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Sample records for 42-year-old male methamphetamine

  1. 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

  2. Disinhibited Exposing Behavior, Hypersexuality, and Erectile Dysfunction as a Consequence of Posttraumatic Stress in a 42-Year-Old Male Patient.

    PubMed

    Petri-Kelvasa, Mirja; Schulte-Herbrüggen, Olaf

    2017-10-01

    Research into sexual dysfunction and its explanations within a cognitive behavioral framework in patients with posttraumatic stress is sparse. In this report, we present the case of a 42-year-old male with severe posttraumatic stress symptoms who displayed apparent exhibitionistic behavior, hypersexual behavior in the form of excessive masturbation, and erectile dysfunction. Differential diagnostics showed that the presented exhibitionistic behavior could be more accurately classified as non-paraphilic disinhibited exposing behavior. Functional behavioral analysis of his sexual behavior suggested that disinhibited exposing and hypersexual behavior served as dysfunctional coping strategies for trauma-associated negative emotions. Erectile dysfunction seemed to be the result of trauma-associated hyperarousal and excessive masturbation. Within the context of operant learning processes, we propose that his sexual behaviors became highly automated and were used as the main strategies to regulate trauma-associated negative emotions. Implications for the diagnoses and suggestions for the conceptualization and incorporation into a cognitive behavioral therapy treatment of posttraumatic stress disorder are made.

  3. Hereditary gingival fibromatosis and sensorineural hearing loss in a 42-year-old man with Jones syndrome.

    PubMed

    Kasaboğlu, O; Tümer, C; Balci, S

    2004-01-01

    Hereditary gingival fibromatosis and sensorineural hearing loss in a 42-year-old man with Jones syndrome: Gingival fibromatosis is a rare disease, which can be seen as an isolated condition or associated with some uncommon syndromes. This case report describes the evaluation and treatment of a 42-year-old male patient with hereditary gingival fibromatosis, sensorineural hearing loss, undescended testis and maxillary odontogenic cyst (Jones Syndrome). Six years follow up of the index patient after the surgery revealed no recurrence of the gingival fibromatosis. This report also describes the anamnestic data of the patient's family that showed progressive deafness and gingival enlargement in three generations.

  4. 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

  5. Chronic pruritic dermatitis and peripheral eosinophilia in a 42-year-old man.

    PubMed

    Belser, Kate; Reddy, Vinitha; Marks, James; Ishmael, Faoud; Kelbel, Theodore

    2016-01-01

    Chronic pruritic dermatitis with or without accompanying peripheral eosinophilia can be caused by a vast array of underlying disorders broadly classified as allergic/immunologic, infectious, or neoplastic. An organized and thorough work up is crucial in order to arrive at a definitive diagnosis enabling appropriate treatment. We present the case of a 42-year-old man with a history of chronic pruritic dermatitis and peripheral eosinophilia in a patient-oriented, problem-solving format including the clinical presentation, physical findings, results of pertinent lab/radiologic studies, differential diagnosis, and final diagnosis with discussion.

  6. Methamphetamine

    MedlinePlus

    ... confidencial 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 ...

  7. A Rare Case of Hamartoma Chest Wall Following Trauma in a 42-year-old Man

    PubMed Central

    Ahmadinejad, Mojtaba; Pour, Asghar Alie; Hosseini, Peyman Khadem; Hashemian, Amir Masoud; Ahmadi, Koorosh

    2016-01-01

    Background: Chest wall mesenchymal hamartoma (CWH) is a distinct and extremely rare tumor-like lesion of the thorax. It usually presents in the neonatal period or in infancy. The common presentation is in the form of a visible chest wall mass with or without respiratory distress. Case presentation: A 42-year-old man with a history of chest wall trauma since 5 years ago was admitted with a swelling of the anterior of the chest wall and during this period has grown slowly. Physical examination showed a left anterior chest wall deformity. Chest radiographs and chest CT showed a left anterolateral chest wall mass involving the fourth and fifth ribs. Thoracotomy was performed. The tumor and involved ribs were resected with a 5cm safe margin. The histopathologic examination showed hamartoma. The patient has been fallowed up since 60 month ago, and has not had any complaints in this time. Result: Despite the rarity of chest wall hematoma, this side effect must always be taken into consideration while studying the chest wall injuries especially in the case of trauma history due to other differential diagnosis and her side effects such as respiratory problems. Conclusion: Although rare, this condition ought to be kept in mind while dealing with hamartoma Chest wall following trauma in order to avoid its complications such as respiratory problems. Surgical excision is usually curative in combination with conservative therapy if possible. PMID:27994306

  8. 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 ...

  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. Copyright © 2016 the American Physiological Society.

  10. The effects of methamphetamine exposure during preadolescence on male and female rats in the water maze.

    PubMed

    McFadden, Lisa M; Matuszewich, Leslie

    2007-12-28

    Exposure to methamphetamine early in life can have lasting effects on cognitive processes. The maturation of neurotransmitter systems targeted by methamphetamine differs by gender during childhood and preadolescence, which could lead to differential long-term effects of early drug exposure. Therefore, the current study assessed whether preadolescent exposure to methamphetamine has gender specific long-term effects on adult spatial memory in rodents. Male and female rats were given 1 daily injection of 0 or 2mg/kg methamphetamine or not handled from PD21-35 and then tested as adults (PD95) in the Morris water maze. In general, male rats performed better than female rats in the water maze task regardless of treatment group. Female rats exposed to methamphetamine from PD21-35 had shorter latencies and took more direct paths to the hidden platform compared to control females during the 4 days of acquisition training and when the hidden platform was moved each day on matching to place trials. Male rats exposed to methamphetamine swam a shorter distance to the hidden platform on the first day of acquisition training, similar to the methamphetamine exposed females. However, the methamphetamine exposed males performed more poorly compared to control males in the matching to place trials. Overall, the current study found that methamphetamine exposure during preadolescence has long-term effects on spatial memory in a gender specific manner. These findings may contribute to our general understanding of the long-term effects of psychostimulant exposure at early developmental stages.

  11. Methamphetamine

    MedlinePlus

    ... Store methamphetamine in a safe place so that no one else can take it accidentally or on purpose. ... unable to lose weight. Methamphetamine is in a class of medications called central nervous system stimulants. It works by changing the amounts of certain natural substances in the brain.

  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. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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 ...

  14. Juvenile but not adult methamphetamine exposure improves performance in the Morris Water Maze in male rats.

    PubMed

    Moenk, Michael D; Matuszewich, Leslie

    2012-06-01

    Early exposure to psychostimulants has been found to lead to long-lasting effects on cognitive processes. Our lab has previously reported that juvenile male rats administered methamphetamine showed improved performance in a spatial navigation task when tested in adulthood (McFadden and Matuszewich, 2007). What is not known, however, is if these effects are specific to the developing rat, or if a similar methamphetamine protocol given to adult rats would lead to an equally beneficial long-term change in spatial cognition. In the current study, male rats were given 1 daily injection of 2mg/kg methamphetamine or saline for 15 days during either preadolescence (PD20-34) or adulthood (PD70-84). Approximately 45 days after treatment, all rats then underwent 5 days of place training in the Morris water maze at a time when juvenile rats reached adulthood. Similar to previous findings, juvenile rats exposed to repeated methamphetamine displayed shorter latencies and distances to reach the platform throughout training compared to saline-treated rats. The juvenile rats treated with methamphetamine also swam shorter distances and had faster latencies to the hidden platform compared to adult methamphetamine-treated rats. There were no significant differences in rats treated in adulthood with methamphetamine compared to saline-treated rats. Likewise, there were no effects of prior methamphetamine treatment or age on matching-to-place trials or visible platform trials. Overall, the results show that repeated methamphetamine exposure can selectively improve spatial learning in adult male rats when administered during preadolescence, but does not significantly affect spatial learning when administered in adulthood. Furthermore, the current findings demonstrate the unique susceptibility of the developing brain to drugs that modulate dopaminergic activity, as well as the long-term behavioral impact of exposure at critical ages.

