with frontostriatal disruption as well as deficits in cognitive control such as selective attention. To identify overlapping cognitive profiles, we compared performance of the two groups on the Stroop attention task. Method Data were analyzed from 69 MA abusers who had been MA-abstinent for differing periods of time and from 23 SZ patients and 38 non-substance-abusing controls. Results The MA abusers in early abstinence displayed more Stroop interference than the SZ patients (p= 0.004), long-term abstinent MA abusers (p= 0.009), and controls (p = 0.002). In the MA abusers, the magnitude of Stroop interference correlated positively with longer drug use [p = 0.01] and negatively with longer drug abstinence [p= 0.04]. No correlations were found between psychotic symptoms and task performance. Conclusions On this task of attentional selection, only the MA abusers in early stages of abstinence showed performance deficits compared to controls. More research is needed to further elucidate overlapping patterns between MA abuse and SZ. PMID:22123586

  14. Methamphetamine administration reduces hippocampal vesicular monoamine transporter-2 uptake.

    PubMed

    Rau, Kristi S; Birdsall, Elisabeth; Volz, Trent J; Riordan, James A; Baucum, Anthony J; Adair, Brian P; Bitter, Rebecca; Gibb, James W; Hanson, Glen R; Fleckenstein, Annette E

    2006-08-01

    Repeated high-dose injections of methamphetamine (METH) rapidly decrease dopamine uptake by the vesicular monoamine transporter-2 (VMAT-2) associated with dopaminergic nerve terminals, as assessed in nonmembrane-associated vesicles purified from striata of treated rats. The purpose of this study was to determine whether METH similarly affects vesicular uptake in the hippocampus; a region innervated by both serotonergic and noradrenergic neurons and profoundly affected by METH treatment. Results revealed that repeated high-dose METH administrations rapidly (within 1 h) reduced hippocampal vesicular dopamine uptake, as assessed in vesicles purified from treated rats. This reduction was likely associated with serotonergic nerve terminals because METH did not further reduce vesicular monoamine uptake in para-chloroamphetamine-lesioned animals. Pretreatment with the serotonin transporter inhibitor fluoxetine blocked both this acute effect on VMAT-2 and the decrease in serotonin content observed 7 days after METH treatment. In contrast, there was no conclusive evidence that METH affected vesicular dopamine uptake in noradrenergic neurons or caused persistent noradrenergic deficits. These findings suggest a link between METH-induced alterations in serotonergic hippocampal vesicular uptake and the persistent hippocampal serotonergic deficits induced by the stimulant. PMID:16687477

  15. Peripheral Ammonia as a Mediator of Methamphetamine Neurotoxicity

    PubMed Central

    Halpin, Laura E.; Yamamoto, Bryan K.

    2012-01-01

    Ammonia is metabolized by the liver and has established neurological effects. The current study examined the possibility that ammonia contributes to the neurotoxic effects of methamphetamine (METH). The results show that a binge dosing regimen of METH to the rat increased plasma and brain ammonia concentrations that were paralleled by evidence of hepatotoxicity. The role of peripheral ammonia in the neurotoxic effects of METH was further substantiated by the demonstration that the enhancement of peripheral ammonia excretion blocked the increases in brain and plasma ammonia and attenuated the long term depletions of dopamine and serotonin typically produced by METH. Conversely, the localized perfusion of ammonia in combination with METH, but not METH alone or ammonia alone, into the striatum recapitulated the neuronal damage produced by the systemic administration of METH. Furthermore, this damage produced by the local administration of ammonia and METH was blocked by the GYKI 52466, an AMPA receptor antagonist. These findings highlight the importance of ammonia derived from the periphery as a small molecule mediator of METH neurotoxicity and more broadly emphasize the importance of peripheral organ damage as a possible mechanism that mediates the neuropathology produced by drugs of abuse and other neuroactive molecules. PMID:22993432

  16. Methamphetamine use among suburban women: Implications for nurse practitioners

    PubMed Central

    Bairan, Annette; Boeri, Miriam; Morian, Janice

    2012-01-01

    Purpose The purpose of this article is to provide nurse practitioners (NPs) with more effective strategies to diagnose methamphetamine (MA) use and assess healthcare needs of MA-using women. Data Sources The researchers collected data from 65 suburban women who were MA users living in the suburbs of a large southeastern city in the US. We conducted in-depth interviews and focus groups examining their life history, drug history, risk behaviors, and access to healthcare. The qualitative findings are examined here. Conclusions Three main themes emerged from the data: 1) gendered stigmatization of MA use; 2) MA related health risk behaviors; and 3) barriers to health and social services, which resulted in a domino effect that led to further life and health complications. When these factors are not effectively addressed, the result is more serious health problems for the women and their children. Implications for Practice This article offers awareness and assessment tools to provide NPs adequate knowledge about the factors associated with MA use in order to treat patients holistically. NPs are strategically positioned to effectively assess, diagnose, treat, and provide linkage to health and social services, especially for suburban females who are a hidden population of drug users. PMID:24510626

  17. Cortical activation during delay discounting in abstinent methamphetamine dependent individuals

    PubMed Central

    Schwartz, Daniel L.; Huckans, Marilyn S.; McFarland, Bentson H.; Meiri, Gal; Stevens, Alexander A.; Mitchell, Suzanne H.

    2010-01-01

    Background Methamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice. Methods We used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls. Results Hard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC. Conclusions Our findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls. PMID:18685833

  18. Enhanced functional connectivity involving the ventromedial hypothalamus following methamphetamine exposure

    PubMed Central

    Zuloaga, Damian G.; Iancu, Ovidiu D.; Weber, Sydney; Etzel, Desiree; Marzulla, Tessa; Stewart, Blair; Allen, Charles N.; Raber, Jacob

    2015-01-01

    Methamphetamine (MA) consumption causes disruption of many biological rhythms including the sleep-wake cycle. This circadian effect is seen shortly following MA exposure and later in life following developmental MA exposure. MA phase shifts, entrains the circadian clock and can also alter the entraining effect of light by currently unknown mechanisms. We analyzed and compared immunoreactivity of the immediate early gene c-Fos, a marker of neuronal activity, to assess neuronal activation 2 h following MA exposure in the light and dark phases. We used network analyses of correlation patterns derived from global brain immunoreactivity patterns of c-Fos, to infer functional connectivity between brain regions. There were five distinct patterns of neuronal activation. In several brain areas, neuronal activation following exposure to MA was stronger in the light than the dark phase, highlighting the importance of considering circadian periods of increased effects of MA in defining experimental conditions and understanding the mechanisms underlying detrimental effects of MA exposure to brain function. Functional connectivity between the ventromedial hypothalamus (VMH) and other brain areas, including the paraventricular nucleus of the hypothalamus and basolateral and medial amygdala, was enhanced following MA exposure, suggesting a role for the VMH in the effects of MA on the brain. PMID:26441501

  19. Acute and chronic environmental effects of clandestine methamphetamine waste.

    PubMed

    Kates, Lisa N; Knapp, Charles W; Keenan, Helen E

    2014-09-15

    The illicit manufacture of methamphetamine (MAP) produces substantial amounts of hazardous waste that is dumped illegally. This study presents the first environmental evaluation of waste produced from illicit MAP manufacture. Chemical oxygen demand (COD) was measured to assess immediate oxygen depletion effects. A mixture of five waste components (10mg/L/chemical) was found to have a COD (130 mg/L) higher than the European Union wastewater discharge regulations (125 mg/L). Two environmental partition coefficients, K(OW) and K(OC), were measured for several chemicals identified in MAP waste. Experimental values were input into a computer fugacity model (EPI Suite™) to estimate environmental fate. Experimental log K(OW) values ranged from -0.98 to 4.91, which were in accordance with computer estimated values. Experimental K(OC) values ranged from 11 to 72, which were much lower than the default computer values. The experimental fugacity model for discharge to water estimates that waste components will remain in the water compartment for 15 to 37 days. Using a combination of laboratory experimentation and computer modelling, the environmental fate of MAP waste products was estimated. While fugacity models using experimental and computational values were very similar, default computer models should not take the place of laboratory experimentation. PMID:25000573

  20. Glial Reactivity in Resistance to Methamphetamine-Induced Neurotoxicity

    PubMed Central

    Friend, Danielle M.; Keefe, Kristen A.

    2013-01-01

    Neurotoxic regimens of methamphetamine (METH) result in reactive microglia and astrocytes in striatum. Prior data indicate that rats with partial dopamine (DA) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re-exposed to METH 30 days later. Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH-induced neurotoxicity. To date, the astrocyte response in such resistance has not been examined. Thus, this study examined glial-fibrillary acidic protein (GFAP) and CD11b protein expression in striata of animals administered saline or a neurotoxic regimen of METH on postnatal days 60 and/or 90 (Saline:Saline, Saline:METH, METH:Saline, METH:METH). Consistent with previous work, animals experiencing acute toxicity (Saline:METH) showed both activated microglia and astocytes, whereas those resistant to the acute toxicity (METH:METH) did not show activated microglia. Interestingly, GFAP expression remained elevated in rats exposed to METH at PND60 (METH:Saline), and was not elevated further in resistant rats treated for the second time with METH (METH:METH). These data suggest that astrocytes remain reactive up to 30 days post-METH exposure. Additionally, these data indicate that astrocyte reactivity does not reflect acute, METH-induced DA terminal toxicity, whereas microglial reactivity does. PMID:23414433

  1. Differences between Ecstasy-using and nonusing methamphetamine users.

    PubMed

    Brecht, Mary-Lynn; von Mayrhauser, Christina

    2002-01-01

    There have been recent alarming increases in Ecstasy use and growing evidence of possible long-term neurological and cognitive effects. This article considers Ecstasy use within its common polydrug context (specifically with methamphetamine [MA]), examining differences between Ecstasy-using and nonusing subgroups of clients treated for MA use, and exploring the relationship of Ecstasy use to selected treatment outcomes. Multivariate logistic regression showed Ecstasy+MA users differing from MA users who have not used Ecstasy primarily in terms of sociodemographics (higher income, fewer children), substance abuse behaviors and motivators (lifetime history of more types of drugs, more likely to report use of Ecstasy to enhance sex, more drug-related problems), lifestyle (more likely to have had same-sex sex partners), and treatment characteristics (younger at admission, less likely to complete treatment). A lower rate of treatment completion was predicted by Ecstasy use, even when controlling for other Ecstasy-related characteristics; however, time to relapse was not significantly related to Ecstasy use. These results distinguishing subgroups of stimulant users may help guide additional research into specific behavioral causes and correlates of Ecstasy use, which could in turn guide specialization of promising MA-related treatment approaches for Ecstasy users. PMID:12691212

  2. Role of PUMA in methamphetamine-induced neuronal apoptosis.

    PubMed

    Chen, Chuanxiang; Qincao, Litao; Xu, Jingtao; Du, Sihao; Huang, Enping; Liu, Chao; Lin, Zhoumeng; Xie, Wei-Bing; Wang, Huijun

    2016-01-01

    Exposure to methamphetamine (METH), a widely used illicit drug, has been shown to cause neuron apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a key mediator in neuronal apoptosis. This study aimed to examine the effects of PUMA in METH-induced neuronal apoptosis. We determined PUMA protein expression in PC12 cells and SH-SY5Y cells after METH exposure using western blot. We also observed the effect of METH on neuronal apoptosis after silencing PUMA expression with siRNA using TUNEL staining and flow cytometry. Additionally, to investigate possible mechanisms of METH-induced PUMA-mediated neuronal apoptosis, we measured the protein expression of apoptotic markers, including cleaved caspase-3, cleaved PARP, Bax, B-cell leukemia/lymphoma-2 (Bcl-2) and cytochrome c (cyto c), after METH treatment with or without PUMA knockdown. Results showed that METH exposure induced cell apoptosis, increased PUMA protein levels, activated caspase-3 and PARP, elevated Bax and reduced Bcl-2 expression, as well as increased the release of cyto c from mitochondria to the cytoplasm in both PC12 and SH-SY5Y cells. All these effects were attenuated or reversed after silencing PUMA. A schematic depicting the role of PUMA in METH-induced mitochondrial apoptotic pathway was proposed. Our results suggest that PUMA plays an important role in METH-triggered apoptosis and it may be a potential target for ameliorating neuronal injury and apoptosis caused by METH. PMID:26524635

  3. Elements concentrations in the scalp hair of methamphetamine abusers.

    PubMed

    Luo, Ruxin; Zhang, Sujing; Xiang, Ping; Shen, Baohua; Zhuo, Xianyi; Ma, Dong

    2015-04-01

    The concentrations of 16 elements (As, Au, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Se, Sr and Zn) in the hair of 40 methamphetamine (METH) abusers and control subjects were determined by inductively coupled plasma mass spectrometry (ICP-MS). Comparisons of the element levels in the hair of properly matched METH abuser and control groups revealed significant imbalances in the concentrations of 6 elements (As, Au, Ca, Cu, Mg and Sr) between the abuser and control groups. Ca (p<0.01), Cu (p<0.05), Mg (p<0.01) and Sr (p<0.01) levels are significantly lower in the hair samples of METH abusers compared to control subjects, whereas the As (p<0.01) and Au (p<0.01) concentrations are higher. The concentration of the remaining elements in the hair of METH abusers was similar to the concentration in the control subjects. The geometric means for each element in hair of METH abuser and control subjects are presented. The cause of these alterations is also discussed. PMID:25682498

  4. Quality of life among treatment seeking methamphetamine-dependent individuals.

    PubMed

    Gonzales, Rachel; Ang, Alfonso; Glik, Deborah C; Rawson, Richard A; Lee, Stella; Iguchi, Martin Y

    2011-01-01

    As the number of men and women entering treatment for substance use disorders continues to increase across the country, it becomes vitally important to understand their quality of life (QOL) or perceived health status, in order to inform treatment efforts for improving such outcomes. To date, QOL assessments among methamphetamine (MA) dependent users are limited. This paper examines QOL health status among a sample of 838 treatment seeking MA users at admission. Using regression analysis, predictors of QOL are examined among MA users. Predictors of poor QOL among MA users at treatment admission included being female, white, high school educated or more, married, experiencing psychosocial dysfunction (lifetime trauma, suicide, social conflict), reporting a high frequency of both MA and polydrugs for 15 days or more in the past month, chronicity of MA and polydrug use, injection use, and having co-morbid medical and psychiatric impairment. Employment status was the only factor related to better health status perceptions. This study expands the scope of scholarly examination of MA-dependent users entering treatment, as there has not been a development of coherent profiles of QOL among representative samples of clinical MA-abusing populations to date. PMID:21679268

  5. Effect of Methamphetamine Dependence on Heart Rate Variability

    PubMed Central

    Henry, Brook L.; Minassian, Arpi; Perry, William

    2010-01-01

    Background Methamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology, and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication, but has not been characterized in METH use. We recorded HRV in a sample of currently abstinent individuals with a history of METH dependence compared to age- and gender-matched drug-free comparison subjects. Method HRV was assessed using time domain, frequency domain, and nonlinear entropic analyses in 17 previously METH-dependent and 21 drug-free comparison individuals during a 5 minute rest period. Results The METH-dependent group demonstrated significant reduction in HRV, reduced parasympathetic activity, and diminished heartbeat complexity relative to comparison participants. More recent METH use was associated with increased sympathetic tone. Conclusion Chronic METH exposure may be associated with decreased HRV, impaired vagal function, and reduction in heart rate complexity as assessed by multiple methods of analysis. We discuss and review evidence that impaired HRV may be related to the cardiotoxic or neurotoxic effects of prolonged METH use. PMID:21182570

  6. Condoms - male

    MedlinePlus

    ... Rubbers; Male condoms; Contraceptive - condom; Contraception - condom; Barrier method - condom ... infections.) Latex rubber Polyurethane Condoms are the only method of birth control for men that are not ...

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

    PubMed

    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. PMID:26334786

  8. The effects of vasopressin and oxytocin on methamphetamine-induced place preference behaviour in rats.

    PubMed

    Subiah, Cassandra O; Mabandla, Musa V; Phulukdaree, Alisa; Chuturgoon, Anil A; Daniels, Willie M U

    2012-09-01

    Methamphetamine is a highly addictive stimulant drug whose illicit use and resultant addiction has become an alarming global phenomenon. The mesolimbic dopaminergic pathway has been shown to be fundamental to the establishment of addictive behaviour. This pathway, as part of the reward system of the brain, has also been shown to be important in classical conditioning, which is a learnt response. Within the modulation of learning and memory, the neurohypophyseal hormones vasopressin and oxytocin have been reported to play a vital role, with vasopressin exerting a long- term facilitatory effect and oxytocin exerting an inhibitory effect. Therefore we adopted a conditioned place preference model to investigate whether vasopressin V1b receptor antagonist SSR 149415 or oxytocin treatment would cause a decrease in the seeking behaviour in a reinstatement paradigm. Behavioural findings indicated that methamphetamine induced a change in the place preference in the majority of our animals. This change in place preference was not seen when vasopressin was administered during the extinction phase. On the other hand the methamphetamine-induced change in place preference was enhanced during the reinstatement phase in the animals that were treated with oxytocin. Striatal dopamine levels were determined, as methamphetamine is known to increase dopamine transmission in this area. Significant changes in dopamine levels were observed in some of our animals. Rats that received both methamphetamine and oxytocin had significantly higher striatal dopamine than those that received oxytocin alone. Western blot analysis for hippocampal cyclic AMP response element binding protein (CREB) was also conducted as a possible indicator of glutamatergic NMDA receptor activity, a pathway that is important for learning and memory. The Western blot analysis showed no changes in hippocampal pCREB expression. Overall our data led us to conclude that methamphetamine treatment can change place preference

  9. Effects of Methamphetamine Administration on Information Gathering during Probabilistic Reasoning in Healthy Humans

    PubMed Central

    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. PMID:25061949

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

    PubMed

    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

  11. “Tweaking and Geeking, Just Having Some Fun”: An Analysis of Methamphetamine Poems

    PubMed Central

    Sexton, Rocky L.; Carlson, Robert G.; Leukefeld, Carl G.; Booth, Brenda M.