  15. Methamphetamine induces abnormal sperm morphology, low sperm concentration and apoptosis in the testis of male rats.

    PubMed

    Nudmamud-Thanoi, S; Thanoi, S

    2011-08-01

    Methamphetamine has been reported to be an important drug in the field of reproductive toxicology. The aim of this study was to investigate the effects of methamphetamine administrations on sperm morphology, sperm concentration and apoptotic activity inside seminiferous tubule in male rats. Rats were administered a dose of 8 mg kg(-1) , intraperitoneally (IP), for acute group and a dose of 4 mg kg(-1) , IP, once daily for 14 days for sub-acute group. Percentage of normal sperm morphology was decreased in acute group when compared with control. Total numbers of sperm count were significantly decreased in acute and sub-acute groups. Apoptotic activities were most abundant in the seminiferous tubules of acute treated animals with a highly significant increase in the number of apoptotic cells per tubule. Those effects of methamphetamine seem to be dose-dependent. The results suggest that methamphetamine not only works as drug of abuse in central nervous system, but also in gametogenesis of males.

  16. Chronic preexposure to methylphenidate cross-sensitizes methamphetamine in male Japanese quail.

    PubMed

    Rosine, Bobbi Jo; Levi Bolin, B; Akins, Chana K

    2009-07-01

    An increasing debate exists about the potential of exposure to methylphenidate increasing later risk of drug abuse. The objective of this study was to investigate whether chronic preexposure to methylphenidate would induce cross-sensitization to a subsequent methamphetamine challenge in male Japanese quail. Male quail were treated intraperitoneally with either 5, 10, or 20 mg/kg methylphenidate or saline for 14 days. After a 14-day washout period, birds were challenged with 5.6 mg/kg of methamphetamine. Methylphenidate-induced behavioral sensitization was not evident after 14 days of preexposure. However, locomotor activity was greater during the methamphetamine challenge in birds that were preexposed to a high dose of methylphenidate. The findings suggest that chronic preexposure to methylphenidate may be sufficient to alter later responding to methamphetamine, regardless of whether preexposure resulted in behavioral sensitization.

  17. Bupropion Attenuates Methamphetamine Self-Administration in Adult Male Rats

    PubMed Central

    Reichel, Carmela M.; Murray, Jennifer E.; Grant, Kathleen M.; Bevins, Rick A.

    2010-01-01

    Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg IP) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025 to 0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific. PMID:19010609

  18. Bupropion attenuates methamphetamine self-administration in adult male rats.

    PubMed

    Reichel, Carmela M; Murray, Jennifer E; Grant, Kathleen M; Bevins, Rick A

    2009-02-01

    Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg i.p.) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025-0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific.

  19. Methamphetamine impairs sexual motivation but not sexual performance in male Japanese quail.

    PubMed

    Bolin, B Levi; Akins, Chana K

    2009-02-01

    The present study investigated the effects of chronic pre-exposure to methamphetamine on sexual motivation and performance in male Japanese quail. Quail were pre-exposed to methamphetamine (1.0 or 3.0 mg/kg ip) or saline (ip) once daily for 10 days and locomotor activity was measured. After a 10 day washout period, sexual motivation was measured in a straight-arm runway with visual access to a female at one end. Three to 5 hr after sexual motivation tests, males were allowed to copulate with a receptive female quail and copulatory behavior was assessed. Tests were conducted once per day for 10 days. Results showed that males pre-exposed to methamphetamine had decreased locomotor activity compared to saline controls. Males pre-exposed to METH later ran slower toward a female in the runway and spent less time near her. In contrast, methamphetamine pre-exposed males showed similar copulatory behavior as saline pre-exposed males. The findings suggest that chronic pre-exposure to methamphetamine may impair sexual motivation but not sexual performance. The findings are discussed from a comparative perspective and with regard to their clinical relevance.

  20. Training response to high-intensity interval training in a 42-year-old man with chronic spinal cord injury.

    PubMed

    Harnish, Christopher R; Daniels, Jonathan A; Caruso, Deborah

    2017-03-01

    To review the outcome of 12 weeks of periodized, high-intensity interval training (HIT) in a man with chronic traumatic spinal cord injury (SCI). A 42-year-old man (180 cm tall, 68.4 kg and 32.0% Fat) with a C8/T1 motor complete SCI took part in 12 weeks of 3 days per week arm crank ergometry (ACE) interval training. Training consisted of a combination of HIT that included three times 5  min at ∼70% Peak Power (WPeak) and 5  min recovery (HIT5); four times 2.5  min at ∼85% WPeak and 5  min recovery (HIT2.5); ten times 1  min at ∼110% WPeak and 2  min recovery (HIT1). Heart rate (HR) zones were set as <75% HRPeak (Z1), 75-89% (Z2), and 90+% (Z3) and used to monitor overall training efficacy. Thirty-six sessions that included 8 HIT5, 10 HIT2.5, and 5 HIT1 sessions were completed. WPeak and VO2 Peak improved about 45% and 52%, respectively, by week 6, without further improvement at week 12, HR TRIMP scores and power in training sessions trended upward over the 12-week program. Twelve weeks of HIT resulted in a large increase in peak aerobic power, as well as submaximal endurance performance in our participant. The early plateau in maximal testing supports the use of submaximal training assessment important in the long-term training monitoring for SCI.

  1. Effects of methamphetamine on alloparental behavior in male and female prairie voles.

    PubMed

    Perry, Adam N; Ortiz, Richard J; Hernandez, Keziah R; Cushing, Bruce S

    2017-09-14

    Psychostimulant abuse is associated with a variety of impairments in social functioning, including an increased frequency of depression and aggression and deficits in social cognition. Psychostimulants reduce social investigation in rats and mice; however, it is less clear how other forms of social behavior (e.g., prosocial behavior) are affected. Females are also generally more sensitive to the effects of psychostimulants on locomotion and stereotyped behavior, which suggests that females might also display greater disruption of prosocial behavior. In order to test the hypothesis that psychostimulants reduce prosocial behavior and that females are more vulnerable, we treated adult male and female prairie voles with methamphetamine for three days (0, 0.2 or 2.0mg/kg, i.p.) and examined effects on locomotion and alloparental behavior. The lower methamphetamine dose increased activity in the open field in males and reduced locomotion in females. Methamphetamine-treated males took longer to enter the pup chamber, but both sexes displayed reduced pup contact following treatment with the lower methamphetamine dose. The methamphetamine-induced reduction in prosocial behavior was not associated with changes in pup-directed aggression in males or females. In order to investigate potential mechanisms underlying these changes in behavior, we measured adrenal weights as a proxy for activation of the hypothalamic-pituitary-adrenal (HPA) axis. The higher methamphetamine dose increased adrenal weights. Collectively, these data demonstrate that methamphetamine administration reduces alloparental behavior in both sexes and that females are more sensitive to some of the effects of this drug (e.g., locomotion/stereotyped behavior and possibly stimulation of the HPA axis). Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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

  3. 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

  4. Pavlovian discriminative stimulus effects of methamphetamine in male Japanese quail (Coturnix japonica).

    PubMed

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

    2014-07-01

    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.

  5. Maternal separation increases methamphetamine-induced damage in the striatum in male, but not female rats.

    PubMed

    Hensleigh, Emily; Pritchard, Laurel M

    2015-12-15

    Methamphetamine abuse impacts the global economy through costs associated with drug enforcement, emergency room visits, and treatment. Previous research has demonstrated early life stress, such as childhood abuse, increases the likelihood of developing a substance abuse disorder. However, the effects of early life stress on neuronal damage induced by binge methamphetamine administration are unknown. We aimed to elucidate the effects of early life stress on methamphetamine induced dopamine damage in the striatum. Pups were separated from dams for 3h per day during the first two weeks of development or 15 min for control. In adulthood, rats received either subcutaneous 0.9% saline or 5.0mg/kg METH injections every 2h for a total of four injections. Rectal temperatures were taken before the first injection and 1h after each subsequent injection. Seven days after treatment, rats were euthanized and striatum was collected for quantification of tyrosine hydroxylase (TH) and dopamine transporters (DAT) content by Western blot. Methamphetamine significantly elevated core body temperature in males and decreased striatal DAT and TH content, and this effect was potentiated by early life stress. Females did not exhibit elevated core body temperatures or changes in DAT or TH in either condition. Results indicate maternal separation increases methamphetamine induced damage, and females are less susceptible to methamphetamine induced damage. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. A Qualitative Study of the Relationship Between Methamphetamine Abuse and Sexual Dysfunction in Male Substance Abusers

    PubMed Central

    Dolatshahi, Behrouz; Farhoudian, Ali; Falahatdoost, Mozhgan; Tavakoli, Mahmoud; Rezaie Dogahe, Ebrahim

    2016-01-01

    Background Increased prevalent use of methamphetamine is a global public challenge. Information on drug use can be helpful in preventing high-risk behavior related to drug abuse. Objectives This study aims to investigate the sexual function changes related to methamphetamine use in the male clients of public and private addiction treatment centers. Patients and Methods In this qualitative study, 45 men (35 methamphetamine users, 5 family members of the users, and 5 psychiatrists or physicians who were famous for treating or researching addiction) are involved. An in-depth interview was done with therapists and key individuals. Results The results show that the effects of methamphetamine on sexual function are not identical. The first usage is concomitant with the increased duration of sex, an increase in the quality and quantity of sexual pleasure, a delighted orgasm, and feeling more control of the sex act. These effects gradually decrease. A decreased libido and various sexual dysfunctions such as erectile dysfunction, premature ejaculation, and losing control during the sex act will appear over time. Conclusions There are differences in the libido and sexual functions of methamphetamine users. Personal perceptions of one’s sexual function may be affected by cognitive changes resultant from the drug. Drug-use prevention, addiction treatments, appropriate sexual behavior education, and harm reduction are priorities. PMID:27803891

  7. Developmental lead exposure alters methamphetamine self-administration in the male rat: acquisition and reinstatement.

    PubMed

    Rocha, Angelica; Valles, Rodrigo; Bratton, Gerald R; Nation, Jack R

    2008-05-01

    The rate of acquisition of drug self-administration and the return to drug seeking are important elements of the overall drug profile, and are essential factors in understanding risks associated with drug abuse. Experiment 1 examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) methamphetamine self-administration. Experiment 2 investigated the effects of perinatal lead exposure on drug-maintained responding in a reinstatement (relapse) paradigm. In Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Lead exposure continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). Male rats born to control or lead-exposed dams were tested daily as adults in an acquisition paradigm that incorporated both Pavlovian and operant components. An initial 3-h autoshaping period preceded a 3-h self-administration period. For 35 daily training sessions i.v. methamphetamine infusions [inf] (0.02 mg/kg) were paired with the extension and retraction of a lever (autoshaping), while inf occurred during self-administration only when a lever press was executed (FR-1). In Experiment 2 animals developmentally exposed to lead were trained on an FR-2 to self-administer methamphetamine (0.04 mg/kg/inf) and then placed on an extinction schedule prior to receiving intraperitoneal (i.p.) priming injections of saline, 0.50, 1.00, or 1.50 mg/kg methamphetamine. The findings from Experiment 1 showed that acquisition was delayed in rats born to lead-exposed dams gavaged daily with 16 mg lead throughout gestation and lactation when a 0.02-mg/kg/inf of methamphetamine served as the reinforcement outcome. Additional data from Experiment 2 indicated priming cues (injections of methamphetamine [i.p.]) administered after extinction were less likely to occasion a return to drug seeking (relapse) in the 16-mg group relative to the 0-mg

  8. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. 96-hour methamphetamine self-administration in male and female rats: a novel model of human methamphetamine addiction.

    PubMed

    Cornett, Elyse M; Goeders, Nicholas E

    2013-10-01

    Methamphetamine (MA) is a highly addictive psychostimulant drug of abuse for which no FDA-approved treatment exists. While high on MA, both male and female MA users report engaging in risky behaviors and are more likely to be involved in violent criminal activities and to engage in domestic and sexual violence. A unique aspect of MA is that it is typically used in binges. However, there is no animal model of MA self-administration that appears to represent a human MA self-administration binge. We recently developed a 96-hour MA self-administration paradigm in rats that more closely resembles how human MA users take the drug. Male and female rats were trained to self-administer MA for 96 consecutive hours for 5 weeks. Responding by female and male rats tended to escalate to binge-like behavior, as the animals responded continuously during their normal periods of activity as well as during their inactive periods for up to 72 h, followed by a crash of 6 or more hours. Thus, this 96-hour model of MA self-administration is a novel way to study MA addition in rats that may contribute to the development of improved treatments for recovering human MA users.

  10. Getting Off: development of a model program for gay and bisexual male methamphetamine users.

    PubMed

    Reback, Cathy J; Veniegas, Rosemary; Shoptaw, Steven

    2014-01-01

    An evidence-based gay-specific cognitive behavioral therapy (GCBT) intervention for methamphetamine-using gay and bisexual men was adapted for use in a community-based setting, thereby moving research into practice. The 48-session, 16-week GCBT intervention was revised to 24 sessions requiring 8 weeks and renamed Getting Off: A Behavioral Treatment Intervention for Gay and Bisexual Male Methamphetamine Users. GCBT was modified for implementation within the limited resources and capacity of community-based organizations while also retaining drug use and HIV risk reduction outcomes. Since 2007, Getting Off has been sustained with public health funding at the community site and has been adopted by multiple community-based sites.

  11. Interactions between Early Life Stress, Nucleus Accumbens MeCP2 Expression, and Methamphetamine Self-Administration in Male Rats.