    2013-01-01

    There is a body of methamphetamine-themed poetry that speaks regretfully of the highly negative experiences of those in recovery from methamphetamine (MA) addiction or who feel trapped in an MA-using lifestyle. During ethnographic research in western Kentucky, the author collected two MA-themed poems from active MA users that differ from other MA poetry. They describe misadventures that occur during MA “binges.” However, the text and tone of the poems are comically ironic and represent optimism rather than regret toward MA use. Analyzing these poems provide valuable insights into local patterns of MA use, related terminology, and attitudes toward MA use. PMID:21053760

  12. Development of an automated data processing method for sample to sample comparison of seized methamphetamines.

    PubMed

    Choe, Sanggil; Lee, Jaesin; Choi, Hyeyoung; Park, Yujin; Lee, Heesang; Pyo, Jaesung; Jo, Jiyeong; Park, Yonghoon; Choi, Hwakyung; Kim, Suncheun

    2012-11-30

    The information about the sources of supply, trafficking routes, distribution patterns and conspiracy links can be obtained from methamphetamine profiling. The precursor and synthetic method for the clandestine manufacture can be estimated from the analysis of minor impurities contained in methamphetamine. Also, the similarity between samples can be evaluated using the peaks that appear in chromatograms. In South Korea, methamphetamine was the most popular drug but the total seized amount of methamphetamine whole through the country was very small. Therefore, it would be more important to find the links between samples than the other uses of methamphetamine profiling. Many Asian countries including Japan and South Korea have been using the method developed by National Research Institute of Police Science of Japan. The method used gas chromatography-flame ionization detector (GC-FID), DB-5 column and four internal standards. It was developed to increase the amount of impurities and minimize the amount of methamphetamine. After GC-FID analysis, the raw data have to be processed. The data processing steps are very complex and require a lot of time and effort. In this study, Microsoft Visual Basic Application (VBA) modules were developed to handle these data processing steps. This module collected the results from the data into an Excel file and then corrected the retention time shift and response deviation generated from the sample preparation and instruments analysis. The developed modules were tested for their performance using 10 samples from 5 different cases. The processed results were analyzed with Pearson correlation coefficient for similarity assessment and the correlation coefficient of the two samples from the same case was more than 0.99. When the modules were applied to 131 seized methamphetamine samples, four samples from two different cases were found to have the common origin and the chromatograms of the four samples were appeared visually identical

  13. Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor based brain morphometry and discriminant analysis

    PubMed Central

    Sowell, Elizabeth R.; Leow, Alex D.; Bookheimer, Susan Y.; Smith, Lynne M.; O’Connor, Mary J.; Kan, Eric; Rosso, Carly; Houston, Suzanne; Dinov, Ivo D.; Thompson, Paul M.

    2010-01-01

    Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5 to 15), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls (CON group). Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally, and right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and within the MAA group, a negative correlation between full-scale IQ (FSIQ) scores and caudate volume was observed. Limbic structures including the anterior and posterior cingulate, the inferior frontal gyrus (IFG) and ventral and lateral temporal lobes bilaterally were increased in volume in both exposure groups. Further, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure, and that more severe striatal damage is associated with more severe cognitive deficit. PMID:20237258

  14. Sex, Drugs (Methamphetamines), and the Internet: Increasing Syphilis Among Men Who Have Sex With Men in California, 2004–2008

    PubMed Central

    Samuel, Michael C.; Lo, Terrence; Bernstein, Kyle T.; Aynalem, Getahun; Klausner, Jeffrey D.; Bolan, Gail

    2013-01-01

    Objectives. We examined primary and secondary syphilis cases among men who have sex with men (MSM) in California, and the association of methamphetamine use and Internet use to meet sex partners (Internet use) with number of sex partners. Methods. We analyzed California surveillance data for MSM who were diagnosed with syphilis between 2004 and 2008, to assess differences in the mean number of sex partners by methamphetamine use and mutually exclusive groups of patients reporting Internet use (Internet users). Results. Large proportions of patients reported methamphetamine use (19.2%) and Internet use (36.4%). From 2006 through 2008, Adam4Adam was the most frequently reported Web site statewide, despite temporal and regional differences in Web site usage. Methamphetamine users reported more sex partners (mean = 11.7) than nonmethamphetamine users (mean = 5.6; P < .001). Internet users reported more sex partners (mean = 9.8) than non-Internet users (mean = 5.0; P < .001). Multivariable analysis of variance confirmed an independent association of methamphetamine and Internet use with increased numbers of sex partners. Conclusions. Higher numbers of partners among MSM syphilis patients were associated with methamphetamine and Internet use. Collaboration between currently stand-alone interventions targeting methamphetamine users and Internet users may offer potential advances in sexually transmitted disease control efforts. PMID:23153138

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

    PubMed

    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. PMID:25582886

  16. Gray-Matter Volume, Midbrain Dopamine D2/D3 Receptors and Drug Craving in Methamphetamine Users

    PubMed Central

    Morales, Angelica A.; Kohno, Milky; Robertson, Chelsea L.; Dean, Andy C.; Mandelkern, Mark A.; London, Edythe D.

    2015-01-01

    Dysfunction of the mesocorticolimbic system plays a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [18F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, p<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum, and thalamus (p<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance use disorders. PMID:25896164

  17. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

    PubMed

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Ellis, Jonathan D; Walters, Elliot T; Stout, Kristen A; McIntosh, J Michael; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2015-12-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection. PMID:26391161

  18. HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

    PubMed Central

    Borgmann, Kathleen; Ghorpade, Anuja

    2015-01-01

    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 and 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 impedes adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression toward AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte numbers and activity, cytokine signaling, phagocytic function and infiltration through the blood brain barrier. Further, METH triggers the dopamine reward pathway and leads to impaired neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation, which modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress, and excitotoxicity. Pathologically, reactive gliosis 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, this review highlights alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, with special emphasis on HAND-associated neuroinflammation. Importantly, this review carefully evaluates interventions targeting astrocytes in HAND and METH as potential novel therapeutic approaches. This comprehensive overview indicates, without a doubt, that during HIV-1 infection and METH abuse, a complex dialog between all neural cells is orchestrated through astrocyte regulated neuroinflammation. PMID:26579077

  19. Methamphetamine effects on blood-brain barrier structure and function

    PubMed Central

    Northrop, Nicole A.; Yamamoto, Bryan K.

    2015-01-01

    Methamphetamine (Meth) is a widely abuse psychostimulant. Traditionally, studies have focused on the neurotoxic effects of Meth on monoaminergic neurotransmitter terminals. Recently, both in vitro and in vivo studies have investigated the effects of Meth on the BBB and found that Meth produces a decrease in BBB structural proteins and an increase in BBB permeability to various molecules. Moreover, preclinical studies are validated by clinical studies in which human Meth users have increased concentrations of toxins in the brain. Therefore, this review will focus on the structural and functional disruption of the BBB caused by Meth and the mechanisms that contribute to Meth-induced BBB disruption. The review will reveal that the mechanisms by which Meth damages dopamine and serotonin terminals are similar to the mechanisms by which the blood-brain barrier (BBB) is damaged. Furthermore, this review will cover the factors that are known to potentiate the effects of Meth (McCann et al., 1998) on the BBB, such as stress and HIV, both of which are co-morbid conditions associated with Meth abuse. Overall, the goal of this review is to demonstrate that the scope of damage produced by Meth goes beyond damage to monoaminergic neurotransmitter systems to include BBB disruption as well as provide a rationale for investigating therapeutics to treat Meth-induced BBB disruption. Since a breach of the BBB can have a multitude of consequences, therapies directed toward the treatment of BBB disruption may help to ameliorate the long-term neurodegeneration and cognitive deficits produced by Meth and possibly even Meth addiction. PMID:25788874

  20. Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans

    PubMed Central

    Mayo, Leah M.; de Wit, Harriet

    2016-01-01

    Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported “liking” the MA-paired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies. PMID:27548681

  1. A VACCINE AGAINST METHAMPHETAMINE ATTENUATES ITS BEHAVIORAL EFFECTS IN MICE

    PubMed Central

    Shen, Xiaoyun Y.; Kosten, Therese A.; Lopez, Angel Y.; Kinsey, Berma M.; Kosten, Thomas R.; Orson, Frank M.

    2012-01-01

    BACKGROUND Vaccines have treatment potential for methamphetamine (MA) addiction. We tested whether a conjugate vaccine against MA (succinyl-methamphetamine–keyhole limpet hemocyanin carrier protein; SMA-KLH) would generate MA antibodies and alter MA-induced behaviors. METHODS Mice were injected with SMA-KLH and received booster administrations 3-and 20-weeks later. Serum antibody titers reached peak levels by 4–6 weeks, remained at a modest level through 18-weeks, peaked again at 22-wks after the second boost, and were still elevated at 35-weeks. At 7 weeks, groups of vaccinated and non-vaccinated mice were administered one of three MA doses (1, 2, or 3 mg/kg) to assess locomotor activity. RESULTS Non-vaccinated mice showed dose-dependent effects of MA with hypolocomotion at the lowest dose and elevated activity levels at the highest dose. Both dose effects were reduced in SMA-KLH groups, particularly low dose-induced hypolocomotion at later times post MA administration. Separate groups of vaccinated and non-vaccinated mice were trained in MA place conditioning at 30-weeks with either 0 (vehicle) or 0.5 mg/kg MA. Although times spent in the MA-paired side did not differ between groups on Test vs. Baseline sessions, SMA-KLH mice conditioned with MA showed reduced conditioned approach behaviors and decreased conditioned activity levels compared to control groups. CONCLUSION These data suggest SMA-KLH attenuates the ability of MA to support place conditioning and reduces or delays its locomotor effects. Overall, results support SMA-KLH as a candidate MA vaccine. PMID:23022610

  2. Effects of Sodium Butyrate on Methamphetamine-Sensitized Locomotor Activity

    PubMed Central

    Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.

    2012-01-01

    Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2 mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, appeared to increase striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior. PMID:23137698

  3. Pharmacological effects of two anti-methamphetamine monoclonal antibodies

    PubMed Central

    Laurenzana, Elizabeth M; Stevens, Misty W; Frank, John C; Hambuchen, Michael D; Hendrickson, Howard P; White, Sarah J; Williams, D Keith; Owens, S Michael; Gentry, W Brooks

    2014-01-01

    This lead candidate selection study compared two anti-(+)-methamphetamine (METH) monoclonal antibodies (mAb) to determine their ability to reduce METH-induced locomotor effects and redistribute METH and (+)-amphetamine (AMP) in a preclinical overdose model. Both mAbs have high affinity for METH, but mAb4G9 has moderate and mAb7F9 has low affinity for AMP. In the placebo-controlled behavioral experiment, the effects of each mAb on the locomotor response to a single 1 mg/kg intravenous (IV) METH dose were determined in rats. The doses of mAb binding sites were administered such that they equaled 1, 0.56, 0.32, and 0.1 times the molar equivalent (mol-eq) of METH in the body 30 min after the METH dose. METH disposition was determined in separate animals that similarly received either a 1 or 0.32 mol-eq dose of mAb binding sites 30 min after a 1 mg/kg METH dose. Total METH-induced distance traveled was significantly reduced in rats that received the highest three doses of each mAb compared with saline. The duration of METH effects was also significantly reduced by mAb7F9 at the highest dose. The disposition of METH was altered dose-dependently by both mAbs as shown in reductions of volume of distribution and total clearance, and increases in elimination half-life. These data indicate that both mAbs are effective at reducing METH-induced behavior and favorably altering METH disposition. Both were therefore suitable for further preclinical testing as potential human medications for treating METH use; however, due to results reported here and in later studies, mAb7F9 was selected for clinical development. PMID:25483484

  4. Influence of Betaxolol on the Methamphetamine Dependence in Mice

    PubMed Central

    Kim, Byoung-Jo; Park, Jong-Il; Eun, Hun-Jeong

    2016-01-01

    Objective The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. Methods The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. Results The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. Conclusion These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP. PMID:27247598

  5. Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

    PubMed Central

    Lominac, Kevin D.; McKenna, Courtney L.; Schwartz, Lisa M.; Ruiz, Paige N.; Wroten, Melissa G.; Miller, Bailey W.; Holloway, John J.; Travis, Katherine O.; Rajasekar, Ganesh; Maliniak, Dan; Thompson, Andrew B.; Urman, Lawrence E.; Phillips, Tamara J.; Szumlinski, Karen K.

    2014-01-01

    Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5–10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction. PMID:24847220

  6. Ammonia Mediates Methamphetamine-Induced Increases in Glutamate and Excitotoxicity

    PubMed Central

    Halpin, Laura E; Northrop, Nicole A; Yamamoto, Bryan K

    2014-01-01

    Ammonia has been identified to have a significant role in the long-term damage to dopamine and serotonin terminals produced by methamphetamine (METH), but how ammonia contributes to this damage is unknown. Experiments were conducted to identify whether increases in brain ammonia affect METH-induced increases in glutamate and subsequent excitotoxicity. Increases in striatal glutamate were measured using in vivo microdialysis. To examine the role of ammonia in mediating changes in extracellular glutamate after METH exposure, lactulose was used to decrease plasma and brain ammonia. Lactulose is a non-absorbable disaccharide, which alters the intestinal lumen through multiple mechanisms that lead to the increased peripheral excretion of ammonia. METH caused a significant increase in extracellular glutamate that was prevented by lactulose. Lactulose had no effect on METH-induced hyperthermia. To determine if ammonia contributed to excitotoxicity, the effect of METH and lactulose treatment on calpain-mediated spectrin proteolysis was measured. METH significantly increased calpain-specific spectrin breakdown products, and this increase was prevented with lactulose treatment. To examine if ammonia-induced increases in extracellular glutamate were mediated by excitatory amino-acid transporters, the reverse dialysis of ammonia, the glutamate transporter inhibitor, DL-threo-β-benzyloxyaspartic acid (TBOA), or the combination of the two directly into the striatum of awake, freely moving rats was conducted. TBOA blocked the increases in extracellular glutamate produced by the reverse dialysis of ammonia. These findings demonstrate that ammonia mediates METH-induced increases in extracellular glutamate through an excitatory amino-acid transporter to cause excitotoxicity. PMID:24165886

  7. Adenosine 2A receptors modulate reward behaviours for methamphetamine.

    PubMed

    Chesworth, Rose; Brown, Robyn M; Kim, Jee Hyun; Ledent, Catherine; Lawrence, Andrew J

    2016-03-01

    Addiction to methamphetamine (METH) is a global health problem for which there are no approved pharmacotherapies. The adenosine 2A (A2 A ) receptor presents a potential therapeutic target for METH abuse due to its modulatory effects on striatal dopamine and glutamate transmission. Notably, A2 A receptor signalling has been implicated in the rewarding effects of alcohol, cocaine and opiates; yet, the role of this receptor in METH consumption and seeking is essentially unknown. Therefore, the current study used A2 A knockout (KO) mice to assess the role of A2 A in behaviours relevant to METH addiction. METH conditioned place preference was absent in A2 A KO mice compared with wild-type (WT) littermates. Repeated METH treatment produced locomotor sensitization in both genotypes; however, sensitization was attenuated in A2 A KO mice in a dose-related manner. METH intravenous self-administration was intact in A2 A KO mice over a range of doses and schedules of reinforcement. However, the motivation to self-administer was reduced in A2 A KO mice. Regression analysis further supported the observation that the motivation to self-administer METH was reduced in A2 A KO mice even when self-administration was similar to WT mice. Sucrose self-administration was also reduced in A2 A KO mice but only at higher schedules of reinforcement. Collectively, these data suggest that A2 A signalling is critically required to integrate rewarding and motivational properties of both METH and natural rewards. PMID:25612195

  8. Decreased dopamine activity predicts relapse in methamphetamine abusers

    SciTech Connect

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  9. Prefrontal glutamate correlates of methamphetamine sensitization and preference.

    PubMed

    Lominac, Kevin D; Quadir, Sema G; Barrett, Hannah M; McKenna, Courtney L; Schwartz, Lisa M; Ruiz, Paige N; Wroten, Melissa G; Campbell, Rianne R; Miller, Bailey W; Holloway, John J; Travis, Katherine O; Rajasekar, Ganesh; Maliniak, Dan; Thompson, Andrew B; Urman, Lawrence E; Kippin, Tod E; Phillips, Tamara J; Szumlinski, Karen K

    2016-03-01

    Methamphetamine (MA) is a widely misused, highly addictive psychostimulant that elicits pronounced deficits in neurocognitive function related to hypo-functioning of the prefrontal cortex (PFC). Our understanding of how repeated MA impacts excitatory glutamatergic transmission within the PFC is limited, as is information about the relationship between PFC glutamate and addiction vulnerability/resiliency. In vivo microdialysis and immunoblotting studies characterized the effects of MA (ten injections of 2 mg/kg, i.p.) upon extracellular glutamate in C57BL/6J mice and upon glutamate receptor and transporter expression, within the medial PFC. Glutamatergic correlates of both genetic and idiopathic variance in MA preference/intake were determined through studies of high vs. low MA-drinking selectively bred mouse lines (MAHDR vs. MALDR, respectively) and inbred C57BL/6J mice exhibiting spontaneously divergent place-conditioning phenotypes. Repeated MA sensitized drug-induced glutamate release and lowered indices of N-methyl-d-aspartate receptor expression in C57BL/6J mice, but did not alter basal extracellular glutamate content or total protein expression of Homer proteins, or metabotropic or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors. Elevated basal glutamate, blunted MA-induced glutamate release and ERK activation, as well as reduced protein expression of mGlu2/3 and Homer2a/b were all correlated biochemical traits of selection for high vs. low MA drinking, and Homer2a/b levels were inversely correlated with the motivational valence of MA in C57BL/6J mice. These data provide novel evidence that repeated, low-dose MA is sufficient to perturb pre- and post-synaptic aspects of glutamate transmission within the medial PFC and that glutamate anomalies within this region may contribute to both genetic and idiopathic variance in MA addiction vulnerability/resiliency. PMID:26742098

  10. The Persian methamphetamine use in methadone treatment in Iran: implication for prevention and treatment in an upper-middle income country.

    PubMed

    Alam-Mehrjerdi, Zahra; Abdollahi, Mohammad

    2015-01-01

    As the most populated Persian Gulf country in West Asia, methamphetamine use in methadone maintenance treatment (MMT) is a new health concern in Iran. Methamphetamine use in MMT can originate in methadone misconceptions or the stimulant effects of methamphetamine use. Several research studies have highlighted the prevalence of methamphetamine use in Iran and conducting further studies on this issue is being developed. Opiate use is treated with MMT. But, there is no effective pharmacological treatment for methamphetamine use and cognitive-behavioral interventions have still remained the best practice. As a psychostimulant drug, methamphetamine use can lead to poor treatment outcomes or even treatment failure among patients in MMT. Therefore, the implementation of methamphetamine education and prevention programs in MMT is required. Prescribing adequate methadone dose and the treatment of comorbidities as well as, doing a series of activities outside treatment is underscored. Methamphetamine use has a chronic nature and methamphetamine treatment is a long-term procedure with a high rate of relapse. Therefore, the implementation of long-term motivational interviewing, teaching necessary skills to prevent relapse and case management is highlighted. A long-term collaboration between treatment teams, patients and their families is suggested to manage methamphetamine use in MMT. PMID:26578071

  11. Condoms - male

    MedlinePlus

    ... PREGNANCY? If the sperm contained in a male's semen reach a woman's vagina, pregnancy may occur. Condoms ... receptacle) on the end of it (to collect semen), place the condom against the top of the ...

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

    ERIC Educational Resources Information Center

    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.

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

    PubMed

    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. PMID:25479528

  14. Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals.

    PubMed

    Salo, Ruth; Nordahl, Thomas E; Possin, Kate; Leamon, Martin; Gibson, David R; Galloway, Gantt P; Flynn, Neil M; Henik, Avishai; Pfefferbaum, Adolf; Sullivan, Edith V

    2002-08-01

    Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others. PMID:12140121

  15. Characterization of route specific impurities found in methamphetamine synthesized by the Leuckart and reductive amination methods.