    PubMed

    Lewis, Candace R; Bastle, Ryan M; Manning, Tawny B; Himes, Sarah M; Fennig, Paulette; Conrad, Phoebe R; Colwell, Jenna; Pagni, Broc A; Hess, Lyndsay A; Matekel, Caitlin G; Newbern, Jason M; Olive, M Foster

    2016-11-01

    Early life stress (ELS) is highly related to the development of psychiatric illnesses in adulthood, including substance use disorders. A recent body of literature suggests that long-lasting changes in the epigenome may be a mechanism by which experiences early in life can alter neurobiological and behavioral phenotypes in adulthood. In this study, we replicate our previous findings that ELS, in the form of prolonged maternal separation, increases adult methamphetamine self-administration (SA) in male rats as compared with handled controls. In addition, we show new evidence that both ELS and methamphetamine SA alter the expression of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2) in key brain reward regions, particularly in the nucleus accumbens (NAc) core. In turn, viral-mediated knockdown of MeCP2 expression in the NAc core reduces methamphetamine SA, as well as saccharin intake. Furthermore, NAc core MeCP2 knockdown reduces methamphetamine, but not saccharin, SA on a progressive ratio schedule of reinforcement. These data suggest that NAc core MeCP2 may be recruited by both ELS and methamphetamine SA and promote the development of certain aspects of drug abuse-related behavior. Taken together, functional interactions between ELS, methamphetamine SA, and the expression of MeCP2 in the NAc may represent novel mechanisms that can ultimately be targeted for intervention in individuals with adverse early life experiences who are at risk for developing substance use disorders.

  12. Methamphetamine acts on subpopulations of neurons regulating sexual behavior in male rats

    PubMed Central

    Frohmader, Karla S.; Wiskerke, Joost; Wise, Roy A.; Lehman, Michael N.; Coolen, Lique M.

    2010-01-01

    Methamphetamine (Meth) is a highly addictive stimulant. Meth abuse is commonly associated with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus and Meth users report heightened sexual desire, arousal, and sexual pleasure. The biological basis for this drug-sex nexus is unknown. The current study demonstrates that Meth administration in male rats activates neurons in brain regions of the mesolimbic system that are involved in the regulation of sexual behavior. Specifically, Meth and mating co-activate cells in the nucleus accumbens core and shell, basolateral amygdala, and anterior cingulate cortex. These findings illustrate that in contrast to current belief drugs of abuse can activate the same cells as a natural reinforcer, i.e. sexual behavior, and in turn may influence compulsive seeking of this natural reward. PMID:20045448

  13. The Pharmacokinetics of Methamphetamine Self-Administration in Male and Female Rats

    PubMed Central

    Milesi-Hallé, Alessandra; Hambuchen, Michael D.; McMillan, Donald E.; Owens, S. Michael

    2015-01-01

    Background Because methamphetamine (METH) pharmacokinetics after single iv doses show significant differences between male and female rats, we hypothesized that pharmacokinetic differences in METH disposition could be a contributing factor to the patterns of METH self-administration behaviors in rats. Methods For the studies, we used a passive (non-contingent) METH dosing schedule consisting of 27 METH iv bolus injections (0.048 mg/kg) over 2 hrs derived from a previous active (contingent) METH self-administration behavioral study in male rats. After METH dosing of male and female Sprague-Dawley rats (n=5/group), METH and amphetamine serum concentrations were determined by LC-MS/MS. Pharmacokinetic analysis, including predictive mathematical simulations of the data, was then conducted. Results Male and female rats achieved relatively stable METH serum concentrations within 20 min, which remained constant from 20–120 min. While not statistically different, METH clearance and volume of distribution values for females were 25% and 33% lower (respectively) than males. Linear regression analysis of predicted METH concentrations from pharmacokinetic simulations versus observed concentrations showed a substantially better correlation with male data than female data (r2 = 0.71 vs. 0.56; slope = 0.95 vs. 0.45, respectively). At 120 min, the time of predicted peak METH serum concentrations, female values were 42% higher than expected, while male values were within 3%. Conclusions Unlike METH male pharmacokinetic data, the female data was less predictable during multiple METH administrations and produced overall higher than expected METH concentrations. These findings demonstrate that METH pharmacokinetics could contribute to differences in METH self-administration behaviors in rats. PMID:25796510

  14. The pharmacokinetics of methamphetamine self-administration in male and female rats.

    PubMed

    Milesi-Hallé, Alessandra; Hambuchen, Michael D; McMillan, Donald E; Michael Owens, S

    2015-05-01

    Because methamphetamine (METH) pharmacokinetics after single iv doses show significant differences between male and female rats, we hypothesized that pharmacokinetic differences in METH disposition could be a contributing factor to the patterns of METH self-administration behaviors in rats. For the studies, we used a passive (non-contingent) METH dosing schedule consisting of 27 METH iv bolus injections (0.048mg/kg) over 2h derived from a previous active (contingent) METH self-administration behavioral study in male rats. After METH dosing of male and female Sprague-Dawley rats (n=5/group), METH and amphetamine serum concentrations were determined by LC-MS/MS. Pharmacokinetic analysis, including predictive mathematical simulations of the data, was then conducted. Male and female rats achieved relatively stable METH serum concentrations within 20min, which remained constant from 20 to 120min. While not statistically different, METH clearance and volume of distribution values for females were 25% and 33% lower (respectively) than males. Linear regression analysis of predicted METH concentrations from pharmacokinetic simulations versus observed concentrations showed a substantially better correlation with male data than female data (r(2)=0.71 vs. 0.56; slope=0.95 vs. 0.45, respectively). At 120min, the time of predicted peak METH serum concentrations, female values were 42% higher than expected, while male values were within 3%. Unlike METH male pharmacokinetic data, the female data was less predictable during multiple METH administrations and produced overall higher than expected METH concentrations. These findings demonstrate that METH pharmacokinetics could contribute to differences in METH self-administration behaviors in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

    Schwienteck, Kathryn L.; Banks, Matthew L.

    2015-01-01

    Background Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice.In addition, 7-day cocaine treatment effects were also examined. Methods Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1 mg/kg/h), methylphenidate (0.032-0.32 mg/kg/h), or cocaine (0.1-0.32 mg/kg/h). Results During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1 mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. Conclusions The present subchronic treatment resultssupport the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. PMID:26361713

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

    PubMed

    Schwienteck, Kathryn L; Banks, Matthew L

    2015-10-01

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

  18. Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone.

    PubMed

    Holtz, Nathan A; Lozama, Anthony; Prisinzano, Thomas E; Carroll, Marilyn E

    2012-01-01

    Sex differences in methamphetamine (METH) use (females>males) have been demonstrated in clinical and preclinical studies. This experiment investigated the effect of sex on the reinstatement of METH-seeking behavior in rats and determined whether pharmacological interventions for METH-seeking vary by sex. Treatment drugs were modafinil (MOD), an analeptic, and allopregnanolone (ALLO), a neuroactive steroid and progesterone metabolite. Male and female rats were trained to self-administer i.v. infusions of METH (0.05 mg/kg/infusion). Next, rats self-administered METH for a 10-day maintenance period. METH was then replaced with saline, and rats extinguished lever-pressing behavior over 18 days. A multi-component reinstatement procedure followed whereby priming injections of METH (1mg/kg) were administered at the start of each daily session, preceded 30 min by MOD (128 mg/kg, i.p.), ALLO (15 mg/kg, s.c.), or vehicle treatment. MOD was also administered at the onset of the session to determine if it would induce the reinstatement of METH-seeking behavior. Female rats had greater METH-induced reinstatement responding compared to male rats following control treatment injections. MOD (compared to the DMSO control) attenuated METH-seeking behavior in male and female rats; however, ALLO only reduced METH-primed responding in females. MOD alone did not induce the reinstatement of METH-seeking behavior. These results support previous findings that females are more susceptible to stimulant abuse compared to males, and ALLO effectively reduced METH-primed reinstatement in females. Further, results illustrate the utility of MOD as a potential agent for prevention of relapse to METH use in both males and females. Published by Elsevier Ireland Ltd.