    PubMed

    Kunalan, Vanitha; Nic Daéid, Niamh; Kerr, William J; Buchanan, Hilary A S; McPherson, Allan R

    2009-09-01

    Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of "route specific" impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the "target impurities" recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes. PMID:19637924

  16. Perceived Child Behavior Problems, Parenting Stress, and Maternal Depressive Symptoms among Prenatal Methamphetamine Users

    ERIC Educational Resources Information Center

    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.…

  17. An Investigation of Bioecological Influences Associated with First Use of Methamphetamine in a Rural State

    ERIC Educational Resources Information Center

    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…

  18. Methamphetamine Users in a Community-Based Drug Court: Does Gender Matter?

    ERIC Educational Resources Information Center

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

    2007-01-01

    This paper examines men and women methamphetamine (meth) users who participated in a community-based drug court. The treatment of female drug users is a particularly salient issue because of the concerns with relapse and recidivism. For the current study, we studied the impact of the drug court by gender on a group of high-risk/high-need meth…

  19. A Vodcasted, Cross-Disciplinary, Behavioral Neuroscience Laboratory Exercise Investigating the Effects of Methamphetamine on Aggression

    ERIC Educational Resources Information Center

    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…

  20. Characterization of Route Specific Impurities Found in Methamphetamine Synthesized by the Leuckart and Reductive Amination Methods

    PubMed Central

    2009-01-01

    Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of “route specific” impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the “target impurities” recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes. PMID:19637924

  1. The Impact of Distinct Chemical Structures for the Development of a Methamphetamine Vaccine

    PubMed Central

    Moreno, Amira Y.; Mayorov, Alexander V.; Janda, Kim D.

    2011-01-01

    (+)-Methamphetamine (METH) use and addiction has grown at alarming rates over the past two decades, while no approved pharmacotherapy exists for its treatment. Immunopharmacotherapy has the potential to offer relief through producing highly specific antibodies that prevent drug penetration across the blood-brain barrier thus decreasing reinforcement of the behavior. Current immunotherapy efforts against methamphetamine have focused on a single hapten structure, namely linker attachment at the aromatic ring of the METH molecule. Hapten design is largely responsible for immune recognition as it affects presentation of the target antigen and thus the quality of the response. In the current paper we report the systematic generation of a series of haptens designed to target the most stable conformations of methamphetamine as determined by molecular modeling. Based on our previous studies with nicotine, we show that introduction of strategic molecular constrain is able to maximize immune recognition of the target structure as evidenced by higher antibody affinity. Vaccination of GIX+ mice with six unique METH immunoconjugates, resulted in high antibody titers for three particularly promising formulations (45–108 μg/mL, after second immunization) and high affinity (82, 130 and 169 nM for MH2, MH6 and MH7 hapten-based vaccines, respectively). These findings represent a unique approach to the design of new vaccines against methamphetamine abuse. PMID:21473576

  2. Methamphetamine Exposure, Iron Deficiency, and Implications for Cognitive-Communicative Function: A Case Study

    ERIC Educational Resources Information Center

    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…

  3. Personality Characteristics of Adolescents with Hallucinogen, Methamphetamine, and Cannabis Dependence: A Comparative Study

    ERIC Educational Resources Information Center

    Palmer, Glen A.; Daiss, Doyle D.

    2005-01-01

    A comparison of personality factors on scales of the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) was conducted with a sample of adolescents referred to a residential substance abuse treatment program. A total of sixty adolescents identified with hallucinogen (n = 20), cannabis (n = 20), or methamphetamine (n = 20) as their drug…

  4. Distributed Attentional Deficits in Chronic Methamphetamine Abusers: Evidence from the Attentional Network Task (ANT)

    ERIC Educational Resources Information Center

    Salo, Ruth; Gabay, Shai; Fassbender, Catherine; Henik, Avishai

    2011-01-01

    Objective: The goal of the present study was to examine distributed attentional functions in long-term but currently abstinent methamphetamine (MA) abusers using a task that measures attentional alertness, orienting, and conflict resolution. Methods: Thirty currently abstinent MA abusers (1 month-5 years) and 22 healthy non-substance using adults…

  5. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Amphetamine and methamphetamine inhalers regarded as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL SPECIAL REQUIREMENTS FOR SPECIFIC HUMAN DRUGS New Drug or Prescription Status of...

  6. Determination of pyrolysis products of smoked methamphetamine mixed with tobacco by tandem mass spectrometry.

    PubMed

    Lee, M R; Jeng, J; Hsiang, W S; Hwang, B H

    1999-01-01

    This study examines the pyrolysis products of smoked methamphetamine mixed with tobacco that was trapped with a C8 adsorbent cartridge and then detected by gas chromatography-tandem mass spectrometry. According to the results, the mainstream smoke contains 2-methylpropyl-benzene, 2-chloropropyl-benzene, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 3-ethyl-phenol, methamphetamine, dimethylamphetamine, hydroquinone, 3-methyl-5-(1-methylethyl)-methylcarbamate phenol, N-methyl-N-(2-phenylethyl)-acetamide, 4-(3-hydroxy-1-butenyl)-3,5,5-trimethyl-2-cyclohexene-1-one, propanoic acid, N-acetylmethamphetamine, phenyl ester, and furfurylmethylamphetamine. In addition, the compounds in sidestream smoke are 2-propenyl benzene, phenylacetone, methamphetamine, dimethylamphetamine, benzyl methyl ketoxime, 3,4-dihydro-2-naphthalenone, N-folmyamphetamine, N-acetylamphetamine, bibenzyl, N-folmylmethamphetamine, N-acetylmethamphetamine, N-propionymethamphetamine, and furfurylmethylamphetamine. Moreover, the presence of methamphetamine promotes the oxidation of the tobacco components. PMID:10022208

  7. Role of the Ventral Tegmental Area in Methamphetamine Extinction: AMPA Receptor-Mediated Neuroplasticity

    ERIC Educational Resources Information Center

    Chen Han-Ting; Chen, Jin-Chung

    2015-01-01

    The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned…

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

    PubMed

    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. PMID:19586151

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

    PubMed Central

    Wood, Evan; Stoltz, Jo-Anne; Montaner, Julio SG; Kerr, Thomas

    2006-01-01

    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. PMID:16723029

  10. Secretory vesicle rebound hyperacidification and increased quantal size due to prolonged methamphetamine exposure

    PubMed Central

    Markov, Dmitriy; Mosharov, Eugene V.; Setlik, Wanda; Gershon, Michael D.; Sulzer, David

    2009-01-01

    Acute exposure to amphetamines collapses secretory vesicle pH gradients, which increases cytosolic catecholamine levels while decreases the quantal size of catecholamine release during fusion events. Amphetamine and methamphetamine, however, are retained in tissues over long durations. We used optical and electron microscopic probes to measure the effects of long-term methamphetamine exposure on secretory vesicle pH, and amperometry and intracellular patch electrochemistry to observe the effects on neurosecretion and cytosolic catecholamines in cultured rat chromaffin cells. In contrast to acute methamphetamine effects, exposure to the drug for 6–48 h at 10 μM and higher concentrations produced a concentration-dependent rebound hyperacidification of secretory vesicles. At 5–10 μM levels, methamphetamine increased the quantal size and reinstated exocytotic catecholamine release, although very high (>100 μM) levels of the drug, while continuing to produce rebound hyperacidification, did not increase quantal size. Secretory vesicle rebound hyperacidification was temperature dependent with optimal response at ~ 37°C, was not blocked by the transcription inhibitor, puromycin, and appears to be a general compensatory response to prolonged exposure with membranophilic weak bases, including amphetamines, methylphenidate, cocaine, and ammonia. Thus, under some conditions of prolonged exposure, amphetamines and other weak bases can enhance, rather than deplete, the vesicular release of catecholamines via a compensatory response resulting in vesicle acidification. PMID:19014382

  11. The Crisis of Methamphetamine and Its Management: Preparation, Participation, and Prevention

    ERIC Educational Resources Information Center

    Cunniff, Judith; Cunniff, Daniel T.; Kay, Kenneth D.

    2008-01-01

    There is a drug crisis in the United States that is growing at an alarming rate. Its participants work in our businesses, government agencies, and schools. California leads the nation in drug use and until recently, Fresno County was the leader in methamphetamine production. This drug crisis is having a paralyzing effect causing loss of income,…

  12. Examining Correlates of Methamphetamine and Other Drug Use in Pregnant American Indian Adolescents

    ERIC Educational Resources Information Center

    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…

  13. A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

    PubMed Central

    Batra, Vinita; Guerin, Glenn F.; Goeders, Nicholas E.; Wilden, Jessica A.

    2016-01-01

    Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID:26863392

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

    PubMed Central

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

    2014-01-01

    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. PMID:25479528

  15. A Meaningful Method: Research with Adolescent Girls Who Use Crystal Methamphetamine

    ERIC Educational Resources Information Center

    Newbury, Janet; Hoskins, Marie L.

    2008-01-01

    Embarking on a study in which we hope to gain a contextualized understanding of the experiences of adolescent girls who use crystal methamphetamines, it is crucial for us to select a research methodology congruent with our aims. In the current article, we share the theoretical basis and decision making process that has lead us to a multi-modal…

  16. Childhood Adverse Events and Health Outcomes among Methamphetamine-Dependent Men and Women

    ERIC Educational Resources Information Center

    Messina, Nena P.; Marinelli-Casey, Patricia; Hillhouse, Maureen; Ang, Alfonso; Hunter, Jeremy; Rawson, Richard

    2008-01-01

    To describe the prevalence of childhood adverse events (CAEs) among methamphetamine-dependent men and women, and assess the relationship of cumulative CAEs to health problems. Data for 236 men and 351 women were analyzed assessing CAEs. Dependent variables included 14 self-reported health problems or psychiatric symptom domains. Mental health was…

  17. Repeated self-mutilation of testicles in the context of methamphetamine use - A case report and brief review of literature.

    PubMed

    Anand, Jacek S; Habrat, Bogusław; Barwina, Małgorzata; Waldman, Wojciech

    2015-02-01

    We report a case of recurrent genital self-mutilation (GSM) after use of methamphetamine. A 29-year-old male with borderline personality and polydrug misuse attempted the GSM twice. Firstly, he self-amputated his left testicle, and one year later he injected printer ink in his right testicle. An open revision of the injured area revealed a puncture wound in the right testicle, with a palpable accumulation of fluid. No ink was found inside the scrotal sac suggesting that the substance was injected directly to the testis. Due to the absence of left testicle, the urologist decided against orchiectomy. Blue colour of serum, urine and sperm was observed for nine days, and then spontaneously disappeared. An ultrasound imaging showed enlargement of the right testis with hypoechogenic fluid/ink collection. Pathomorphological examination of the testicular tissue revealed focal necrosis and diffuse suppurative inflammation of the testicular tunic. Examination of the sperm showed significantly reduced amount of sperm, with majority of dead spermatocytes. Follow-up examination at six months and two years showed absence of spermatocytes. Some attempts of GSM can be repeated. Therefore, specific preventive measures should be undertaken whenever a standard advice and motivational interviewing proved ineffective. Depending on local and general toxicity of an injected xenobiotic, orchiectomy should be considered as a treatment option of GSM. Injection of potentially low toxic ink into the testicle can lead to its permanent damage and infertility. PMID:25623185

  18. CM156, a high affinity sigma ligand, attenuates the stimulant and neurotoxic effects of methamphetamine in mice

    PubMed Central

    Kaushal, Nidhi; Seminerio, Michael J.; Shaikh, Jamaluddin; Medina, Mark A.; Mesangeau, Christophe; Wilson, Lisa L.; McCurdy, Christopher R.; Matsumoto, Rae R.

    2012-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse. Low and high dose administration of METH leads to locomotor stimulation, and dopaminergic and serotonergic neurotoxicity, respectively. The behavioral stimulant and neurotoxic effects of METH can contribute to addiction and other neuropsychiatric disorders, thus necessitating the identification of potential pharmacotherapeutics against these effects produced by METH. METH binds to σ receptors at physiologically relevant concentrations. Also, σ receptors are present on and can modulate dopaminergic and serotonergic neurons. Therefore, σ receptors provide a viable target for the development of pharmacotherapeutics against the adverse effects of METH. In the present study, CM156, a σ receptor ligand with high affinity and selectivity for σ receptors over 80 other non-σ binding sites, was evaluated against METH-induced stimulant, hyperthermic, and neurotoxic effects. Pretreatment of male, Swiss Webster mice with CM156 dose dependently attenuated the locomotor stimulation, hyperthermia, striatal dopamine and serotonin depletions, and striatal dopamine and serotonin transporter reductions produced by METH, without significant effects of CM156 on its own. These results demonstrate the ability of a highly selective σ ligand to mitigate the effects of METH. PMID:21762711

  19. Risky Decision-making: Prefrontal Function and Mesocorticolimbic Resting-state Connectivity in Methamphetamine Users

    PubMed Central

    Kohno, Milky; Morales, Angelica M.; Ghahremani, Dara G.; Hellemann, Gerhard; London, Edythe D.

    2014-01-01

    Importance Various neuropsychiatric disorders, especially addictions, feature impairments in risky decision-making; clarifying the neural mechanisms underlying this problem can inform treatment. Objective To determine how methamphetamine-dependent and control subjects differ in brain activation during a risky decision-making task, resting-state functional connectivity within mesolimbic and executive control circuits, and the relationships between these measures. Design A case-control, functional magnetic resonance imaging study of methamphetamine-dependent and healthy comparison participants at rest and when performing the Balloon Analogue Risk Task, which involves the choice to pump a balloon or to cash out in the context of uncertain risk. Setting Clinical research center at an academic institution. Participants Twenty-five methamphetamine-dependent and 27 control subjects. Main Outcomes and Measures 1) Parametric modulation of activation in the striatum and right dorsolateral prefrontal cortex, i.e., the degree to which activation changed as a linear function of risk and potential reward, both indexed by pump number; and 2) resting-state functional connectivity, measured in whole brain with seeds in the midbrain and right dorsolateral prefrontal cortex. Relationships between these outcomes were also tested. Results Parametric modulation of cortical and striatal activation by pump number during risk-taking differed with group. It was stronger in the ventral striatum but weaker in the right dorsolateral prefrontal cortex in methamphetamine-dependent participants than controls. Methamphetamine-dependent subjects also exhibited greater resting-state functional connectivity of the midbrain with the putamen, amygdala, and hippocampus. This connectivity was negatively related to modulation of right dorsolateral prefrontal cortex activation by risk level during risky decision-making. In controls, parametric modulation of right dorsolateral prefrontal cortex activation

  20. Methamphetamine Self-Administration Causes Persistent Striatal Dopaminergic Alterations and Mitigates the Deficits Caused by a Subsequent Methamphetamine Exposure

    PubMed Central

    McFadden, Lisa M.; Hadlock, Greg C.; Allen, Scott C.; Vieira-Brock, Paula L.; Stout, Kristen A.; Ellis, Jonathan D.; Hoonakker, Amanda J.; Andrenyak, David M.; Nielsen, Shannon M.; Wilkins, Diana G.; Hanson, Glen R.

    2012-01-01

    Preclinical studies have demonstrated that repeated methamphetamine (METH) injections (referred to herein as a “binge” treatment) cause persistent dopaminergic deficits. A few studies have also examined the persistent neurochemical impact of METH self-administration in rats, but with variable results. These latter studies are important because: 1) they have relevance to the study of METH abuse; and 2) the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure. Accordingly, the present study investigated the impact of METH self-administration on dopaminergic neuronal function. Results revealed that self-administration of METH, given according to a regimen that produces brain METH levels comparable with those reported postmortem in human METH abusers (0.06 mg/infusion; 8-h sessions for 7 days), decreased striatal dopamine transporter (DAT) uptake and/or immunoreactivity as assessed 8 or 30 days after the last self-administration session. Increasing the METH dose per infusion did not exacerbate these deficits. These deficits were similar in magnitude to decreases in DAT densities reported in imaging studies of abstinent METH abusers. It is noteworthy that METH self-administration mitigated the persistent deficits in dopaminergic neuronal function, as well as the increases in glial fibrillary acidic protein immunoreactivity, caused by a subsequent binge METH exposure. This protection was independent of alterations in METH pharmacokinetics, but may have been attributable (at least in part) to a pretreatment-induced attenuation of binge-induced hyperthermia. Taken together, these results may provide insight into the neurochemical deficits reported in human METH abusers. PMID:22034657

  1. Profound reduction in sensitivity to the aversive effects of methamphetamine in mice bred for high methamphetamine intake

    PubMed Central

    Shabani, Shkelzen; McKinnon, Carrie S.; Cunningham, Christopher L.; Phillips, Tamara J.

    2011-01-01

    Reduced sensitivity to aversive effects of methamphetamine (MA) may increase risk for MA abuse. Studies in two replicate sets of mouse lines that were selectively bred for high and low levels of MA intake support this view. Current studies examined the extent of insensitivity to aversive MA effects of mice bred for high levels of MA drinking. Conditioning procedures in which drugs are delivered shortly after cue exposure have been used to detect aversive drug effects and, in some cases, are more sensitive to such effects. Aversive effects induced by MA injected immediately after exposure to cues from two different sensory modalities were examined. In addition, effects of higher MA doses than those used previously were examined. MA-associated place conditioning utilized tactile cues, whereas MA-induced taste conditioning utilized a novel tastant. Second replicate, MA high drinking (MAHDR-2) and low drinking (MALDR-2) mice were treated with doses of MA up to 4 mg/kg. MAHDR-2 mice were insensitive to aversive effects of MA, except after place conditioning with the 4 mg/kg dose; MALDR-2 mice exhibited sensitivity to aversive effects of MA at doses as low as 1 mg/kg. These studies show that the expression of aversion is dependent upon procedure and MA dose, and that MAHDR-2 mice have markedly reduced sensitivity to the aversive effects of MA. The current and previous results support a strong genetic relationship between level of MA intake and level of sensitivity to aversive effects of MA, a factor that could impact risk for MA use in humans. PMID:22118879

  2. Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement.

    PubMed

    Gong, Xiaokang; Yue, Kai; Ma, Baomiao; Xing, Junqiao; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying

    2016-05-01

    Despite the high prevalence of methamphetamine (METH) use, no FDA-approved pharmacological treatment is currently available for individuals with a METH addiction. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance derived from corydalis and stephania that has been used in traditional Asian medicine for its analgesic, sedative and hypnotic properties. Previous pharmacological studies of l-THP indicated that it not only binds to D1 and D2 receptors but also has a low affinity for D3 receptors and may function as an antagonist. The unique pharmacological profile of l-THP suggests that it may have potential therapeutic effects on drug addiction; however, the effects of l-THP in individuals with METH addictions are largely unknown. In this study, we investigated the effects of l-THP on METH self-administration and METH-induced reinstatement. In our experiments, l-THP (1.25, 2.50 and 5.00 mg/kg, i.p.) decreased METH self-administration under the fixed-ratio 1 schedule. l-THP (2.50 and 5.00 mg/kg, i.p) also prevented the METH-induced reinstatement of METH-seeking behaviors. Interestingly, l-THP (1.25 and 2.50mg/kg, i.p) did not affect locomotor activity following METH injection (1mg/kg) suggesting that the observed effects of l-THP (2.50mg/kg) on METH-induced reinstatement were not due to motor impairments. Thus, l-THP (a natural, mixed dopamine (DA) receptor antagonist) attenuates METH self-administration and METH-induced reinstatement. PMID:26806555

  3. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

    PubMed

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; Flegel, Ron; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-10-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation. PMID:25217541

  4. Developing a Text Messaging Risk Reduction Intervention for Methamphetamine-Using MSM: Research Note

    PubMed Central

    Reback, Cathy J; Ling, Deborah; Shoptaw, Steven; Rohde, Jane

    2010-01-01

    Men who have sex with men (MSM) who use methamphetamine experience high risks for HIV infection due to sexual transmission behaviors often engaged in when under the influence of methamphetamine. Methamphetamine-using MSM use various forms of information technology (IT) communication such as instant messaging, social networking sites, and websites to facilitate a sexual and/or drug “hook up.” Given the acceptability of IT communication in their daily lives, an IT intervention represents an appropriate strategy to reach and intervene with out-of-treatment, methamphetamine-using MSM. The aim of this study was to conduct formative work to develop a text messaging intervention to reduce methamphetamine use and high-risk sexual behaviors among out-of-treatment MSM, which involved conducting focus groups, community partners’ meetings, and a pre-test intervention. These activities culminated in the development of a two-week, text-messaging intervention that delivered real-time electronic correspondence based on the behavioral change theories of Social Support Theory, Health Belief Model, and Social Cognitive Theory. The focus groups, community meetings, and pre-test were used to identify the IT communication device, the text messages that best support risk reduction and healthier behavioral choices, and logo, flyer and website development. The input and feedback from the target population and community partners were critical to the successful development of a culturally appropriate intervention. The knowledge gleaned from the formative work of this study will be vitally helpful in designing future IT studies. PMID:20657827

  5. A Study of the Prevalence of Psychiatric Disorders in Patients with Methamphetamine-Induced Psychosis

    PubMed Central

    Eslami-Shahrbabaki, Mahin; Fekrat, Alireza; Mazhari, Shahrzad

    2015-01-01

    Background The abuse of narcotic drugs and psychotropic substances such as amphetamines and ecstasy has had a growing trend. Tachycardia, increased blood pressure, hallucinations, panic attacks, and psychosis are the negative effects of methamphetamine abuse. The present study aimed to assess psychiatric disorders associated with methamphetamine-induced psychotic disorder. Methods This cross-sectional study was performed from October 2013 to March 2014 on 165 patients hospitalized at Shahid Beheshti Hospital in Kerman, Iran, and diagnosed with psychosis induced by methamphetamine abuse within the previous 6 months. Study subjects were selected via census method. Based on the exclusion criteria and due to the lack of cooperation of some patients, 121 patients were enrolled in the study. Research data were gathered using clinical interviews, the Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton anxiety scale (HAM-A) and Hamilton rating scale for depression (HRSD), Young mania rating scale (YMRS), substance dependence severity scale (SDSS), positive and negative syndrome scale (PANSS), and clinical global impression (CGI) scale. The data analysis was performed using SPSS software, descriptive statistics, and ANOVA. Findings Among the 121 patients of the sample group, 4 patients (3.3%) had anxiety, 58 patients (47.9%) depression, 30 patients (24.8%) obsessive-compulsive disorder (OCD), 20 patients (16.5%) bipolar mood disorder (BMD), 8 patients (6.6%) persistent psychotic symptoms, 85 patients (70.2%) personality disorder, and 36 patients (29.8%) had no personality disorders. The highest prevalence was related to borderline personality disorder (35.5%). However, 45 patients (37.2%) had no impairment associated with methamphetamine-induced psychosis. Conclusion It seems that there is comorbidity between psychiatric disorders, including mood disorders, especially depressive disorder, childhood history of attention deficit hyperactivity disorder (ADHD), bipolar

  6. The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population

    PubMed Central

    Kishimoto, Makiko; Ujike, Hiroshi; Okahisa, Yuko; Kotaka, Tatsuya; Takaki, Manabu; Kodama, Masafumi; Inada, Toshiya; Yamada, Mitsuhiko; Uchimura, Naohisa; Iwata, Nakao; Sora, Ichiro; Iyo, Masaomi; Ozaki, Norio; Kuroda, Shigetoshi

    2008-01-01

    Background Frizzled 3 (Fzd3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia. Methods Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls. Results A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis. Conclusion Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis. PMID:18702828

  7. Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats

    PubMed Central

    Miller, ML; Aarde, SM; Moreno, AY; Creehan, KM; Janda, KD; Taffe, MA

    2015-01-01

    BACKGROUND D-methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects of METH. The current study investigated whether active vaccination against METH could alter intravenous METH self-administration in rats. METHODS Male Sprague-Dawley rats (Experiment 1: N=24; Experiment 2: N=18) were vaccinated with either a control keyhole-limpet hemocyanin conjugate vaccine (KLH) or a candidate anti-METH vaccine (MH6-KLH) or. Effects of vaccination on the acquisition of METH self-administration under two dose conditions (0.05, 0.1 mg/kg/inf) and post-acquisition dose-substitution (0, 0.01, 0.05, 0.20 mg/kg/inf, Experiment 1; 0.01, 0.05, 0.10, 0.15 mg/kg/inf, Experiment 2) during steady-state responding were investigated. Plasma METH concentrations were determined 30 min after an acute challenge dose of 3.2 mg/kg METH. RESULTS Active vaccination inhibited the acquisition of METH self-administration under the 0.1 mg/kg/inf dose condition, with 66% of the MH6-KLH-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Under the 0.05 mg/kg/inf dose condition, MH6-KLH-vaccinated rats initially self-administered more METH than controls, but then self-administration decreased across the acquisition phase relative to controls; a subsequent dose-response assessment confirmed that MH6-KLH-vaccinated rats failed to acquire METH self-administration. Finally, plasma METH concentrations were higher in MH6-KLH-vaccinated rats compared to controls after an acute METH challenge, and these were positively correlated with antibody titers. CONCLUSIONS These data demonstrate that active immunopharmacotherapy for METH attenuates the acquisition of METH self-administration. PMID:26118833

  8. Development and Preclinical Testing of a High Affinity Single Chain Antibody against (+)-Methamphetamine

    PubMed Central

    Peterson, Eric C.; Laurenzana, Elizabeth M.; Atchley, William T.; Hendrickson, Howard; Owens, S. Michael

    2009-01-01

    Chronic or excessive (+)-methamphetamine (METH) use often leads to addiction and toxicity to critical organs like the brain. With medical treatment as a goal, a novel single chain variable fragment (scFv) against METH was engineered from anti-METH monoclonal antibody mAb6H4 (IgG, κ light chain, KD = 11 nM) and found to have similar ligand affinity (KD = 10 nM) and specificity as mAb6H4. The anti-METH scFv (scFv6H4) was cloned, expressed in yeast, purified and formulated as a naturally occurring mixture of monomer (~75%) and dimer (~25%). To test the in vivo efficacy of the scFv6H4, male Sprague Dawley rats (n=5) were implanted with 3-day sc osmotic pumps delivering 3.2 mg/kg/day METH. After reaching steady-state METH concentrations, an i.v. dose of scFv6H4 (36.5 mg/kg, equimolar to the METH body burden) was administered along with a [3H]-scFv6H4 tracer. Serum pharmacokinetic (PCKN) analysis of METH and [3H]-scFv6H4 showed that the scFv6H4 caused an immediate 65-fold increase in the METH concentrations and a 12-fold increase in the serum METH area under the concentration-time curve from 0–480 min after scFv6H4 administration. The scFv6H4 monomer was quickly cleared or converted to multivalent forms with an apparent t1/2λz of 5.8 min. In contrast, the larger scFv6H4 multivalent forms (dimers, trimers, etc.) showed a much longer t1/2λz (228 min), and the significantly increased METH serum molar concentrations correlated directly with scFv6H4 serum molar concentrations. Considered together these data suggested that the scFv6H4 multimers (and not the monomer) were responsible for the prolonged redistribution of METH into the serum. PMID:18192498

  9. The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour

    PubMed Central

    Baracz, Sarah Jane; Everett, Nicholas Adams; Cornish, Jennifer Louise

    2015-01-01

    The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol) or co-administration of oxytocin (3.6 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (3 nmol) into the STh (200 nl/side) was examined on METH-primed reinstatement (1 mg/kg; i.p.). We found that local administration of the highest oxytocin dose (3.6 pmol) into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse. PMID:26284529

  10. Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.

    PubMed

    Baracz, Sarah J; Everett, Nicholas A; McGregor, Iain S; Cornish, Jennifer L

    2016-03-01

    The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague-Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae in the NAc core. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5 pmol, 1.5 pmol, 4.5 pmol) or co-administration of oxytocin (1.5 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1 nmol, 3 nmol) in the NAc core (500 nl/side) was examined on METH-primed (1 mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking. PMID:25399704

  11. Methamphetamine Users Have Increased Dental Disease: A Propensity Score Analysis.

    PubMed

    Shetty, V; Harrell, L; Clague, J; Murphy, D A; Dye, B A; Belin, T R

    2016-07-01

    Methamphetamine (MA) users are assumed to have a high burden of tooth decay. Less clear is how the distribution and severity of dental caries in MA users differ from the general population. Using a covariate-balancing propensity score strategy, we investigated the differential effects of MA use on dental caries by comparing the patterns of decayed, missing, and filled teeth in a community sample of 571 MA users with a subset of 2,755 demographically similar control individuals selected from a National Health and Nutrition Examination Survey (NHANES) cohort. Recruited over a 2-y period with a stratified sampling protocol, the MA users underwent comprehensive dental examinations by 3 trained and calibrated dentists using NHANES protocols. Propensity scores were estimated with logistic regression based on background characteristics, and a subset of closely matched subjects was stratified into quintiles for comparisons. MA users were twice as likely to have untreated caries (odds ratio [OR] = 2.08; 95% confidence interval [95% CI]: 1.55 to 2.78) and 4 times more likely to have caries experience (OR = 4.06; 95% CI: 2.24 to 7.34) than the control group of NHANES participants. Additionally, MA users were twice as likely to have 2 more decayed, missing, or filled teeth (OR = 2.08; 95% CI: 1.29 to 2.79) than the NHANES participants. The differential involvement of the teeth surfaces in MA users was quite distinctive, with carious surface involvement being highest for the maxillary central incisors, followed by maxillary posterior premolars and molars. Users injecting MA had significantly higher rates of tooth decay compared with noninjectors (P = 0.04). Although MA users experienced decayed and missing dental surfaces more frequently than NHANES participants, NHANES participants had more restored surfaces, especially on molars. The high rates and distinctive patterns of dental caries observed could be used 1) to alert dentists to covert MA use in their patients and 2) as

  12. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    PubMed

    Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  13. An animal model of differential genetic risk for methamphetamine intake

    PubMed Central

    Phillips, Tamara J.; Shabani, Shkelzen

    2015-01-01

    The question of whether genetic factors contribute to risk for methamphetamine (MA) use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine-associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1) agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the development of a

  14. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    PubMed Central

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  15. The relationship between methamphetamine use and increased dental disease

    PubMed Central

    Shetty, Vivek; Mooney, Larissa J.; Zigler, Corwin M.; Belin, Thomas R.; Murphy, Debra; Rawson, Richard

    2010-01-01

    Background Methamphetamine (MA) use has been linked anecdotally to rampant dental disease. The authors sought to determine the relative prevalence of dental comorbidities in MA users, verify whether MA users have more quantifiable dental disease and report having more dental problems than nonusers and establish the influence of mode of MA administration on oral health outcomes. Methods Participating physicians provided comprehensive medical and oral assessments for adults dependent on MA (n = 301). Trained interviewers collected patients' self-reports regarding oral health and substance-use behaviors. The authors used propensity score matching to create a matched comparison group of nonusers from participants in the the Third National Health and Nutrition Examination Survey (NHANES III). Results Dental or oral disease was one of the most prevalent (41.3 percent) medical cormorbidities in MA users who otherwise were generally healthy. On average, MA users had significantly more missing teeth than did matched NHANES III control participants (4.58 versus 1.96, P < .001) and were more likely to report having oral health problems (P < .001). Significant subsets of MA users expressed concerns with their dental appearance (28.6 percent), problems with broken or loose teeth (23.3 percent) and tooth grinding (bruxism) or erosion (22.3 percent). The intravenous use of MA was significantly more likely to be associated with missing teeth than was smoking MA (odds ratio = 2.47; 95 percent confidence interval = 1.3-4.8). Conclusions Overt dental disease is one of the key distinguishing comorbidities in MA users. MA users have demonstrably higher rates of dental disease and report long-term unmet oral health needs. Contrary to common perception, users who smoke or inhale MA have lower rates of dental disease than do those who inject the drug. Many MA users are concerned with the cosmetic aspects of their dental disease, and these concerns could be used as behavioral triggers for

  16. Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

    PubMed Central

    Castelli, M. Paola; Casu, Angelo; Casti, Paola; Scherma, Maria; Fattore, Liana; Fadda, Paola; Ennas, M. Grazia

    2014-01-01

    Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS), production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4×10 mg/kg, 2 hours apart) were pre- or post-treated with Δ9-THC (1 or 3 mg/kg) and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP). Results showed that, as compared to corresponding controls (i) METH-induced nNOS overexpression in the caudate-putamen (CPu) was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (−19% and −28% for 1 mg/kg pre- and post-treated animals; −25% and −21% for 3 mg/kg pre- and post-treated animals); (ii) METH-induced GFAP-immunoreactivity (IR) was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (−50%) and by pre-treatment with 3 mg/kg Δ9-THC (−53%); (iii) METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC) by pre- and post-treatment with both doses of Δ9-THC (−34% and −47% for 1 mg/kg pre- and post-treated animals; −37% and −29% for 3 mg/kg pre- and post-treated animals). The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the

  17. Duration of detection of methamphetamine in hair after abstinence.

    PubMed

    Suwannachom, Natiprada; Thananchai, Thiwaphorn; Junkuy, Anongphan; O'Brien, Timothy E; Sribanditmongkol, Pongruk

    2015-09-01

    Researchers in the field of hair analysis have known for at least two decades that test results for many chemical compounds remain positive for a considerable period of time after subjects have reported cessation of use. These findings were generally based on small sample populations or individual case studies. Within the last decade, hair analyses of larger populations have investigated the phenomenon of residual positives in abstinent individuals in order to determine the period of time required for various compounds to present negative hair test results at internationally accepted cutoff levels. Such data has primarily been used to establish guidelines for retesting former abusers of illicit drugs in order to evaluate claims of abstinence. To date, research has focused on cocaine and opiates. The present study is the first to examine the duration of detection of methamphetamine (MA) and its metabolite amphetamine (AP) in the hair of chronic MA users who recently ceased their consumption of the drug. The study population (n=63) consisted of inpatients at a hospital drug rehabilitation program in Chiang Mai, Thailand. Drug taking behavior was collected by personal interview at the time of enrollment. Subjects provided hair samples at approximately monthly intervals for MA and AP analysis by gas chromatography-mass spectrometry at 0.2ng/mg cutoff levels. The correlation of baseline MA and AP concentrations in hair at the beginning of abstinence with corresponding duration of detection indicated great individual variability for the rate of clearance of MA and AP from hair. In regard to duration of detection, the majority of chronic MA users remained MA positive for up to about 90 days of reported abstinence, but by 120 days, the detection rate had fallen to about 16%. All subjects tested negative for MA after 153 days of abstinence. For AP, the limit of the duration of detection was reached at 106 days. With the adoption of a margin of safety to compensate for

  18. Methamphetamine abstinence induces changes in μ-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype.

    PubMed

    Georgiou, Polymnia; Zanos, Panos; Garcia-Carmona, Juan-Antonio; Hourani, Susanna; Kitchen, Ian; Laorden, Maria-Luisa; Bailey, Alexis

    2016-06-01

    The major challenge in treating methamphetamine addicts is the maintenance of a drug free-state since they experience negative emotional symptoms during abstinence, which may trigger relapse. The neuronal mechanisms underlying long-term withdrawal and relapse are currently not well-understood. There is evidence suggesting a role of the oxytocin (OTR), μ-opioid receptor (MOPr), dopamine D2 receptor (D2R), corticotropin-releasing factor (CRF) systems and the hypothalamic-pituitary-adrenal (HPA)-axis in the different stages of methamphetamine addiction. In this study, we aimed to characterize the behavioral effects of methamphetamine withdrawal in mice and to assess the modulation of the OTR, MOPr, D2R, CRF and HPA-axis following chronic methamphetamine administration and withdrawal. Ten-day methamphetamine administration (2 mg/kg) increased OTR binding in the amygdala, whilst 7 days of withdrawal induced an upregulation of this receptor in the lateral septum. Chronic methamphetamine treatment increased plasma OT levels that returned to control levels following withdrawal. In addition, methamphetamine administration and withdrawal increased striatal MOPr binding, as well as c-Fos(+)/CRF(+) neuronal expression in the amygdala, whereas an increase in plasma corticosterone levels was observed following METH administration, but not withdrawal. No differences were observed in the D2R binding following METH administration and withdrawal. The alterations in the OTR, MOPr and CRF systems occurred concomitantly with the emergence of anxiety-related symptoms and the development of psychomotor sensitization during withdrawal. Collectively, our findings indicate that chronic methamphetamine use and abstinence can induce brain-region specific neuroadaptations of the OTR, MOPr and CRF systems, which may, at least, partly explain the withdrawal-related anxiogenic effects. PMID:26896754

  19. Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1

    PubMed Central

    Achat-Mendes, Cindy; Lynch, Laurie J.; Sullivan, Katherine A.; Vallender, Eric J.; Miller, Gregory M.

    2011-01-01

    The trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that is functionally activated by amphetamine-based psychostimulants, including amphetamine, methamphetamine and MDMA. Previous studies have shown that in transgenic mice lacking the TAAR1 gene (TAAR1 knockout; KO) a single injection of amphetamine can produce enhanced behavioral responses compared to responses evoked in wild-type (WT) mice. Further, the psychostimulant effects of cocaine can be diminished by selective activation of TAAR1. These findings suggest that TAAR1 might be implicated in the rewarding properties of psychostimulants. To investigate the role of TAAR1 in the rewarding effects of drugs of abuse, the psychomotor stimulating effects of amphetamine and methamphetamine and the conditioned rewarding effects of methamphetamine and morphine were compared between WT and TAAR1 KO mice. In locomotor activity studies, both single and repeated exposure to d-amphetamine or methamphetamine generated significantly higher levels of total distance travelled in TAAR1 KO mice compared to WT mice. In conditioned place preference (CPP) studies, TAAR1 KO mice acquired methamphetamine-induced CPP earlier than WT mice and retained CPP longer during extinction training. In orphine-induced CPP, both WT and KO genotypes displayed similar levels of CPP. Results from locomotor activity studies suggest that TAAR1 may have a modulatory role in the behavioral sensitization to amphetamine-based psychostimulants. That methamphetamine- but not morphine-induced CPP was augmented in TAAR1 KO mice suggests a selective role of TAAR1 in the conditioned reinforcing effects of methamphetamine. Collectively, these findings provide support for a regulatory role of TAAR1 in methamphetamine signaling. PMID:22079347

  20. Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1.