  19. Effect of amphetamine on adult male and female rats prenatally exposed to methamphetamine.

    PubMed

    Šlamberová, Romana; Macúchová, Eva; Nohejlová, Kateryna; Štofková, Andrea; Jurčovičová, Jana

    2014-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

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

    PubMed

    Banks, Matthew L

    2016-08-01

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

  1. Exploratory studies in sensory reinforcement in male rats: effects of methamphetamine.

    PubMed

    Gancarz, Amy M; Ashrafioun, Lisham; San George, Michele A; Hausknecht, Kathy A; Hawk, Larry W; Richards, Jerry B

    2012-02-01

    Understanding sensory reinforcement and the effects of stimulant drugs on sensory reinforcers is potentially important for understanding their influence on addiction processes. Experiment 1 explored the reinforcing properties of a visual stimulus and the effects of methamphetamine (METH) on responding maintained by a visual reinforcer (VRF) in male rats. Snout poke responses to the active alternative produced the VRF according to variable interval (VI) schedules of reinforcement, and responses to an inactive alternative had no programmed effect. Experiment 2 explored the effects of METH on choice between the VRF and a water reinforcer (H2ORF) using concurrent VI schedules in male rats. In Experiment 1, response-contingent onset of the VRF produced an increase in both the relative frequency and absolute rate of active responding. The rate of both active and inactive responding declined across the 40-min test sessions. METH did not differentially enhance active responding for the VRF. Instead, METH nondifferentially increased the rate of responding and attenuated the within-session decline of responding. In Experiment 2, METH differentially increased the rate of responding for the VRF relative to the H2ORF. The results of these exploratory experiments indicate that the reinforcing effects of the VRF were weak and transient. In addition, METH treatment increased responding, and the specificity of the enhancement of METH was dependent upon the testing conditions. Potential explanations of these differences, such as novelty and reinforcer type, are discussed.

  2. 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

  3. Methamphetamine (Meth)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Methamphetamine (Meth) KidsHealth > For Teens > Methamphetamine (Meth) A A ... How Can Someone Quit? Avoiding Meth What Is Methamphetamine? Methamphetamine, or meth, is a powerful stimulant drug. ...

  4. Methamphetamine (Meth)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Methamphetamine (Meth) KidsHealth > For Teens > Methamphetamine (Meth) Print A ... Quit? Avoiding Meth en español Metanfetamina What Is Methamphetamine? Methamphetamine, or meth, is a powerful stimulant drug. ...

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

    PubMed

    Asante, Kwaku Oppong; Lentoor, Antonio G

    2017-03-27

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

  6. Chronic pre-exposure to methamphetamine following 31 days of withdrawal impairs sexual performance but not sexual conditioning in male Japanese quail

    PubMed Central

    Bolin, B. Levi; Akins, Chana K.

    2012-01-01

    In the current study, male quail were administered methamphetamine (3.0 or 5.6 mg/kg IP) or saline once-daily for 10 days and locomotor activity was assessed. Following a 31-day withdrawal period, sexual conditioning trials were conducted such that a conditioned stimulus (CS) was presented prior to a copulatory opportunity with a female quail. Male quail treated with methamphetamine (5.6 mg/kg) showed a decrease in locomotor activity from Trial 1 to Trial 10 suggesting a potential tolerance effect. Following the 31-day withdrawal period, all male quail that received the CS paired with a copulatory opportunity showed enhanced approach to the CS, regardless of treatment history. Thus, chronic pre-exposure to methamphetamine did not alter sexual conditioning. In contrast, chronic pre-exposure to methamphetamine (3.0 mg/kg) decreased the frequency of successful copulations suggesting that it impaired sexual performance. The findings suggest that methamphetamine may differentially affect the neural circuitry involved in motivational systems compared with those involved in consummatory aspects of sexual behavior. These effects may last long after drug cessation. PMID:22835652

  7. Chronic pre-exposure to methamphetamine following 31 days of withdrawal impairs sexual performance but not sexual conditioning in male Japanese quail.

    PubMed

    Bolin, B Levi; Akins, Chana K

    2012-10-01

    In the current study, male quail were administered methamphetamine (3.0 or 5.6 mg/kg IP) or saline once daily for 10 days and locomotor activity was assessed. Following a 31-day withdrawal period, sexual conditioning trials were conducted such that a conditioned stimulus (CS) was presented prior to a copulatory opportunity with a female quail. Male quail treated with methamphetamine (5.6 mg/kg) showed a decrease in locomotor activity from Trial 1 to Trial 10 suggesting a potential tolerance effect. Following the 31-day withdrawal period, all male quail that received the CS paired with a copulatory opportunity showed enhanced approach to the CS, regardless of treatment history. Thus, chronic pre-exposure to methamphetamine did not alter sexual conditioning. In contrast, chronic pre-exposure to methamphetamine (3.0 mg/kg) decreased the frequency of successful copulations suggesting that it impaired sexual performance. The findings suggest that methamphetamine may differentially affect the neural circuitry involved in motivational systems compared with those involved in consummatory aspects of sexual behavior. These effects may last long after drug cessation. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio responding in the male rat.

    PubMed

    Rocha, Angelica; Valles, Rodrigo; Hart, Nigel; Bratton, Gerald R; Nation, Jack R

    2008-06-01

    Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.; Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation J.R. Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead. Because the mainstream popularity of methamphetamine in the United States is increasing and lead exposure continues to be widespread, an examination of this drug and how it may be modified by perinatal exposure to lead is warranted. The studies reported here examined the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across the maintenance phase of drug addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed animals. Experiment 2 evaluated control and lead-exposed animals in a progressive ratio task. Female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 70) and subsequently were randomly assigned to one of the two studies, using only one male rat per litter for each study. The data showed a general attenuation of

  9. Methamphetamine abuse: a review of the literature and case report in a young male.

    PubMed

    Naidoo, S; Smit, D

    2011-04-01

    Methamphethamine (TIK) is a highly addictive drug that acts as a stimulant for the central nervous system. It increases wakefulness and physical activity and can cause cardiac dysrhythmias, hypertension, hallucinations and violent behavior. Dental patients abusing methamphetamine often present with poor oral hygiene, xerostomia, rampant caries ("meth mouth") and excessive tooth wear. Management of these conditions is often challenging. A 24-year-old Caucasian man presented with severe dental pain, halitosis and self-reported poor dental appearance. A comprehensive examination including his medical history, panoramic radiographs and extra- and intraoral examination revealed 19 carious and erosive lesions. He reported using methamphetamine for eleven years and had not experienced much caries prior to using the drug. The patient's medical and dental histories along with radiographic and clinical findings led to a diagnosis of "meth mouth." Although various dental treatment options were offered to the patient, he opted for extraction of the most painful teeth in the left lower madibular quadrant and has yet to return for further treatment. This literature review and clinical case description of the oral manifestations of "meth mouth" is intended to alert dental practitioners to recognize and manage patients who are abusing methamphetamines. They should also be aware that these patients are often unreliable at following prevention advice as well as keeping follow-up appointments.

  10. Nicotine exposure beginning in adolescence enhances the acquisition of methamphetamine self-administration, but not methamphetamine-primed reinstatement in male rats.