    PubMed

    Achat-Mendes, Cindy; Lynch, Laurie J; Sullivan, Katherine A; Vallender, Eric J; Miller, Gregory M

    2012-04-01

    The trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that is functionally activated by amphetamine-based psychostimulants, including amphetamine, methamphetamine and MDMA. Previous studies have shown that in transgenic mice lacking the TAAR1 gene (TAAR1 knockout; KO) a single injection of amphetamine can produce enhanced behavioral responses compared to responses evoked in wild-type (WT) mice. Further, the psychostimulant effects of cocaine can be diminished by selective activation of TAAR1. These findings suggest that TAAR1 might be implicated in the rewarding properties of psychostimulants. To investigate the role of TAAR1 in the rewarding effects of drugs of abuse, the psychomotor stimulating effects of amphetamine and methamphetamine and the conditioned rewarding effects of methamphetamine and morphine were compared between WT and TAAR1 KO mice. In locomotor activity studies, both single and repeated exposure to d-amphetamine or methamphetamine generated significantly higher levels of total distance traveled in TAAR1 KO mice compared to WT mice. In conditioned place preference (CPP) studies, TAAR1 KO mice acquired methamphetamine-induced CPP earlier than WT mice and retained CPP longer during extinction training. In morphine-induced CPP, both WT and KO genotypes displayed similar levels of CPP. Results from locomotor activity studies suggest that TAAR1 may have a modulatory role in the behavioral sensitization to amphetamine-based psychostimulants. That methamphetamine-but not morphine-induced CPP was augmented in TAAR1 KO mice suggests a selective role of TAAR1 in the conditioned reinforcing effects of methamphetamine. Collectively, these findings provide support for a regulatory role of TAAR1 in methamphetamine signaling. PMID:22079347

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

    PubMed

    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. PMID:27325011

  2. Association between the Regulator of G-protein Signaling 9 Gene and Patients with Methamphetamine Use Disorder and Schizophrenia

    PubMed Central

    Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Ujike, H

    2011-01-01

    The regulator of G-protein signaling (RGS) modulates the functioning of heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a role in modulating dopaminergic receptor-mediated signaling cascades. Previous studies suggested that the RGS9 gene might contribute to the susceptibility to psychotic diseases. Therefore, we investigated the association between the RGS9 gene and two related dopamine psychoses, schizophrenia and methamphetamine use disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and sex-matched healthy controls and 220 patients of methamphetamine use disorder and 289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285 (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed monomorphism in the present Japanese population, but rs12452285 showed polymorphism. There were no significant differences in genotypic or allelic distributions of rs12452285 between patients with schizophrenia and the corresponding control or between patients with methamphetamine use disorder and the corresponding control. We also analyzed the clinical features of methamphetamine use disorder. We found a significant association in allelic distribution with the phenotypes of age at first consumption (p=0.047). The present study suggested that the RGS9 gene is unlikely to play a major role in schizophrenia and methamphetamine dependence liability and/or the development of methamphetamine induced psychosis, at least in a Japanese population. PMID:21886588

  3. Psychosocial treatment for methamphetamine use disorders: a preliminary randomized controlled trial of cognitive behavior therapy and Acceptance and Commitment Therapy.

    PubMed

    Smout, Matthew F; Longo, Marie; Harrison, Sonia; Minniti, Rinaldo; Wickes, Wendy; White, Jason M

    2010-04-01

    Acceptance and Commitment Therapy (ACT) incorporates developments in behavior therapy, holds promise but has not been evaluated for methamphetamine use disorders. The objective of this study was to test whether ACT would increase treatment attendance and reduce methamphetamine use and related harms compared to cognitive behavior therapy (CBT). One hundred and four treatment-seeking adults with methamphetamine abuse or dependence were randomly assigned to receive 12 weekly 60-minute individual sessions of ACT or CBT. Attrition was 70% at 12 weeks and 86% at 24 weeks postentry. Per intention-to-treat analysis, there were no significant differences between the treatment groups in treatment attendance (median 3 sessions), and methamphetamine-related outcomes; however, methamphetamine use (toxicology-assessed and self-reported), negative consequences, and dependence severity significantly improved over time in both groups. Although ACT did not improve treatment outcomes or attendance compared to CBT, it may be a viable alternative to CBT for methamphetamine use disorders. Future rigorous research in this area seems warranted. PMID:20408061

  4. Maternal separation fails to render animals more susceptible to methamphetamine-induced conditioned place preference.

    PubMed

    Faure, Jacqueline; Stein, Dan J; Daniels, William

    2009-12-01

    The maternal separation (MS) paradigm is an animal model that has been successfully used to study the long term effects of child abuse and neglect. Experiments showed that animals subjected to trauma and stress early in life display behavioural, endocrinological and growth factor abnormalities at a later stage in life, results that mirrored clinical conditions. It is apparent that adverse events early in life may affect the development and maturation of the brain negatively. The purpose of the present study was to investigate whether the abnormal brain development occurring in separated animals would also enhance the development of a preference for psychostimulant drug usage. Rats were subjected to maternal deprivation and further exposed to methamphetamine-induced conditioned place preference (CPP) which primarily measures drug reward (ventral striatum) learning and memory. Apomorphine-induced locomotor activity was also assessed to investigate the effects of methamphetamine on the dorsal (primarily locomotor activity) striatal dopaminergic system. We found that four consecutive injections of methamphetamine resulted in CPP behaviour 24 h after the 4th injection. A further four injections yielded similar CPP results and this effect lasted for at least 7 days until the third CPP assessment. These animals also had decreased ACTH and corticosterone secretions, but the prolactin levels were increased. Prior exposure to maternal separation did not have any effect on the CPP test. The ACTH and corticosterone secretions were also similarly reduced. However maternal separation decreased the release of prolactin and this reduction was not evident in the separated group that received methamphetamine. There was no significant difference in the apomorphine-induced locomotor activity of normally reared animals whether they received methamphetamine or saline. Interestingly there was a significant difference in locomotor activity between the two groups of animals that were

  5. Theories of Addiction: Methamphetamine Users’ Explanations for Continuing Drug Use and Relapse

    PubMed Central

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

    2012-01-01

    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

  6. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats

    PubMed Central

    Huang, Pai-Kai; Aarde, Shawn M.; Angrish, Deepshikha; Houseknecht, Karen L.; Dickerson, Tobin J.; Taffe, Michael A.

    2012-01-01

    BACKGROUND Reports from US, UK and European drug policy entities, and ongoing media accounts, show increasing recreational use of 4-methylmethcathinone (4-MMC, mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV). Severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported, yet little scientific information is available on the effects of these compounds in laboratory models. Available studies on the neurochemistry of these drugs show that 4-MMC and MDPV enhance DA neurotransmission, while 4-MMC additionally enhances 5-HT neurotransmission- a pattern much like that reported for methamphetamine vs. 3,4-methylenedioxymethamphetamine (MDMA). As is the case for designer amphetamines, these neurochemical distinctions may predict differential potential for repetitive versus episodic abuse and distinct lasting toxicities. METHODS This study determined relative locomotor stimulant effects of 4-MMC (1–10 mg/kg, s.c.) and MDPV (0.5–5.6 mg/kg, s.c.), in comparison with d-methamphetamine (MA; 0.5–5.6 mg/kg, s.c.) and MDMA (1–7.5 mg/kg, s.c.) on a measure of locomotor activity – voluntary wheel running – in male Wistar rats (N=8). RESULTS Compared to counts of wheel rotations after saline, a biphasic change in the pattern of counts was observed after injections of MA and MDPV, with relatively higher counts following lower doses and lower counts following the highest dose. However, monophasic, dose-dependent reductions in counts were observed in response to injections of MDMA and 4-MMC. CONCLUSION Thus, voluntary wheel running yielded the same categorical distinctions for these drugs as did prior experiments testing the effects of these drugs on monoaminergic neurotransmission. These data indicate that MDPV produces prototypical locomotor stimulant effects whereas 4-MMC is more similar to the entactogen MDMA. PMID:22664136

  7. Male Osteoporosis

    PubMed Central

    Drake, Matthew T.; Khosla, Sundeep

    2013-01-01

    Synopsis Osteoporosis is now recognized as a major threat to health in aging men. Morbidity and mortality, particularly following hip fracture, are substantial. Whereas trabecular bone loss starts in early adulthood, loss of cortical bone only appears to occur from mid-life onwards. Declining bioavailable estradiol levels play an integral role in male age-associated bone loss. Both pharmacologic and supportive care interventions are important for optimal care in men at increased fracture risk. PMID:22877433

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

    PubMed

    Sirova, Jana; Kristofikova, Zdenka; Vrajova, Monika; Fujakova-Lipski, Michaela; Ripova, Daniela; Klaschka, Jan; Slamberova, Romana

    2016-08-01

    Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to

  9. Lead poisoning associated with intravenous-methamphetamine use--Oregon, 1988

    SciTech Connect

    Chandler, D.B.; Norton, R.L. ); Kauffman, K.W.; Gordon, J.; Foster, L.R.

    1990-02-09

    Between August 1 and September 6, 1988, 14 cases of non-A, non-B (NANB) hepatitis were reported in Marion County, Oregon, to the Oregon Health Division (OHD) by the county health department and private physicians. Previously, an average of less than one case per month was reported in the county. During the same period, OHD learned that eight intravenous-methamphetamine users (IVMUs) in Oregon thought to have NANB hepatitis had also been recently diagnosed with lead poisoning. A statewide media campaign describing the lead poisoning outbreak was conducted to alert IVMUs, physicians, and county health departments. In addition, OHD implemented a reporting system for suspected and confirmed lead poisoning cases. Analysis of an illicit methamphetamine sample provided by one of the patients with confirmed lead poisoning detected 60% lead by weight.

  10. The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes.

    PubMed

    Mohawk, Jennifer A; Baer, Matthew L; Menaker, Michael

    2009-03-01

    The "master clock" in the suprachiasmatic nucleus (SCN) of the hypothalamus controls most behavioral, physiological, and molecular circadian rhythms in mammals. However, there are other, still unidentified, circadian oscillators that are able to carry out some SCN functions. Here we show that one of these, the methamphetamine-sensitive circadian oscillator (MASCO), which generates behavioral rhythms in the absence of the SCN, is based on an entirely different molecular mechanism. We tested mice lacking, or with mutations of, genes that form the canonical circadian machinery. In all cases, animals that were arrhythmic as a consequence of genetic defect expressed circadian locomotor rhythms when treated with methamphetamine. These results strongly support the hypothesis that the mechanism generating MASCO does not involve the molecular feedback loops that underlie canonical circadian rhythmicity. The properties of MASCO may provide insight into the evolution of circadian mechanisms. Importantly, MASCO may play a role in addiction to psychostimulants. PMID:19204282

  11. Ranitidine interference with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay.

    PubMed

    Poklis, A; Hall, K V; Still, J; Binder, S R

    1991-01-01

    The interference of ranitidine with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay (ME) was investigated. Urine specimens collected from 23 patients receiving 150-300 mg of ranitidine daily were found to contain 7-271 mg/L of the drug when analyzed by Remedi automated high pressure liquid chromatography. Only patient specimens and urine samples with ranitidine added at concentrations greater than 91 mg/L gave false positive ME results. Of the 63 patient urine samples analyzed by ME, 12 gave false positive results. All false positive results occurred in the first or second void after ingestion. No false positive results occurred with the polyclonal EMIT d.a.u. amphetamine or TDx amphetamine/methamphetamine II assays. PMID:2051743

  12. Personality Traits and Identity Styles in Methamphetamine-Dependent Women: A Comparative Study

    PubMed Central

    Hojjat, Seyed Kaveh; Golmakani, Ebrahim; Bayazi, Mohammad Hossein; Mortazavi, Razieh; Khalili, Mina Norozi; Akaberi, Arash

    2016-01-01

    Background: Studies over the past two decades have shown that various personality traits of substance-dependent men measure differently than compared to normal individuals. However fewer studies have addressed the role of identity as an influential factor in the onset and continuation of drug dependency. Methods: The objective of this study was to compare the Big Five personality factors and identity styles in methamphetamine dependent women and non-user group. Forty eight methamphetamine dependent women under treatment in Welfare Organization’s residential centers filled out the NEO Five-Factor Inventory (NEO-FFI) and the Berzonsky’s Identity Style Inventory. They were compared with 48 non-dependent women who were matched in terms of age, education, marital status, and occupation. Data was analyzed with t student test. Statistical analyses were performed using the SPSS V.16 software. Differences were considered significant at P<0.05. Results: Results found that methamphetamine dependent woman had significantly higher levels of neuroticism and lower levels of conscientiousness, agreeableness and openness to experience compared to normative sample of female respondents. In addition, mean scores of diffuse/avoidant identity style in methamphetamine user women was significantly higher than non-user group. This is while non-user women had a significantly higher mean in normative identity style. Conclusion: Identity styles along with personality traits can be a key role in drug use in women in this study. Therefore, enhancing understanding about the role of identity can be helpful in treatment programs especially in harm reduction approaches. PMID:26234975

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

    ERIC Educational Resources Information Center

    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…

  14. Enhanced methamphetamine self-administration in a neurodevelopmental rat model of schizophrenia

    PubMed Central

    McCallum, Sarah E.; Glick, Stanley D.; O’Donnell, Patricio

    2008-01-01

    Rationale Substance abuse is more prevalent among patients with schizophrenia than in the general population. The considerable overlap in neurobiological disruptions thought to underlie each condition suggests that addictive behavior may represent a primary symptom of schizophrenia. Objective This study investigated drug-seeking in a neurodevelopmental animal model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model. Materials and methods At postnatal day 7, rats received an excitotoxic ventral hippocampus lesion or a sham procedure and were trained as adults to self-administer methamphetamine (0.1 mg/kg/infusion) or respond for natural reinforcement (water or food). Results NVHL rats were faster than shams to acquire the operant response for either drug self-administration or water reinforcement, suggesting that simple instrumental learning may be enhanced in these animals. NVHL and sham rats displayed no differences in fixed-ratio (FR) responding for either methamphetamine or food, and both groups of animals were equally sensitive to methamphetamine dose changes (0.05, 0.1, or 0.2 mg/kg/infusion). However, under a progressive-ratio (PR) schedule, NVHL animals reached significantly higher break points (NVHL 18 infusions; sham 12 infusions) for methamphetamine but not food reinforcement, suggesting enhanced motivation to acquire drug and/or elevated incentive value of the drug that did not generalize to another form of reinforcement. Conclusions These data indicate that developmental disruption of the hippocampus elevates rats’ vulnerability to drug-seeking behavior under PR conditions. Furthermore, drug self-administration in the NVHL animal emulates addictive behavior in schizophrenia, making this model useful for investigating the mechanisms of dual diagnosis, including the neurobiological and behavioral similarities between addiction and schizophrenia. PMID:18500636

  15. Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results

    PubMed Central

    Himes, Sarah K.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Smith, Lynne M.; Arria, Amelia M.; Grotta, Sheri A. Della; Dansereau, Lynne M.; Abar, Beau; Neal, Charles R.; Lester, Barry M.; Huestis, Marilyn A.

    2014-01-01

    Background The objective was to evaluate effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Methods Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child’s neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared to child hair results. Results A total of 264 children were evaluated. Significantly more PME children (n=133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n=131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared to PME children without postnatal exposure. Conclusions Child hair testing offered a non-invasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years

  16. Frequency of Methamphetamine Use as a Major Contributor Toward the Severity of Cardiomyopathy in Adults ≤50 Years.

    PubMed

    Neeki, Michael M; Kulczycki, Michael; Toy, Jake; Dong, Fanglong; Lee, Carol; Borger, Rodney; Adigopula, Sasikanth

    2016-08-15

    Methamphetamine is one of the most commonly abused illegal drugs in the United States. Health care providers are commonly faced with medical illness caused by methamphetamine. This study investigates the impact of methamphetamine use on the severity of cardiomyopathy and heart failure in young adults. This retrospective study analyzed patients seen at Arrowhead Regional Medical Center from 2008 to 2012. Patients were between 18 and 50 years old. All patients had a discharge diagnosis of cardiomyopathy or heart failure. The severity of disease was quantified by left ventricular systolic dysfunction: heart failure with preserved ejection fraction to mildly reduced if ejection fraction was >40% and moderate to severely depressed if ejection fraction was ≤40%. Methamphetamine abuse was determined by a positive urine drug screen or per documented history. Of the 590 patients, 223 (37.8%) had a history of methamphetamine use. More than half the population was men (n = 389, 62.3%); 41% was Hispanic (n = 243), 25.8% was Caucasian (n = 152), and 27.8% was African-American (n = 164); 60.9% were in the age range of 41 to 50 years (n = 359). Patients with a history of methamphetamine use had increased odds (odds ratio = 1.80, 95% confidence interval 1.27 to 2.57) of having a moderately or severely reduced ejection fraction. Additionally, men were more likely (odds ratio 3.13, 95% confidence interval 2.14 to 4.56) to have worse left ventricular systolic dysfunction. In conclusion, methamphetamine use was associated with an increased severity of cardiomyopathy in young adults. PMID:27374605

  17. Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: Link to impulsivity in methamphetamine users

    PubMed Central

    Kohno, Milky; Okita, Kyoji; Morales, Angelica M.; Robertson, Chelsea; Dean, Andy C.; Ghahremani, Dara G.; Sabb, Fred; Mandelkern, Mark A.; Bilder, Robert M.; London, Edythe D.

    2015-01-01

    Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC), and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between midbrain and striatum, orbitofrontal cortex, and insula in methamphetamine-dependent participants but a positive relationship in the control group. In Study 2, an interaction of group with RSFC on impulsivity was observed. Methamphetamine-dependent participants users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals. PMID:26830141

  18. Chronic variable stress and intravenous methamphetamine self-administration - Role of individual differences in behavioral and physiological reactivity to novelty.

    PubMed

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

    2016-09-01

    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

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

    PubMed Central

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

    2012-01-01

    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 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 (4 injections of 2.5 or 5.0 mg/kg at 2 hr 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 MDMA on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. Because 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. PMID:23205838

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

    PubMed

    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. PMID:23205838

  1. Respondent driven sampling is an effective method for engaging methamphetamine users in HIV prevention research in South Africa

    PubMed Central

    Kimani, Stephen M.; Watt, Melissa H.; Merli, M. Giovanna; Skinner, Donald; Myers, Bronwyn; Pieterse, Desiree; MacFarlane, Jessica C.; Meade, Christina S.