    PubMed

    Pipkin, Joseph A; Kaplan, Graham J; Plant, Christopher P; Eaton, Shannon E; Gil, Susan M; Zavala, Arturo R; Crawford, Cynthia A

    2014-09-01

    Nicotine is commonly abused in adolescence and is believed to be a "gateway" to other drugs of abuse [e.g., methamphetamine (METH)]. The relationship between early nicotine exposure and later METH use is complicated because the majority of juvenile smokers continue to use cigarettes into adulthood. Thus, the present investigation examined the individual and combined contribution of adolescent and adult nicotine exposure on METH self-administration. Forty-three male rats were pretreated with saline or nicotine (0.16 or 0.64 mg/kg, SC) from postnatal day (PD) 35-50. On PD 51, subjects were split into the following groups: SAL-SAL, 0.16-0.16, 0.16-SAL, 0.64-0.64, and 0.64-SAL. Rats were then trained to lever press for METH (0.05 mg/kg) for seven days on an FR1 and seven days on an FR3 reinforcement schedule. After acquisition training, rats underwent 14 days of extinction and were then tested for METH-induced primed reinstatement (1.0mg/kg, IP). Data showed that rats receiving continuous injections of the low dose of nicotine (0.16-0.16) obtained more METH infusions versus the control group (SAL-SAL) on an FR1 and FR3 schedule. In addition, rats on the FR3 schedule that received a low dose of nicotine during the adolescent period only (0.16-SAL) had more METH intake than the control group (SAL-SAL). Interestingly, the high dose of nicotine exposure had no effect on METH intake and neither nicotine dose altered METH seeking behavior. Low dose exposure to nicotine during adolescence enhances the reinforcing effects of METH, while heavier exposure has no effect on METH intake. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. 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.

  12. Sex Differences in (+)-Amphetamine- and (+)-Methamphetamine-induced Behavioral Response in Male and Female Sprague-Dawley Rats

    PubMed Central

    Milesi-Hallé, Alessandra; McMillan, Donald E.; Laurenzana, Elizabeth M.; Byrnes-Blake, Kelly A.; Owens, S. Michael

    2007-01-01

    (+)-Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, the current studies sought to test the hypothesis that the behavioral and temporal actions of METH and AMP should be greater in female Sprague-Dawley rats than in males. Using a dosing regimen designed to reduce the possibility of tolerance and sensitization, rats were administered 1.0 and 3.0 mg/kg intravenous drug doses. Distance traveled, rearing events and focal stereotypies (e.g., head weaving, sniffing) were measured. Female rats traveled significantly greater distances and displayed a greater number of rearing events than males after both doses. Analysis of stereotypy ratings after 3.0 mg/kg revealed that focal stereotypies were more pronounced and lasted longer in females. The second study compared the potencies of METH and AMP in inducing locomotor activity and focal stereotypies in each sex. No differences in potency were found when METH and AMP effects were compared within males or females. In summary, these studies showed female rats displayed greater and longer-lasting locomotor activity and more stereotypic behaviors, supporting earlier evidence of significant sexual dimorphism in pharmacokinetics. PMID:17275894

  13. Chronic methamphetamine self-administration alters cognitive flexibility in male rats.

    PubMed

    Cox, Brittney M; Cope, Zackary A; Parsegian, Aram; Floresco, Stan B; Aston-Jones, Gary; See, Ronald E

    2016-06-01

    Methamphetamine (meth) addiction is a chronically relapsing disorder that often produces persistent cognitive deficits. These include decreased cognitive flexibility, which may prevent meth addicts from altering their habitual drug abuse and leave them more susceptible to relapse. Multiple factors including low rates of compliance with research study participation and varied drug use patterns make the relationship between cognitive flexibility and relapse difficult to establish in clinical populations. Here, we combined an extended-access meth self-administration paradigm with an automated set-shifting task in rats to directly compare cognitive flexibility performance with meth-seeking behavior. Rats were pre-trained on an automated visual discrimination task, followed by 14 days of extended access (6 h/day) of meth or sucrose self-administration. They were then tested in the set-shifting task on strategy shift and reversal and subsequently assessed for cue-induced reinstatement of meth seeking. Rats with a history of meth, but not sucrose, self-administration had selective deficits in reversal learning. Specifically, meth rats had an increase in the total number of errors and perseverative errors (corresponding to the old stimulus-reward association) following the reversal shift, which correlated with prior stable meth self-administration. However, no relationship was seen between errors during the reversal and cue-induced reinstatement. The lack of association between meth-induced reversal deficits and cue-induced reinstatement to meth seeking indicates that these two domains may constitute independent pathologies of meth addiction.

  14. 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.

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

    PubMed Central

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

    2016-01-01

    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 present aim 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. Potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, ≥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

  16. Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats.

    PubMed

    Siemian, Justin N; Xue, Zhaoxia; Blough, Bruce E; Li, Jun-Xu

    2017-07-01

    Both l- and d-methamphetamine (l- and d-MA) are more potent to release norpepinephrine (NE) than dopamine, and the selectivity is greater for l-MA than d-MA. Little is known of the in vivo pharmacology of l-MA. This study compared the effects of l-MA and d-MA in assays of nociception, behavioral disruption, and impulsivity. Antinociceptive effects of d- and l-MA were examined in two pain assays: the warm water tail withdrawal test for acute nociception and the von Frey test in complete Freund's adjuvant (CFA)-treated rats for chronic inflammatory pain. Food-maintained operant responding and locomotion tests were used to assess generalized behavioral disruption. The 5-choice serial reaction time test (5-CSRTT) was used to assess drug-induced effects on impulse control. A delay discounting procedure was used to determine drug-induced changes in sensitivity to reinforcer delay (impulsive choice). l-MA (3.2-10 mg/kg) produced dose-dependent antinociception in both pain assays, decreased the rate of food-maintained operant responding, and decreased locomotor activity at a higher dose (17.8 mg/kg). In contrast, d-MA (0.32-3.2 mg/kg) did not produce antinociception in either assay, produced biphasic effects on response rate, and increased locomotor activity. In the 5-CSRTT, d-MA but not l-MA produced significant increase in premature responses. In the delay discounting procedure, both drugs did not affect the delay function at doses that did not increase omissions. These data suggest that d- and l-MA have different behavioral profiles. Consideration should be given to these differences in future studies when l-MA is proposed for potential therapies.

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

    PubMed Central

    Acevedo, Summer F.; Raber, Jacob

    2011-01-01

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

  18. Chronic methamphetamine self-administration alters cognitive flexibility in male rats

    PubMed Central

    Cox, Brittney M.; Cope, Zackary A.; Parsegian, Aram; Floresco, Stan B.; Aston-Jones, Gary; See, Ronald E.

    2016-01-01

    Rationale Methamphetamine (meth) addiction is a chronically relapsing disorder that often produces persistent cognitive deficits. These include decreased cognitive flexibility, which may prevent meth addicts from altering their habitual drug abuse and leave them more susceptible to relapse. Multiple factors including low rates of compliance with research study participation and varied drug use patterns make the relationship between cognitive flexibility and relapse difficult to establish in clinical populations. Objectives Here, we combined an extended-access meth self-administration paradigm with an automated set-shifting task in rats to directly compare cognitive flexibility performance with meth-seeking behavior. Methods Rats were pre-trained on an automated visual discrimination task, followed by 14 days of extended access (6 h/day) of meth or sucrose self-administration. They were then tested in the set-shifting task on strategy shift and reversal and subsequently assessed for cue-induced reinstatement of meth seeking. Results Rats with a history of meth, but not sucrose, self-administration had selective deficits in reversal learning. Specifically, meth rats had an increase in the total number of errors and perseverative errors (corresponding to the old stimulus-reward association) following the reversal shift, which correlated with prior stable meth self-administration. However, no relationship was seen between errors during the reversal and cue-induced reinstatement. Conclusion The lack of association between meth-induced reversal deficits and cue-induced reinstatement to meth seeking indicates that these two domains may constitute independent pathologies of meth addiction. PMID:27037939

  19. 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.