    2014-01-01

    Background South Africa, in the midst of the world’s largest HIV epidemic, has a growing methamphetamine problem. Respondent driven sampling (RDS) is a useful tool for recruiting hard-to-reach populations in HIV prevention research, but its use with methamphetamine smokers in South Africa has not been described. This study examined the effectiveness of RDS as a method for engaging methamphetamine users in a Cape Town township into HIV behavioral research. Methods Standard RDS procedures were used to recruit active methamphetamine smokers from a racially diverse peri-urban township in Cape Town. Effectiveness of RDS was determined by examining social network characteristics (network size, homophily, and equilibrium) of recruited participants. Results Beginning with 8 seeds, 345 methamphetamine users were enrolled over 6 months, with a coupon return rate of 67%. The sample included 197 men and 148 women who were racially diverse (73% Coloured, 27% Black African) and had a mean age of 28.8 years (SD=7.2). Social networks were adequate (mean network size >5) and mainly comprised of close social ties. Equilibrium on race was reached after 11 waves of recruitment, and after ≤3 waves for all other variables of interest. There was little to moderate preference for either in- or out-group recruiting in all subgroups. Conclusions Results suggest that RDS is an effective method for engaging methamphetamine users into HIV prevention research in South Africa. Additionally, RDS may be a useful strategy for seeking high-risk methamphetamine users for HIV testing and linkage to HIV care in this and other low resource settings. PMID:25128957

  2. Positive Affect and Processes of Recovery among Treatment-Seeking Methamphetamine Users

    PubMed Central

    Carrico, Adam W.; Woods, William J.; Siever, Michael D.; Discepola, Michael V.; Dilwort, Samantha E.; Neilands, Torsten B.; Miller, Nicole; Moskowitz, Judith Tedlie

    2015-01-01

    Background Revised Stress and Coping Theory proposes that positive affect serves adaptive functions, independent of negative affect. However, scant research has examined whether, how, and under what circumstances positive affect is associated with decreased substance use. Methods Eighty-eight methamphetamine-using men who have sex with men (MSM) completed the baseline assessment for substance abuse treatment outcome study which included measures of positive and negative affect, cognitive-behavioral change processes (i.e., approach-oriented coping, self-efficacy for managing methamphetamine triggers, and abstinence-related action tendencies), abstinence-specific social support, and self-reported substance use. Participants also provided a urine sample for toxicology screening. Results After controlling for demographic characteristics and negative affect, higher positive affect was independently associated with greater approach-oriented coping, abstinence-related action tendencies, and abstinence-specific social support. Positive affect was also independently associated with greater self-efficacy for managing methamphetamine triggers, but only at lower levels of negative affect. Through these cognitive-behavioral and social pathways, positive affect was indirectly associated with lower frequency of stimulant use in the past 30 days, lower odds of reporting stimulant use two or more days in a row, and lower odds of providing a urine sample that was reactive for stimulant metabolites. On the other hand, negative affect was not indirectly associated with any measure of stimulant use. Conclusions Clinical research is needed to examine the pathways whereby positive affect may predict better substance abuse treatment outcomes. PMID:23684632

  3. A comparison of methamphetamine-dependent inpatients childhood attention deficit hyperactivity disorder symptomatology.

    PubMed

    Jaffe, Craig; Bush, Kristen R; Straits-Troster, Kristy; Meredith, Charles; Romwall, Lisa; Rosenbaum, Gail; Cherrier, Monique; Saxon, Andrew J

    2005-01-01

    Methamphetamine-dependent inpatients (N = 51) were screened for childhood attention deficit hyperactivity disorder (ADHD) using the Wender Utah Rating Scale upon admission to 30-day inpatient treatment. Baseline assessments included neuropsychological tests of executive function, memory, information processing, verbal fluency, attention, motor skills, and the Brief Symptom Inventory (BSI), a measure of psychiatric symptomatology. The thirty-six participants (70.6%) screening positive for ADHD reported significantly more frequent methamphetamine use prior to baseline. Baseline cognitive functioning was similar between groups, but the presumptive ADHD participants exhibited significantly worse psychiatric symptomatology. At three-week follow- up, 41 participants (80.4%) repeated the neuropsychological battery and BSI. All 10 non-completers screened positive for ADHD. The entire sample improved with abstinence in most neuropsychological domains except memory. The presumptive ADHD group failed to improve on tests of attention. All participants demonstrated significant reductions in psychiatric symptoms with abstinence. Methamphetamine-dependent individuals with ADHD symptoms are common and pose a significant treatment challenge. PMID:16186089

  4. GLOBAL AND LOCAL MORPHOMETRIC DIFFERENCES IN RECENTLY ABSTINENT METHAMPHETAMINE-DEPENDENT INDIVIDUALS

    PubMed Central

    Schwartz, Daniel L.; Mitchell, Alex D.; Lahna, David L.; Luber, Hannah S.; Huckans, Marilyn S.; Mitchell, Suzanne H.; Hoffman, William F.

    2010-01-01

    Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to MA use history, length of abstinence and age of first use. Controls had greater density relative to MA in bilateral insula and left middle frontal gyrus. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 21) was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity. PMID:20096794

  5. Detection of methamphetamine and its main metabolite in fingermarks by liquid chromatography-mass spectrometry.

    PubMed

    Zhang, Ting; Chen, Xueguo; Yang, Ruiqin; Xu, Yingjian

    2015-03-01

    A sensitive and efficient method applying liquid chromatography-mass spectrometry for the analysis of methamphetamine and its main metabolite in fingermark deposits was described. Using this method, good linear relationship of methamphetamine was obtained in the range of 0.005μg to 0.5μg per cotton swab, the limit of detection was 1.5ng per cotton swab, the limit of quantitation was 5.0ng per cotton swab and the average values of recovery ratios were above 70.1%. Moreover, the influence factors for the detection of methamphetamine in fingermarks, such as kinds of substrates, development methods and extraction methods, were all discussed in details. The results showed that good recovery ratios could be obtained on painted wood and smooth substrates surfaces. Development methods in commercial powder could not influence the quality of examination of exogenous drug in latent fingermark. Furthermore, the results indicated that the method mentioned here could be applied in the analysis of forensic trace evidences and samples obtained in clinically addicted cases. PMID:25576675

  6. Patient Reactance Moderates the Effect of Directive Telephone Counseling for Methamphetamine Users

    PubMed Central

    Karno, Mitchell; Farabee, David; Brecht, Mary-Lynn; Rawson, Richard

    2012-01-01

    Objective: This study examined the impact of the interaction between patient reactance and treatment directiveness on the effectiveness of telephone aftercare for methamphetamine dependence. Method: Reactance was assessed at baseline, and participants were randomly assigned to directive or nondirective treatment conditions. Logistic regression tested for the significance of the interaction as a predictor of 3-month and 12-month use of methamphetamine and stimulants. Results: A significant interaction was observed at the 3-month follow-up, in which the directive condition was less effective for patients higher in reactance and was more effective for patients lower in reactance. Among patients at a high level of reactance, the nondirective condition increased the likelihood of abstinence. Conclusions: This study suggests that, in the context of telephone-based care, directive interventions offer short-term clinical benefit for methamphetamine users who readily accept influence from authority figures, whereas nondirective interventions offer benefit for patients who do not readily accept influence. The short-term nature of these effects indicates that there is a need for brief but ongoing telephone support to maintain treatment gains. PMID:22846250

  7. Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 Caenorhabditis elegans.

    PubMed

    Katner, Simon N; Neal-Beliveau, Bethany S; Engleman, Eric A

    2016-01-01

    Methamphetamine (MAP) addiction is substantially prevalent in today's society, resulting in thousands of deaths and costing billions of dollars annually. Despite the potential deleterious consequences, few studies have examined the long-term effects of embryonic MAP exposure. Using the invertebrate nematode Caenorhabditis elegans allows for a controlled analysis of behavioral and neurochemical changes due to early developmental drug exposure. The objective of the current study was to determine the long-term behavioral and neurochemical effects of embryonic exposure to MAP in C. elegans. In addition, we sought to improve our conditioning and testing procedures by utilizing liquid filtration, as opposed to agar, and smaller, 6-well testing plates to increase throughput. Wild-type N2 C. elegans were embryonically exposed to 50 μM MAP. Using classical conditioning, adult-stage C. elegans were conditioned to MAP (17 and 500 μM) in the presence of either sodium ions (Na+) or chloride ions (Cl-) as conditioned stimuli (CS+/CS-). Following conditioning, a preference test was performed by placing worms in 6-well test plates spotted with the CS+ and CS- at opposite ends of each well. A preference index was determined by counting the number of worms in the CS+ target zone divided by the total number of worms in the CS+ and CS- target zones. A food conditioning experiment was also performed in order to determine whether embryonic MAP exposure affected food conditioning behavior. For the neurochemical experiments, adult worms that were embryonically exposed to MAP were analyzed for dopamine (DA) content using high-performance liquid chromatography. The liquid filtration conditioning procedure employed here in combination with the use of 6-well test plates significantly decreased the time required to perform these experiments and ultimately increased throughput. The MAP conditioning data found that pairing an ion with MAP at 17 or 500 μM significantly increased the preference

  8. Enhanced performance of methamphetamine lateral flow cassettes using an electronic lateral flow reader

    PubMed Central

    Smith, Jerome P.; Sammons, Deborah L.; Robertson, Shirley A.; Snawder, John E.

    2015-01-01

    Surface contamination from methamphetamine in meth labs continues to be a problem. We had previously developed a lateral flow assay cassette for field detection of methamphetamine contamination that is commercially available and has been used by a number of groups to assess contamination. This cassette uses the complete disappearance of the test line as an end point for detection of 50 ng/100 cm2 of methamphetamine contamination for surface sampling with cotton swabs. In the present study, we further evaluate the response of the cassettes using an electronic lateral flow reader to measure the intensities of the test and control lines. The cassettes were capable of detecting 0.25 ng/ml for calibration solutions. For 100 cm2 ceramic tiles that were spiked with methamphetamine and wiped with cotton tipped wooden swabs wetted in assay/sampling buffer, 1 ng/tile was detected using the reader. Semi-quantitative results can be produced over the range 0–10 ng/ml for calibration solutions and 0–25 ng/tile for spiked tiles using either a 4-parameter logistic fit of test line intensity versus concentration or spiked mass or the ratio of the control line to the test line intensity fit to concentration or spiked mass. Recovery from the tiles was determined to be about 30% using the fitted curves. Comparison of the control line to the test line was also examined as a possible visual detection end point and it was found that the control line became more intense than the test line at 0.5 to 1 ng/ml for calibration solutions or 1 to 2 ng/tile for spiked tiles. Thus the lateral flow cassettes for methamphetamine have the potential to produce more sensitive semi-quantitative results if an electronic lateral flow reader is used and can be more sensitive for detection if the comparison of the control line to the test line is used as the visual end point. PMID:25379615

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

    ERIC Educational Resources Information Center

    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…

  10. Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.

    PubMed

    Shen, Ying-Ling; Chen, Shao-Tsu; Chan, Tzu-Yi; Hung, Tsai-Wei; Tao, Pao-Luh; Liao, Ruey-Ming; Chan, Ming-Huan; Chen, Hwei-Hsien

    2016-02-01

    Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use. PMID:26743042

  11. Effects of neonatal (+)-methamphetamine on path integration and spatial learning in rats: effects of dose and rearing conditions.

    PubMed

    Vorhees, Charles V; Herring, Nicole R; Schaefer, Tori L; Grace, Curtis E; Skelton, Matthew R; Johnson, Holly L; Williams, Michael T

    2008-10-01

    Postnatal day (P)11-20 (+)-methamphetamine (MA) treatment impairs spatial learning and reference memory in the Morris water maze, but has marginal effects on learning in a labyrinthine maze. A subsequent experiment showed that MA treatment on P11-15, but not P16-20, is sufficient to induce Morris maze deficits. Here we tested the effects of P11-15 MA treatment under two different rearing conditions on Morris maze performance and path integration learning in the Cincinnati water maze in which distal cues were unavailable by using infrared illumination. Littermates were treated with 0, 10, 15, 20, or 25mg/kg MA x 4/day (2 h intervals). Half the litters were reared under standard housing conditions and half under partial enrichment by adding stainless steel enclosures. All MA groups showed impaired Cincinnati water maze performance with no significant effects of rearing condition. In the Morris maze, the MA-25 group showed impaired spatial acquisition, reversal, and small platform learning. Enrichment significantly improved Morris maze acquisition in all groups but did not interact with treatment. The male MA-25 group was also impaired on probe trial performance after acquisition and on small platform trials. A narrow window of MA treatment (P11-15) induces impaired path integration learning irrespective of dose within the range tested but impairments in spatial learning are dependent on dose. The results demonstrate that a narrower exposure window (5 days) changes the long-term effects of MA treatment compared to longer exposures (10 days). PMID:18502078

  12. Hair analysis for drugs of abuse. VI. The excretion of methoxyphenamine and methamphetamine into beards of human subjects.

    PubMed

    Nakahara, Y; Takahashi, K; Konuma, K

    1993-12-01

    The excretion of methoxyphenamine (MOP) and methamphetamine (MA) into beards has been studied. Six healthy male subjects orally took 50 mg of MOP at a single dose and 7 doses for a successive 7 days. Their beard hairs were collected by an electric shaver every morning until MOP disappeared from the beard. After washing with 0.1% SDS, the beard samples were extracted with methanol-5 N HCl (20:1) under ultra-sonication for 1 h and the solution was kept overnight. MOP in the extract was determined by GC/MS using deuterium labelled MOP as an internal standard after trifluoroacetyl-derivatization. The drug concentrations in beard and the reproducibility of analysis were compared with the three procedures, unwashed, 0.1% SDS (wash I) and the additional ethanol (wash II) wash. The drug concentration in beard after SDS wash was 0.5-2.5 ng/mg lower than that in unwashed beard during the first 5-6 days. The drug concentration in beard after ethanol wash was much lower than that in the unwashed beard. The drug excreted into beard was detected 10 approximately 12 days for a single dose and 12-14 days for 7 doses after the last dosage at the cut off level of 1 ng/mg. On the contrary, the drug excreted in urine was not detected after more than 3 days after use. O-Desmethyl MOP, a major metabolite of MOP, was also detected in beard. The procedures were applied to the detection of MA in beard of MA abusers. It was realized that a beard sample was more useful than a urine sample assuming a longer detection. PMID:7908007

  13. Effects of neonatal (+)-methamphetamine on path integration and spatial learning in rats: Effects of dose and rearing conditions

    PubMed Central

    Vorhees, Charles V.; Herring, Nicole R.; Schaefer, Tori L.; Grace, Curtis E.; Skelton, Matthew R.; Johnson, Holly L.; Williams, Michael T.

    2008-01-01

    Postnatal day (P)11–20 (+)-methamphetamine (MA) treatment impairs spatial learning and reference memory in the Morris water maze, but has marginal effects on path integration learning in a labyrinthine maze. A subsequent experiment showed that MA treatment on P11–15, but not P16–20, is sufficient to induce Morris maze deficits. Here we tested the effects of P11–15 MA treatment under two different rearing conditions on Morris maze performance and path integration learning in the Cincinnati water maze in which distal cues were unavailable by using infrared illumination. Littermates were treated with 0, 10, 15, 20, or 25 mg/kg x 4 per day (2 h intervals). Half the litters were reared under standard housing conditions and half under partial enrichment by adding stainless steel enclosures. All MA groups showed impaired Cincinnati water maze performance with no significant effects of rearing condition. In the Morris maze, the MA-25 group showed impaired spatial acquisition, reversal, and small platform learning. Enrichment significantly improved Morris maze acquisition in all groups but did not interact with treatment. The male MA-25 group was also impaired on probe trial performance after acquisition and on small platform trials. A narrow window of MA treatment (P11–15) induces impaired path integration learning irrespective of dose within the range tested but impairments in spatial learning are dependent on dose. The results demonstrate that a narrower exposure window (5 days) changes the long-term effects of MA treatment compared to longer exposures (10 days). PMID:18502078

  14. A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments

    PubMed Central

    Nanaware-Kharade, Nisha; Thakkar, Shraddha; Gonzalez III, Guillermo A.; Peterson, Eric C.

    2015-01-01

    To address the need for effective medications to aid in the treatment of methamphetamine (METH) abuse, we used a nanotechnology approach to customize the in vivo behavior of an anti-METH single chain antibody (scFv7F9Cys). Anti-METH scFv7F9Cys was conjugated to dendrimer nanoparticles via a polyethylene glycol (PEG) linker to generate high-order conjugates termed dendribodies. We found that the high affinity (KD = 6.2 nM) and specificity for METH was unchanged after nanoparticle conjugation. The dendribodies were administered in an i.v. bolus to male Sprague Dawley rats after starting a s.c. infusion of METH. The PCKN values for clearance and volume of distribution of scFv7F9Cys after conjugation to dendrimers decreased 45 and 1.6-fold respectively, and the terminal elimination half-life increased 20-fold. Organ distribution of scFv7F9Cys and dendribody in blood and urine agreed well with the PCKN data. Renal clearance appeared to be the major route of elimination for both experimental medications. We have thus successfully developed a novel multivalent METH-binding nanomedicine by conjugating multiple anti-METH scFvs to dendrimer nanoparticles, extending the scFv half-life from 1.3 (±0.3) to 26 (±2.6) hr. These data suggest that the dendribody design could be a feasible platform for generating multivalent antibodies with customizable PCKN profiles. PMID:26159352

  15. A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments.

    PubMed

    Nanaware-Kharade, Nisha; Thakkar, Shraddha; Gonzalez, Guillermo A; Peterson, Eric C

    2015-01-01

    To address the need for effective medications to aid in the treatment of methamphetamine (METH) abuse, we used a nanotechnology approach to customize the in vivo behavior of an anti-METH single chain antibody (scFv7F9Cys). Anti-METH scFv7F9Cys was conjugated to dendrimer nanoparticles via a polyethylene glycol (PEG) linker to generate high-order conjugates termed dendribodies. We found that the high affinity (KD = 6.2 nM) and specificity for METH was unchanged after nanoparticle conjugation. The dendribodies were administered in an i.v. bolus to male Sprague Dawley rats after starting a s.c. infusion of METH. The PCKN values for clearance and volume of distribution of scFv7F9Cys after conjugation to dendrimers decreased 45 and 1.6-fold respectively, and the terminal elimination half-life increased 20-fold. Organ distribution of scFv7F9Cys and dendribody in blood and urine agreed well with the PCKN data. Renal clearance appeared to be the major route of elimination for both experimental medications. We have thus successfully developed a novel multivalent METH-binding nanomedicine by conjugating multiple anti-METH scFvs to dendrimer nanoparticles, extending the scFv half-life from 1.3 (± 0.3) to 26 (± 2.6) hr. These data suggest that the dendribody design could be a feasible platform for generating multivalent antibodies with customizable PCKN profiles. PMID:26159352

  16. Sensitization to the motor stimulant effects of 3,4-methylenedioxypyrovalerone (MDPV) and cross-sensitization to methamphetamine in rats