  20. Cocaine-like discriminative stimulus effects of amphetamine, cathinone, methamphetamine, and their 3,4-methylenedioxy analogs in male rhesus monkeys.

    PubMed

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

    2017-01-01

    Synthetic cathinones have emerged as the newest class of abused monoamine transporter substrates. Structurally, these compounds are all beta-ketone amphetamine (cathinone) analogs. Whether synthetic cathinone analogs produce differential behavioral effects from their amphetamine analog counterparts has not been systematically examined. Preclinical drug discrimination procedures have been useful for determining the structure activity relationships (SARs) of abused drugs; however, direct comparisons between amphetamine and cathinone analogs are lacking and, in particular, in non-human primate models. The study aim was to determine the potency and time course of (±)-amphetamine, (±)-cathinone, and (±)-methamphetamine and their 3,4-methylenedioxy analogs (±)-MDA, (±)-MDC, and (±)-MDMA, respectively, to produce cocaine-like discriminative stimulus effects. If cathinone analogs have similar behavioral pharmacological properties to their amphetamine counterparts, then we would predict similar potencies and efficacies to produce cocaine-like discriminative stimulus effects. Male rhesus monkeys (n = 4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. Racemic amphetamine, cathinone, and methamphetamine produced dose-dependent and full substitution, ≥90 % cocaine-appropriate responding, in all monkeys. Addition of 3,4-methylenedioxy moiety attenuated both the potency and efficacy of amphetamine (MDA), cathinone (MDC), and methamphetamine (MDMA) to produce full cocaine-like effects. Moreover, the cocaine-like effects of amphetamine and cathinone were attenuated to a greater extent than those of methamphetamine or previously published methcathinone (Smith et al. 2016). The presence of an N-methyl group blunted both the potency and the efficacy shift of the 3,4-methylenedioxy addition for both amphetamine and cathinone analogs.

  1. 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

  2. Effect of cross-fostering on seizures in adult male offspring of methamphetamine-treated rat mothers.

    PubMed

    Slamberová, R; Hrubá, L; Bernásková, K; Matejovská, I; Rokyta, R

    2010-10-01

    Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play a role in the effect of stimulants in the genesis of epileptic seizures. Our previous studies showed that prenatal methamphetamine (MA) exposure induced long-term changes in seizure susceptibility. The aim of the present study was to investigate the effect of cross-fostering on the prenatal and postnatal MA-exposed rats, respectively, on their seizures in adulthood. Bicuculline (GABA(A) receptor antagonist), NMDA (NMDA receptor agonist) and flurothyl (a convulsant gas) were used to induce seizures in adult male offsprings. Female dams were injected with MA (5 mg/kg daily) or physiological saline (S) for approx. 9 week [about 3 week prior to impregnation, for the entire gestation period (22 days) and in preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposure) of adult male rats were tested in each seizure test: C/C; C/S; C/MA; S/C; S/S; S/MA; MA/C; MA/S; MA/MA. The present study demonstrates that the effect of prenatal and/or postnatal MA exposure is seizure model specific. In addition, our data show that there is an effect of cross-fostering on seizures; particularly, the effect of prenatal MA exposure shown in animals fostered by control mothers is no longer apparent in animals fostered postnatally by MA-treated mothers. Such effect of postnatal treatment is not manifested in prenatal controls. In summary, it seems that: (1) prenatal MA exposure alters seizure susceptibility more than postnatal MA exposure; (2) especially in seizures induced by chemicals that affect GABAergic system (bicuculline, flurothyl) notable effect of adoption (cross-fostering) is apparent; (3) in seizure models that are

  3. Methamphetamine abuse.

    PubMed

    Winslow, Bradford T; Voorhees, Kenton I; Pehl, Katherine A

    2007-10-15

    Methamphetamine is a stimulant commonly abused in many parts of the United States. Most methamphetamine users are white men 18 to 25 years of age, but the highest usage rates have been found in native Hawaiians, persons of more than one race, Native Americans, and men who have sex with men. Methamphetamine use produces a rapid, pleasurable rush followed by euphoria, heightened attention, and increased energy. Possible adverse effects include myocardial infarction, stroke, seizures, rhabdomyolysis, cardiomyopathy, psychosis, and death. Chronic methamphetamine use is associated with neurologic and psychiatric symptoms and changes in physical appearance. High-risk sexual activity and transmission of human immunodeficiency virus are also associated with methamphetamine use. Use of methamphetamine in women who are pregnant can cause placental abruption, intrauterine growth retardation, and preterm birth, and there can be adverse consequences in children exposed to the drug. Treatment of methamphetamine intoxication is primarily supportive. Treatment of methamphetamine abuse is behavioral; cognitive behavior therapy, contingency management, and the Matrix Model may be effective. Pharmacologic treatments are under investigation.

  4. Early Life Stress and Chronic Variable Stress in Adulthood Interact to Influence Methamphetamine Self-Administration in Male Rats

    PubMed Central

    Lewis, Candace R.; Staudinger, Kelsey; Tomek, Seven E.; Hernandez, Raymundo; Manning, Tawny; Olive, M. Foster

    2015-01-01

    Early life stress interacts with adult stress to differentially modulate neural systems and vulnerability to various psychiatric illnesses. However, the effects of early life stress and adult stress on addictive behaviors have not been sufficiently investigated. We examined the effects of early life stress in the form of prolonged maternal separation followed in early adulthood by either 10 days of chronic variable stress or no stress on methamphetamine self-administration, extinction, and cue-induced reinstatement. We observed that chronic variable stress in adulthood reduced methamphetamine self-administration in rats with a history of early life stress. These findings add to an emerging body of literature suggesting interactions between and early life and early adulthood stressors on adult behavioral phenotypes. PMID:26176409

  5. Early life stress and chronic variable stress in adulthood interact to influence methamphetamine self-administration in male rats.

    PubMed

    Lewis, Candace R; Staudinger, Kelsey; Tomek, Seven E; Hernandez, Raymundo; Manning, Tawny; Olive, M Foster

    2016-04-01

    Early life stress interacts with adult stress to differentially modulate neural systems and vulnerability to various psychiatric illnesses. However, the effects of early life stress and adult stress on addictive behaviors have not been sufficiently investigated. We examined the effects of early life stress in the form of prolonged maternal separation, followed in early adulthood by either 10 days of chronic variable stress or no stress, on methamphetamine self-administration, extinction, and cue-induced reinstatement. We observed that chronic variable stress in adulthood reduced methamphetamine self-administration in rats with a history of early life stress. These findings add to an emerging body of literature suggesting interactions between early life and early adulthood stressors on adult behavioral phenotypes.