    PubMed Central

    Taylor, Sara B.; Nemirovsky, Natali E.; Olive, M. Foster

    2016-01-01

    Background In recent years, there has been a dramatic increase in abuse of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV), often in combination with other illicit stimulants. Purpose We sought to determine if repeated exposure to MDPV would produce sensitization to the motor stimulant effects of the drug, and whether cross-sensitization would develop with the stimulant effects of methamphetamine (METH). Study design Male Sprague-Dawley rats were administered MDPV (1 or 5 mg/kg) or saline once daily for 5 days at 24 hour intervals, or were administered MDPV (1 mg/kg) or saline once daily for 5 days at 48 hour intervals. For cross-sensitization experiments, rats were administered METH (1 mg/kg) or MDPV (1 or 5 mg/kg) once daily for 5 days at 48 hour intervals, and following a 5 day incubation period, were given an acute challenge injection of either MDPV (0.5 mg/kg) or METH (0.5 mg/kg), respectively. Results Rats repeatedly administered MDPV (1 mg/kg) every 48 hours, but not every 24 hours, demonstrated increased motor activity when given either a subsequent challenge of MDPV (0.5 mg/kg i.p.) or METH (0.5 mg/kg), indicating the development of behavioral sensitization and cross-sensitization, respectively. Moreover, rats repeatedly administered METH (1 mg/kg) every 48 hours did not exhibit cross-sensitization to the motor stimulating effects of a subsequent challenge with MDPV (0.5 mg/kg). Conclusion These results suggest that specific patterns of MDPV administration may lead to lasting changes in behavioral responses to subsequent METH exposure. PMID:27284493

  17. BDNF–TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms

    PubMed Central

    Ren, Q; Ma, M; Yang, C; Zhang, J-C; Yao, W; Hashimoto, K

    2015-01-01

    Depression is a core symptom of methamphetamine (METH) withdrawal during the first several weeks of abstinence. However, the precise mechanisms underlying METH withdrawal symptoms remain unknown. Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), have a role the in pathophysiology of depression. In this study, we examined the role of BDNF–TrkB signaling in different brain regions of male mice with METH withdrawal symptoms. Repeated METH (3 mg kg−1 per day for 5 days) administration to mice caused a long-lasting depression-like behavior including anhedonia. Western blot analysis showed that BDNF levels in the nucleus accumbens (NAc) of METH-treated mice were significantly higher than those of control mice whereas BDNF levels in other regions, including the prefrontal cortex and hippocampus, were not altered. METH-induced depression-like behavior, behavioral sensitization and dendritic changes in the NAc shell were improved by subsequent subchronic administration of TrkB antagonist ANA-12 (0.5 mg kg−1 per day for 14 days), but not TrkB agonist 7,8-dihydroxyflavone (10 mg kg−1 per day for 14 days). In vivo microdialysis showed that METH (1 mg kg−1)-induced dopamine release in NAc shell of METH-treated mice was attenuated after subsequent subchronic ANA-12 administration. Interestingly, a single bilateral infusion of ANA-12 into the NAc shell, but not NAc core, showed a rapid and long-lasting therapeutic effect. However, ketamine and paroxetine had no effect. These findings suggest that increased BDNF–TrkB signaling in the NAc shell has an important role in the behavioral abnormalities after withdrawal from repeated METH administration, and that TrkB antagonists are potential therapeutic drugs for withdrawal symptoms in METH abusers. PMID:26506052

  18. Effects of Family-Centered Empowerment Model Based Education Program on Quality of Life in Methamphetamine Users and Their Families

    PubMed Central

    Ghasemi, Afsaneh; Rahimi Foroshani, Abbass; Kheibar, Nasrin; Latifi, Marziye; Khanjani, Narges; Eshagh Afkari, Mohammad; Taghdisi, Mohammad Hossein; Ghasemi, Faranak; Shojaeizadeh, Davoud; Dastoorpour, Maryam

    2014-01-01

    Background: Nowadays there are more concerns about drug treatment of methamphetamine abusers whereas quality of life (QOL) related supportive psychotherapy is less credited. Objectives: This study aimed to evaluate the effects of family-centered empowerment model on social support and QOL of methamphetamine users and their families. Patients and Methods: This study was a randomized clinical trial; individuals were randomly allocated to three groups: a group for educating methamphetamine users in recovery (95 subjects), a group for educating a family member of methamphetamine users in recovery (95 subjects) and a control group (95 subjects). Data collecting instruments were standard questionnaires of social support and health-related quality of life (HRQOL). Data were analyzed using χ2-test, t-test, paired t-test, Pearson’s correlation and ANOVA. Results: Mean scores of QOL and social support dimensions changed significantly in two intervention groups (P < 0.0001), but didn’t change in the control group (P > 0.05). Also, there was a positive significant relation (P < 0.05) between total social support and all dimensions of QOL for all study groups. Conclusions: Family-centered empowerment model, easily adapted to methamphetamine users and their families, leads to improved social supports and QOL. PMID:24829765

  19. Male contraception.

    PubMed

    Chao, Jing; Page, Stephanie T; Anderson, Richard A

    2014-08-01

    Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the non-hormonal approach is based on identifying specific processes in sperm development, maturation and function. A range of targets has been identified in animal models, and targeted effectively. This approach, however, remains in the pre-clinical domain at present. There are, therefore, grounds for considering that safe, effective and reversible methods of contraception for men can be developed. PMID:24947599

  20. Male contraception

    PubMed Central

    Chao, Jing; Page, Stephanie T.; Anderson, Richard A.

    2015-01-01

    Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the nonhormonal approach is based on identifying specific processes in sperm development, maturation and function. A range of targets has been identified in animal models, and targeted effectively. This approach, however, remains in the pre-clinical domain at present. There are, therefore, grounds for considering that safe, effective and reversible methods of contraception for men can be developed. PMID:24947599

  1. Detection of Methamphetamine and Morphine in Urine and Saliva Using Excitation-Emission Matrix Fluorescence and a Second-Order Calibration Algorithm

    NASA Astrophysics Data System (ADS)

    Xu, B. Y.; Ye, Y.; Liao, L. C.

    2016-07-01

    A new method was developed to determine the methamphetamine and morphine concentrations in urine and saliva based on excitation-emission matrix fluorescence coupled to a second-order calibration algorithm. In the case of single-drug abuse, the results showed that the average recoveries of methamphetamine and morphine were 95.3 and 96.7% in urine samples, respectively, and 98.1 and 106.2% in saliva samples, respectively. The relative errors were all below 5%. The simultaneous determination of methamphetamine and morphine in urine using two second-order algorithms was also investigated. Satisfactory results were obtained with a self-weighted alternating trilinear decomposition algorithm. The root-mean-square errors of the predictions were 0.540 and 0.0382 μg/mL for methamphetamine and morphine, respectively. The limits of detection of the proposed methods were very low and sufficient for studying methamphetamine and morphine in urine.

  2. Vehicle-Mounted Portable Mass Spectrometry System for the Covert Detection via Spatial Analysis of Clandestine Methamphetamine Laboratories.

    PubMed

    Mach, Phillip M; McBride, Ethan M; Sasiene, Zachary J; Brigance, Katie R; Kennard, Shelia K; Wright, Kenneth C; Verbeck, Guido F

    2015-11-17

    The ability to detect atmospheric effluent from clandestine methamphetamine manufacture is a useful tool for law enforcement. A membrane inlet mass spectrometer is mounted onto an all-electric drive capable hybrid vehicle that samples the atmosphere while in motion. Attributing a latitude and longitude to each spectrum collected, unique chemical fingerprints from clandestine manufacture are then mapped. This location-based mass spectrum data provides a localization to an area of interest. The synthesis of methamphetamine precursors was performed, and the impurities from such reactions were observed. A mock manufacture was setup, and the impurities were introduced into the atmosphere via heating. The detection of products and impurities using this mobile platform has shown the effectiveness of locating and localizing the manufacture of methamphetamine. PMID:26457561

  3. A pilot study investigating the effects of trauma, experiential avoidance, and disease management in HIV-positive MSM using methamphetamine.

    PubMed

    Chartier, Maggie; Vinatieri, Trisha; Delonga, Kathryn; McGlynn, Lawrence M; Gore-Felton, Cheryl; Koopman, Cheryl

    2010-01-01

    With high rates of trauma among HIV-positive men who have sex with men (MSM) who use methamphetamine, this preliminary pilot study examined the associations between experiential avoidance, trauma symptoms, and management of a chronic illness. Among a small sample of HIV-positive, methamphetamine-using MSM in a California Bay Area County, greater reported experiential avoidance was significantly related to greater reported trauma and symptoms of traumatic stress. Furthermore, greater reported experiential avoidance was significantly related to reduced self-efficacy of illness management and more frequent methamphetamine use. Although further research is needed, these data suggest that addressing issues of experiential avoidance and trauma could affect behavioral choices and treatment outcomes in this high-risk population. PMID:20142604

  4. Temporal relations between methamphetamine use and HIV seroconversion in gay, bisexual, and other men who have sex with men.

    PubMed

    Halkitis, Perry N; Levy, Michael D; Solomon, Todd M

    2016-01-01

    Data from a cross-sectional study of gay, bisexual, and other men who have sex with men who were active methamphetamine users were analyzed to assess temporal relations between HIV seroconversion and initiation of methamphetamine use. Of the 100 men, 58 reported being HIV-positive. Most HIV-positive participants (65%) initiated methamphetamine use after seroconverting. Among those who initiated use before seroconversion, 8 years elapsed between onset of use and time of infection. Findings suggest the need to develop nuanced and targeted interventions aimed at disentangling the "meth-sex" link in this population. Findings also suggest use of the drug as a coping mechanism for those living with HIV. PMID:24578373

  5. Developmental and behavioral consequences of prenatal methamphetamine exposure: a review of the Infant Development, Environment, and Lifestyle (IDEAL) Study

    PubMed Central

    Smith, Lynne M.; Diaz, Sabrina; LaGasse, Linda L.; Wouldes, Trecia; Derauf, Chris; Newman, Elana; Arria, Amelia; Huestis, Marilyn A.; Haning, William; Strauss, Arthur; Grotta, Sheri Della; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

    2015-01-01

    This study reviews the findings from the Infant Development, Environment, and Lifestyle Study (IDEAL), a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior. PMID:26212684

  6. Developmental and behavioral consequences of prenatal methamphetamine exposure: A review of the Infant Development, Environment, and Lifestyle (IDEAL) study.

    PubMed

    Smith, Lynne M; Diaz, Sabrina; LaGasse, Linda L; Wouldes, Trecia; Derauf, Chris; Newman, Elana; Arria, Amelia; Huestis, Marilyn A; Haning, William; Strauss, Arthur; Della Grotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

    2015-01-01

    This study reviews the findings from the Infant Development, Environment, and Lifestyle (IDEAL) study, a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior. PMID:26212684

  7. A dysphoric-like state during early withdrawal from extended access to methamphetamine self-administration in rats

    PubMed Central

    Jang, Choon-Gon; Whitfield, Timothy; Schulteis, Gery; Koob, George F.; Wee, Sunmee

    2012-01-01

    Rationale Negative emotional states during drug withdrawal may contribute to compulsive drug intake and seeking in humans. Studies suggest that extended access to methamphetamine induces compulsive drug intake in rats. Objective The present study tested the hypothesis that compulsive methamphetamine intake in rats with extended access is associated with negative emotional states during drug withdrawal. Methods Rats with short (1 h, ShA) and extended access (6 h, LgA) to methamphetamine self-administration (0.05 mg/kg/infusion) were tested for reward thresholds using intracranial self-stimulation (ICSS). Different groups of ShA and LgA rats were examined for depression-like and anxiety-like states in the novelty-suppressed feeding, open field, defensive burying, and forced swim tests. Results With extended access, ICSS thresholds gradually increased, which was correlated with the increase of drug intake. During drug withdrawal, the increased ICSS thresholds returned to levels observed before exposure to extended access to methamphetamine. Upon re-exposure to extended access to methamphetamine, ICSS thresholds showed a more rapid escalation than during the initial exposure. LgA rats showed a longer latency to approach chow in the center of a novel field and remained immobile longer in the forced swim test than ShA rats did during early withdrawal. In contrast, ShA rats actively buried an aversive shock probe whereas LgA rats remained immobile in the defensive burying test. Conclusion The data suggest that extended access to methamphetamine produces a more depressive-like state than anxiety-like state in rats during early withdrawal. PMID:23007601

  8. A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Perez, Audrey Y.; Haney, Margaret; Foltin, Richard W.

    2015-01-01

    Rationale Despite their chemical similarities, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) produce differing neurochemical and behavioral responses in animals. In humans, individual studies of methamphetamine and MDMA indicate that the drugs engender overlapping and divergent effects; there are only limited data comparing the two drugs in the same individuals. Objectives This study examined the effects of methamphetamine and MDMA using a within-subject design. Methods Eleven adult volunteers completed this 13-day residential laboratory study, which consisted of four 3-day blocks of sessions. On the first day of each block, participants received oral methamphetamine (20, 40 mg), MDMA (100 mg), or placebo. Drug plasma concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and after. Food intake and sleep were also assessed. On subsequent days of each block, placebo was administered and residual effects were assessed. Results Acutely, both drugs increased cardiovascular measures and “positive” subjective effects and decreased food intake. In addition, when asked to identify each drug, participants had difficulty distinguishing between the amphetamines. The drugs also produced divergent effects: methamphetamine improved performance and disrupted sleep, while MDMA increased “negative” subjective-effect ratings. Few residual drug effects were noted for either drug. Conclusions It is possible that the differences observed could explain the differential public perception and abuse potential associated with these amphetamines. Alternatively, the route of administration by which the drugs are used recreationally might account for the many of the effects attributed to these drugs (i.e., MDMA is primarily used orally, whereas methamphetamine is used by routes associated with higher abuse potential). PMID:21713605

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

    PubMed Central

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

    1993-01-01

    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.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8467354

  10. Effects of combined treatment with mephedrone and methamphetamine or 3,4-methylenedioxymethamphetamine on serotonin nerve endings of the hippocampus

    PubMed Central

    Angoa-Pérez, Mariana; Kane, Michael J.; Herrera-Mundo, Nieves; Francescutti, Dina M.; Kuhn, Donald M.

    2013-01-01

    Aims Mephedrone is a stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Although mephedrone does not damage dopamine nerve endings it increases the neurotoxicity of amphetamine, methamphetamine and MDMA. The effects of mephedrone on serotonin (5HT) nerve endings are not fully understood, with some investigators reporting damage while others conclude it does not. Presently, we investigate if mephedrone given alone or with methamphetamine or MDMA damages 5HT nerve endings of the hippocampus. Main methods The status of 5HT nerve endings in hippocampus of female C57BL mice was assessed through measures of 5HT by HPLC and by immunoblot analysis of serotonin transporter (SERT) and tryptophan hydroxylase 2 (TPH2), selective markers of 5HT nerve endings. Astrocytosis was assessed through measures of glial fibrillary acidic protein (GFAP) (immunoblotting) and microglial activation was determined by histochemical staining with Isolectin B4. Key findings Mephedrone alone did not cause persistent reductions in the levels of 5HT, SERT or TPH2. Methamphetamine and MDMA alone caused mild reductions in 5HT but did not change SERT and TPH2 levels. Combined treatment with mephedrone and methamphetamine or MDMA did not change the status of 5HT nerve endings to an extent that was different from either drug alone. Significance Mephedrone does not cause toxicity to 5HT nerve endings of the hippocampus. When co-administered with methamphetamine or MDMA, drugs that are often co-abused with mephedrone by humans, toxicity is not increased as is the case for dopamine nerve endings when these drugs are taken together. PMID:23892197

  11. Structural Characterization of a Therapeutic Anti-Methamphetamine Antibody Fragment: Oligomerization and Binding of Active Metabolites

    PubMed Central

    Gokulan, Kuppan; Varughese, Kottayil I.

    2013-01-01

    Vaccines and monoclonal antibodies (mAb) for treatment of (+)-methamphetamine (METH) abuse are in late stage preclinical and early clinical trial phases, respectively. These immunotherapies work as pharmacokinetic antagonists, sequestering METH and its metabolites away from sites of action in the brain and reduce the rewarding and toxic effects of the drug. A key aspect of these immunotherapy strategies is the understanding of the subtle molecular interactions important for generating antibodies with high affinity and specificity for METH. We previously determined crystal structures of a high affinity anti-METH therapeutic single chain antibody fragment (scFv6H4, KD = 10 nM) in complex with METH and the (+) stereoisomer of 3,4-methylenedioxymethamphetamine (MDMA, or “ecstasy”). Here we report the crystal structure of scFv6H4 in homo-trimeric unbound (apo) form (2.60Å), as well as monomeric forms in complex with two active metabolites; (+)-amphetamine (AMP, 2.38Å) and (+)-4-hydroxy methamphetamine (p-OH-METH, 2.33Å). The apo structure forms a trimer in the crystal lattice and it results in the formation of an intermolecular composite beta-sheet with a three-fold symmetry. We were also able to structurally characterize the coordination of the His-tags with Ni2+. Two of the histidine residues of each C-terminal His-tag interact with Ni2+ in an octahedral geometry. In the apo state the CDR loops of scFv6H4 form an open conformation of the binding pocket. Upon ligand binding, the CDR loops adopt a closed formation, encasing the drug almost completely. The structural information reported here elucidates key molecular interactions important in anti-methamphetamine abuse immunotherapy. PMID:24349338

  12. Sustained-Release Methylphenidate in a Randomized Trial of Treatment of Methamphetamine Use Disorder

    PubMed Central

    Ling, Walter; Chang, Linda; Hillhouse, Maureen; Ang, Alfonso; Striebel, Joan; Jenkins, Jessica; Hernandez, Jasmin; Olaer, Mary; Mooney, Larissa; Reed, Susan; Fukaya, Erin; Kogachi, Shannon; Alicata, Daniel; Holmes, Nataliya; Esagoff, Asher

    2014-01-01

    Background and aims No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioural support and motivational incentives. Design This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT), and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. Setting Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. Participants 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20). Measurements The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events, and treatment satisfaction. Findings No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (p=0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (p=0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events, and treatment satisfaction. Conclusions Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioural support for moderate to severe methamphetamine use disorder but this requires confirmation. PMID:24825486

  13. Antagonism of Metabotropic Glutamate 1 Receptors Attenuates Behavioral Effects of Cocaine and Methamphetamine in Squirrel Monkeys

    PubMed Central

    Platt, Donna M.; Spealman, Roger D.

    2012-01-01

    Within the group I family of metabotropic glutamate receptors (mGluRs), substantial evidence points to a role for mGluR5 mechanisms in cocaine's abuse-related behavioral effects, but less is understood about the contribution of mGluR1, which also belongs to the group I mGluR family. The selective mGluR1 antagonist JNJ16259685 [(3,4-dihydro-2H-pyrano-[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone] was used to investigate the role of mGluR1 in the behavioral effects of cocaine and methamphetamine. In drug discrimination experiments, squirrel monkeys were trained to discriminate cocaine from saline by using a two-lever, food-reinforced operant procedure. JNJ16259685 (0.56 mg/kg) pretreatments significantly attenuated cocaine's discriminative stimulus effects and the cocaine-like discriminative stimulus effects of methamphetamine. In monkeys trained to self-administer cocaine or methamphetamine under a second-order schedule of intravenous drug injection, JNJ16259685 (0.56 mg/kg) significantly reduced drug-reinforced responding, resulting in a downward displacement of dose-response functions. In reinstatement studies, intravenous priming with cocaine accompanied by restoration of a cocaine-paired stimulus reinstated extinguished cocaine-seeking behavior, which was significantly attenuated by JNJ16259685 (0.56 mg/kg). Finally, in experiments involving food rather than drug self-administration, cocaine and methamphetamine increased the rate of responding, and the rate-increasing effects of both psychostimulants were significantly attenuated by JNJ16259685 (0.3 mg/kg). At the doses tested, JNJ16259685 did not significantly suppress food-reinforced behavior (drug discrimination or fixed-interval schedule of food delivery), but did significantly reduce species-typical locomotor activity in observational studies. To the extent that the psychostimulant-antagonist effects of JNJ16259685 are independent of motor function suppression, further research is warranted to

  14. Antagonism of metabotropic glutamate 1 receptors attenuates behavioral effects of cocaine and methamphetamine in squirrel monkeys.

    PubMed

    Achat-Mendes, Cindy; Platt, Donna M; Spealman, Roger D

    2012-10-01

    Within the group I family of metabotropic glutamate receptors (mGluRs), substantial evidence points to a role for mGluR5 mechanisms in cocaine's abuse-related behavioral effects, but less is understood about the contribution of mGluR1, which also belongs to the group I mGluR family. The selective mGluR1 antagonist JNJ16259685 [(3,4-dihydro-2H-pyrano-[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone] was used to investigate the role of mGluR1 in the behavioral effects of cocaine and methamphetamine. In drug discrimination experiments, squirrel monkeys were trained to discriminate cocaine from saline by using a two-lever, food-reinforced operant procedure. JNJ16259685 (0.56 mg/kg) pretreatments significantly attenuated cocaine's discriminative stimulus effects and the cocaine-like discriminative stimulus effects of methamphetamine. In monkeys trained to self-administer cocaine or methamphetamine under a second-order schedule of intravenous drug injection, JNJ16259685 (0.56 mg/kg) significantly reduced drug-reinforced responding, resulting in a downward displacement of dose-response functions. In reinstatement studies, intravenous priming with cocaine accompanied by restoration of a cocaine-paired stimulus reinstated extinguished cocaine-seeking behavior, which was significantly attenuated by JNJ16259685 (0.56 mg/kg). Finally, in experiments involving food rather than drug self-administration, cocaine and methamphetamine increased the rate of responding, and the rate-increasing effects of both psychostimulants were significantly attenuated by JNJ16259685 (0.3 mg/kg). At the doses tested, JNJ16259685 did not significantly suppress food-reinforced behavior (drug discrimination or fixed-interval schedule of food delivery), but did significantly reduce species-typical locomotor activity in observational studies. To the extent that the psychostimulant-antagonist effects of JNJ16259685 are independent of motor function suppression, further research is warranted to

  15. 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

    PubMed Central

    Moore, David J.; Montoya, Jessica L.; Blackstone, Kaitlin; Depp, Colin A.; Atkinson, J. Hampton; TMARC Group, The

    2013-01-01

    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. PMID:24078868

  16. Relationship between methamphetamine-induced dopamine release, hyperthermia, self-injurious behaviour and long term dopamine depletion in BALB/c and C57BL/6 mice.

    PubMed

    Halladay, Alycia K; Kusnecov, Alexander; Michna, Lauri; Kita, Taizo; Hara, Chiaki; Wagner, George C

    2003-07-01

    Differential sensitivity to neurotoxic effects of methamphetamine on striatal dopaminergic neurones between C57BL/6 and BALB/c mice has been established. In the present studies, the interaction of methamphetamine-induced dopamine release, self-injurious behaviour, the neural immune response, and the long-term (3 day) dopamine depletion were examined in these strains after administration of 8 mg/kg methamphetamine. BALB/c mice showed increased hyperthermia compared to the C57BL/6 strain, as well as induction of interleukin-1beta. Additionally, homovanillic acid (HVA) levels, as well as HVA/DA turnover ratios were elevated in the striatum and frontal cortex of BALB/c mice, both compared to untreated mice and to the C57BL/6 strain after a single injection of methamphetamine. Pretreatment with acetaminophen eliminated the methamphetamine-induced hyperthermia in BALB/c mice and reduced body temperature in C57BL/6 mice. However, acetaminophen pretreatment did not affect any parameters of dopaminergic toxicity in the striatum or frontal cortex of the BALB/c strain following repeated methamphetamine injections. Furthermore, acetaminophen pretreatment did not alter the incidence of self-injurious behaviour in BALB/c mice. Therefore, hyperthermia and methamphetamine-induced toxicity appear to be independent phenomena while self-injurious behaviour may provide a better predictor of toxicity, which, in turn, may be related to dopamine release. PMID:12828572

  17. 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.

    PubMed

    Moore, David J; Montoya, Jessica L; Blackstone, Kaitlin; Rooney, Alexandra; Gouaux, Ben; Georges, Shereen; Depp, Colin A; Atkinson, J Hampton; Tmarc Group, The

    2013-01-01

    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. PMID:24078868

  18. The use of δ13C isotope ratio mass spectrometry for methamphetamine profiling: comparison of ephedrine and pseudoephedrine-based samples to P2P-based samples.

    PubMed

    Toske, Steven G; Morello, David R; Berger, Jennifer M; Vazquez, Etienne R

    2014-01-01

    Differentiating methamphetamine samples produced from ephedrine and pseudoephedrine from phenyl-2-propanone precursors is critical for assigning synthetic route information for methamphetamine profiling. The use of isotope ratio mass spectrometry data is now a key component for tracking precursor information. Recent carbon (δ(13)C) isotope results from the analysis of numerous methamphetamine samples show clear differentiation for ephedrine and pseudoephedrine-produced samples compared to P2P-produced samples. The carbon isotope differences were confirmed from synthetic route precursor studies. PMID:24378294

  19. A new survey of methamphetamine users in treatment: who they are, why they like "meth," and why they need additional services.

    PubMed

    Maxwell, Jane Carlisle

    2014-05-01

    The quality and quantity of illicit methamphetamine has recently increased due to introduction of a new precursor, 1-phenyl-2-propanone (P2P). This paper updates the problems associated with methamphetamine use. Methamphetamine-using clients (N = 222) entering a Texas program participated in computer-assisted interviews in 2010 and 2011 about routes of administration, other drugs used, severity of dependence, mental and physical health, perceived risks and benefits of use, family history, and abuse and neglect experienced as children and adults. Special needs of this population include therapies for trauma, gender-focused counseling, safe housing, and prevention messages to discourage use of the drug. PMID:24093526

  20. Ontogeny of methamphetamine-induced and cocaine-induced one-trial behavioral sensitization in preweanling and adolescent rats.

    PubMed

    Kozanian, Olga O; Gutierrez, Arnold; Mohd-Yusof, Alena; McDougall, Sanders A

    2012-08-01

    The ontogenetic profile of psychostimulant-induced one-trial behavioral sensitization has not been determined. The purpose of this study was to systematically assess the ontogeny of methamphetamine-induced and cocaine-induced behavioral sensitization across the preweanling and adolescent periods. To this end, rats were injected with methamphetamine, cocaine, or saline in either an activity chamber or home cage during the preweanling [postnatal day (PD) 12, PD 16, or PD 20], preadolescent (PD 24), or adolescent (PD 34) periods. One day later, rats were challenged with the same psychostimulant and locomotion was measured in an activity chamber. The results showed that methamphetamine produced one-trial locomotor sensitization on PD 13 and PD 17; whereas, cocaine-induced behavioral sensitization was only evident on PD 21. The sensitized responding of preweanling rats was not influenced by environmental context. Interestingly, preadolescent and adolescent rats did not exhibit locomotor sensitization. The latter result is generally consistent with past studies showing that rats from the middle and late adolescent periods do not exhibit cocaine-induced one-trial behavioral sensitization. The present results show that methamphetamine, as well as cocaine, can produce one-trial context-independent behavioral sensitization during early ontogeny, but sensitized responding is only apparent within a narrow developmental window. PMID:22732208

  1. Meta-analysis of the association between methamphetamine use and high-risk sexual behavior among heterosexuals.

    PubMed

    Hittner, James B

    2016-03-01

    A large body of research has found that nonheterosexual methamphetamine users engage in substantially higher levels of risky sex compared to nonusers. Considerably fewer studies have examined methamphetamine use and high-risk sex among heterosexuals. The present study is a meta-analysis of the empirical literature on methamphetamine use and high-risk sexual behavior among heterosexual individuals. Four risky sex outcomes were examined: unprotected vaginal intercourse, unprotected anal sex, inconsistent condom use, and sex with multiple partners. Analysis of 24 studies (26 independent samples) including 286,781 individuals found that the pooled mean weighted odds ratios ranged from 1.37 (unprotected vaginal intercourse) to 1.72 (inconsistent condom use), indicating that the odds of engaging in risky sex for heterosexual methamphetamine users is, on average, between 37% and 72% greater than for nonmethamphetamine users. Date of publication, percentage of White Caucasian respondents, and sample size were significant moderators of effect size magnitude. Moreover, symmetry plots revealed little direct evidence for publication bias. It is recommended that future research explore additional categorical and continuous variables as potential moderators of effect size strength. (PsycINFO Database Record PMID:26866782

  2. Community Reactions to Campaigns Addressing Crystal Methamphetamine Use among Gay and Bisexual Men in New York City

    ERIC Educational Resources Information Center

    Nanin, Jose E.; Parsons, Jeffrey T.; Bimbi, David S.; Grov, Christian; Brown, Justin T.

    2006-01-01

    Crystal methamphetamine (aka "crystal meth") use with high-risk sex has become an emerging health problem for gay and bisexual men in New York City since the late 1990s. Public health campaigns were eventually developed to encourage gay and bisexual men to avoid or reconsider using crystal meth. Reactions to three campaigns were measured with a…

  3. Methamphetamine Abuse and Impairment of Social Functioning: A Review of the Underlying Neurophysiological Causes and Behavioral Implications

    ERIC Educational Resources Information Center

    Homer, Bruce D.; Solomon, Todd M.; Moeller, Robert W.; Mascia, Amy; DeRaleau, Lauren; Halkitis, Perry N.

    2008-01-01

    The highly addictive drug methamphetamine has been associated with impairments in social cognitions as evidenced by changes in users' behaviors. Physiological changes in brain structure and functioning, particularly in the frontal lobe, have also been identified. The authors propose a biopsychosocial approach to understanding the effects of…

  4. Behavioral and Social Correlates of Methamphetamine Use in a Population-based Sample of Early and Later Adolescents

    PubMed Central

    Embry, Dennis; Hankins, Martin; Biglan, Anthony; Boles, Shawn

    2009-01-01

    This paper reports relationships between methamphetamine use and behaviors and social influences using data from a population-based survey of 8th- and 11th-grade students in Oregon for the 2001–2003 school years. We analyze methamphetamine use within a general problem behavior framework to identify malleable correlates of behavior for future prevention interventions. We specifically test two models of methamphetamine use employing logistic regression analysis: one comprised of behaviors and traits of the individual students and another focusing on peer and parental influences. This study finds adolescent methamphetamine use related to several problem behaviors. However, the specific problems vary by grade and are moderated by gender. Findings indicate the need for tailored interventions targeting gender/grade-specific behaviors or problems such as antisocial activities, risky sex, and depression, as well as social influences such as peers engaging in antisocial behaviors or using drugs and parents favoring drug use or poorly monitoring or setting limits for their children. PMID:19138821

  5. Effect of Abstinence on Depression, Anxiety, and Quality of Life in Chronic Methamphetamine Users in a Therapeutic Community

    PubMed Central

    Bagheri, Maryam; Mokri, Azarakhsh; Khosravi, Aliakbar; Kabir, Kourosh

    2015-01-01

    Background: During withdrawal, patients experience different symptoms. These symptoms are associated with relapse. Understanding different outcomes of methamphetamine abstinence is useful for finding better treatments for dependence. Objectives: This study aimed to show the effects of abstinence on depression, anxiety, and quality of life in methamphetamine users. Patients and Methods: A prospective quasi-experimental (before and after study) method was used to show the effect of 3 weeks abstinence on depression, anxiety, and quality of life. A convenient sample of addicted people entered into the study and 34 people completed the study. Beck Depression Scale, Cattell Anxiety Inventory and Short Form Health Survey (SF-36) (for assessing quality of life), were used for outcome assessments. Results: The mean depression score after abstinence decreased significantly (P < 0.001). Both hidden and obvious anxiety and total anxiety had a high level at admission and after 3 weeks of abstinence, the mean level of anxiety did not change significantly (P < 0.096). However, the quality of life increased after 3 weeks of abstinence (P < 0.001). Conclusions: Depression and anxiety are prevalent in methamphetamine users. Short-term abstinence improves depression and quality of life but does not improve anxiety in methamphetamine abusers. During follow up of these patients, addressing depression and anxiety is important to achieve better results. PMID:26495258

  6. Manufacturing by-products from, and stereochemical outcomes of the biotransformation of benzaldehyde used in the synthesis of methamphetamine.

    PubMed

    Cox, Matthew; Klass, Gunter; Koo, Christina Wei Min

    2009-08-10

    Clandestine synthesis of methamphetamine in Australia has predominantly started from pseudoephedrine extracted from over the counter cold and flu medications. However, recently introduced restrictions on the sale of these products have made pseudoephedrine much more difficult to obtain. As a result clandestine chemists have had to resort to other means of obtaining the necessary chemical precursors. A recent drug raid (Adelaide, January 2008) resulted in the seizure of an unusual reaction mixture that indicated a novel approach involving the fermentation of glucose by yeast in the presence of benzaldehyde to give 1-hydroxy-1-phenylpropanone, also known as l-phenylacetylcarbinol (l-PAC), a known precursor to ephedrine and pseudoephedrine and hence methamphetamine. A study was undertaken into this process with the aim of determining the characteristic reaction by-products associated with methamphetamine made in this way. The study also looked at the stereochemical selectivity of the fermentation reaction and the stereochemistry of the subsequent reaction products, ephedrine and pseudoephedrine, and the final methamphetamine. PMID:19443151

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

    PubMed Central

    2010-01-01

    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. PMID:20964830

  8. Unanticipated Effect of a Randomized Peer Network Intervention on Depressive Symptoms among Young Methamphetamine Users in Thailand

    ERIC Educational Resources Information Center

    German, D.; Sutcliffe, C. G.; Sirirojn, B.; Sherman, S. G.; Latkin, C. A.; Aramrattana, A.; Celentano, D. D.

    2012-01-01

    We examined the effect on depressive symptoms of a peer network-oriented intervention effective in reducing sexual risk behavior and methamphetamine (MA) use. Current Thai MA users aged 18-25 years and their drug and/or sex network members enrolled in a randomized controlled trial with 4 follow-ups over 12 months. A total of 415 index participants…

  9. A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period.

    PubMed

    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tatsuta, Tomohiro; Morita, Yoshio; Takemura, Motohiko

    2012-01-01

    Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decreases, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naïve male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments. PMID:22079320

  10. Changes in leptin, ghrelin, growth hormone and neuropeptide-Y after an acute model of MDMA and methamphetamine exposure in rats.

    PubMed

    Kobeissy, Firas H; Jeung, Jennifer A; Warren, Matthew W; Geier, Jacqueline E; Gold, Mark S

    2008-03-01

    Club drug abuse is a growing problem in the United States. Beyond addiction and toxicity are endocrine effects which are not well characterized. Specifically, the changes in appetite following exposure to drugs of abuse are an interesting but poorly understood phenomenon. Serum hormones such as leptin, ghrelin, growth hormone (GH), and neuropeptide-Y (NP-Y) are known to affect appetite, but have not been studied extensively with drugs of abuse. In this work, we examine the effects of club drugs 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) and methamphetamine (METH) (doses of 5, 20 and 40 mg/kg) on serum concentrations of these hormones in adult male Sprague-Dawley rats 6, 12, 24 and 48 hours after drug administration. In a dose-dependent manner, MDMA was shown to cause transient significant decreases in serum leptin and GH followed by a base line recovery after 24 hours. Conversely, serum ghrelin increased and normalized after 24 hours. Interestingly, serum NP-Y showed a steady decrease in both treatment of MDMA and METH at different time points and dosages. In humans, abuse of these drugs reduces eating. As evident from these data, acute administration of METH and MDMA had significant effects on different serum hormone levels involved in appetite regulation. Future studies should be performed to see how chronic, low dose drug administration would affect hormone levels and try to answer questions about the physiological mechanisms involved in the anorexic paradigm observed in drug use. PMID:17910739

  11. Reduced Prefrontal Cortex Hemodynamic Response in Adults with Methamphetamine Induced Psychosis: Relevance for Impulsivity.

    PubMed

    Yamamuro, Kazuhiko; Kimoto, Sohei; Iida, Junzo; Kishimoto, Naoko; Nakanishi, Yoko; Tanaka, Shohei; Ota, Toyosaku; Makinodan, Manabu; Kishimoto, Toshifumi

    2016-01-01

    Patients with methamphetamine abuse/dependence often exhibit high levels of impulsivity, which may be associated with the structural abnormalities and functional hypoactivities observed in the frontal cortex of these subjects. Although near-infrared spectroscopy (NIRS) is a simple and non-invasive method for characterizing the clinical features of various psychiatric illnesses, few studies have used NIRS to directly investigate the association between prefrontal cortical activity and inhibitory control in patients with methamphetamine-induced psychosis (MAP). Using a 24-channel NIRS system, we compared hemodynamic responses during the Stroop color-word task in 14 patients with MAP and 21 healthy controls matched for age, sex and premorbid IQ. In addition, we used the Barrett Impulsivity Scale-11 (BIS-11) to assess impulsivity between subject groups. The MAP group exhibited significantly less activation in the anterior and frontopolar prefrontal cortex accompanied by lower Stroop color-word task performance, compared with controls. Moreover, BIS-11 scores were significantly higher in the MAP group, and were negatively correlated with the hemodynamic responses in prefrontal cortex. Our data suggest that reduced hemodynamic responses in the prefrontal cortex might reflect higher levels of impulsivity in patients with MAP, providing new insights into disrupted inhibitory control observed in MAP. PMID:27050450

  12. Predictors of methamphetamine psychosis: history of ADHD-relevant childhood behaviors and drug exposure.

    PubMed

    Salo, Ruth; Fassbender, Catherine; Iosif, Ana-Maria; Ursu, Stefan; Leamon, Martin H; Carter, Cameron

    2013-12-15

    The goal of this study was to extend our previous research that reported a significant association between Attention Deficit Hyperactivity Disorder (ADHD)-relevant childhood behaviors and the frequency of methamphetamine (MA)-induced psychotic symptoms in an expanded sample. 190 participants who met DSM-IV criteria for MA dependence were administered the Methamphetamine Experience Questionnaire that assessed MA-induced psychosis. Data related to MA exposure, comorbid drug use, education, familial psychiatric history and assessments of ADHD-relevant childhood behaviors as measured by the Wender Utah Rating Scale (WURS) were collected. Although WURS scores did not differ between 145 MAP+ and 45 MAP- subjects, MAP+ subjects with higher WURS scores were significantly more likely to report more frequent psychosis. Although mean daily MA dosage did not differ between the MAP+ and MAP- subjects, MAP+ subjects who consumed larger doses of MA were significantly more likely to experience frequent psychosis. These data suggest that ADHD-relevant childhood behaviors may interact with MA exposure to reflect a neurobiological vulnerability related to the emergence of frequent MA-induced psychotic symptoms. These results may elucidate factors that contribute to the psychiatric sequelae of MA abuse. PMID:23896355