  6. Dexmedetomidine use in the ED for control of methamphetamine-induced agitation.

    PubMed

    Lam, Rex Pui Kin; Yip, Wai Lam; Wan, Chi Keung; Tsui, Matthew Sik Hon

    2017-04-01

    Chemical restraint is often required to control agitation induced by methamphetamine. Dexmedetomidine is an α-2 adrenergic receptor agonist with sedative, analgesic, and sympatholytic properties. Its use in the emergency department (ED) to control methamphetamine-induced agitation has not been reported. To report two cases of methamphetamine-induced agitation successfully sedated with dexmedetomidine in the ED. The first case was a 42-year-old man with unstable emotion and violent behaviours after smoking methamphetamine. His agitation did not respond to a large cumulative dose of benzodiazepines (10mg of diazepam and 332mg of midazolam) administered over 48h and sedation was achieved with dexmedetomidine. The second case was a 38-year-old methamphetamine user with unstable emotion and recurrent episodes of agitation despite repeated doses of benzodiazepines, whose agitation was controlled with dexmedetomidine infusion. In both cases, dexmedetomidine apparently reduced the dose of benzodiazepines needed to achieve adequate sedation. Transient falls in blood pressure and slowing of the heart rate were noted, which resolved either spontaneously or after reducing the infusion rate without requiring drug treatment. Dexmedetomidine can be considered as an adjunct for chemical restraint when standard treatment fails to control the agitation induced by methamphetamine, but patient's hemodynamic state should be monitored closely during administration. Its efficacy and safety in the ED warrant further evaluation with prospective controlled trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The effect of neurotoxic doses of methamphetamine on methamphetamine-conditioned place preference in rats.

    PubMed

    Gehrke, B J; Harrod, S B; Cass, W A; Bardo, M T

    2003-03-01

    Methamphetamine has been shown to produce neurotoxicity demonstrated by depletions of dopamine and serotonin in the striatum and nucleus accumbens. The current study examined the effects of neurotoxic doses of methamphetamine on the rewarding effect of subsequent administration of methamphetamine assessed by the conditioned place preference (CPP) procedure. Male and female rats were treated with a neurotoxic regimen of methamphetamine (4 x 10 mg/kg, s.c., once every 2 h) or saline, and concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid were measured 15 days later in the striatum, nucleus accumbens, and prefrontal cortex (PFC). In another experiment, male rats were given methamphetamine neurotoxic treatment or saline and were then conditioned 7 days later with methamphetamine (0.1, 0.3, or 1.0 mg/kg, s.c.) or saline using a four-trial CPP procedure. Locomotor activity was also measured during the conditioning sessions to investigate whether or not the neurotoxic methamphetamine treatment altered locomotor activity following a subsequent methamphetamine challenge. Males and females did not differ significantly in the amount of neurochemical depletion produced by methamphetamine in any brain region. Collapsed across sex, dopamine was significantly depleted in nucleus accumbens (25%) and striatum (51%); serotonin was significantly depleted in nucleus accumbens (35%), striatum (34%) and PFC (33%). The methamphetamine challenge dose dependently increased locomotor activity, but the increase was not affected by treatment with neurotoxic doses of methamphetamine. In contrast, treatment with neurotoxic doses of methamphetamine enhanced CPP at the intermediate conditioning dose (0.3 mg/kg). These results indicate that the rewarding effect of methamphetamine is enhanced by prior treatment with neurotoxic doses of methamphetamine, suggesting either a compensatory hyperfunctioning of spared dopamine neurons or a loss of

  8. "Meth mouth": rampant caries in methamphetamine abusers.

    PubMed

    Shaner, J W; Kimmes, N; Saini, T; Edwards, P

    2006-03-01

    Rampant dental caries is a characteristic finding in methamphetamine abusers. The popularity of methamphetamine, particularly among the gay community where it is linked to the spread of HIV, its ready availability, and rapid spread across the nation have placed methamphetamine use in an epidemic status in many communities unaccustomed to dealing with drug abuse. We present a case of a 25-year-old male "meth" abuser of unknown HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) status to promote recognition by the health care team of the association of rampant dental caries with methamphetamine abuse for appropriate intervention to ensure successful treatment and prevention of disease progression.

  9. Enzyme immunoassay for methamphetamine.

    PubMed

    Aoki, K; Kuroiwa, Y

    1983-01-01

    A competitive enzyme immunoassay for methamphetamine with alkaline phosphatase labeled methamphetamine, Sepharose-antibody and p-nitrophenylphosphate as substrate was developed. The anti-methamphetamine antisera produced in rabbits by immunization with N-(4-aminobutyl) methamphetamine-BSA conjugate were specific for methamphetamine and showed low cross-reactivities with p-OH methamphetamine and amphetamine (metabolites of methamphetamine). The range of methamphetamine measurable by the enzyme immunoassay was 1 to 300 ng/tube. According to the assay, methamphetamine could be detected from urine and extract of hair.

  10. Mind Over Matter: Methamphetamine

    MedlinePlus

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

  11. Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

    PubMed

    Kuiper, Lindsey B; Frohmader, Karla S; Coolen, Lique M

    2017-09-01

    The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior in male rats and the effects of concurrent Meth and sexual behavior on neural activity, using ERK phosphorylation (pERK). First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm increased pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala. Second, effects of concurrent Meth and sex experience were tested in males that were exposed to four daily sessions of concurrent Meth (1 mg/kg) or saline and mating and subsequently exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment of inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC. These alterations of pERK occurred in CaMKII-expressing neurons, suggesting changes in efferent projections of these areas. Altogether, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.

  12. Methamphetamine (Meth)

    MedlinePlus

    ... with dopamine, depleting its supply. So, once the effects have warn off, the brain will no longer send the small amounts of this pleasure producing chemical to the brain when you do ordinary activities, and that can lead to depression. Regular use of methamphetamine causes chemical and molecular ...

  13. Steep effort discounting of a preferred reward over a freely-available option in prolonged methamphetamine withdrawal in male rats.

    PubMed

    Thompson, Andrew B; Gerson, Julian; Stolyarova, Alexandra; Bugarin, Amador; Hart, Evan E; Jentsch, J David; Izquierdo, Alicia

    2017-06-06

    Drug addiction can be described as aberrant allocation of effort toward acquiring drug, despite associated costs. It is unclear if this behavioral pattern results from an overvaluation of reward or to an altered sensitivity to costs. Present experiments assessed reward sensitivity and effortful choice in rats following 1 week of withdrawal from methamphetamine (mAMPH). Rats were treated with either saline or an escalating dose mAMPH regimen, then tested after a week without the drug. In experiment 1, rats were given a free choice between water and various concentrations of sucrose solution to assess general reward sensitivity. In experiment 2, rats were presented with a choice between lever-pressing for sucrose pellets on a progressive ratio schedule or consuming freely-available chow. In experiment 1, we found no differences in sucrose preference between mAMPH- and saline-pretreated rats. In experiment 2, when selecting between two options, mAMPH-pretreated rats engaged in less lever-pressing for sucrose pellets (p < 0.01) and switched from this preferred reward to the chow sooner than saline-pretreated rats (p < 0.05). This effect was not consistent with general reward devaluation or loss of motivation. These findings demonstrate that mAMPH exposure and withdrawal lead to steeper discounting of reward value by effort, an effect that is consistent with the effect of mAMPH on discounting by delay, and which may reflect an underlying shared mechanism.

  14. Depression and alterations in hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axis function in male abstinent methamphetamine abusers.

    PubMed

    Li, Su-Xia; Yan, Shi-Yan; Bao, Yan-Ping; Lian, Zhi; Qu, Zhi; Wu, Ya-Ping; Liu, Zhi-Min

    2013-09-01

    The present study was to investigate depression and alterations in the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis function in methamphetamine (METH) abusers after abstinence. Depression was assessed using the 13-item Beck Depression Inventory (BDI-13) scale; blood samples from in-patients who were METH abusers and age-matched and sex-matched healthy controls were collected. The demographic characteristics and history of METH abuse also was assessed. We found that serum levels of adrenocorticotropic hormone (ACTH) and thyroxine were increased; and serum levels of cortisol, triiodothyronine, and thyroid-stimulating hormone were decreased; and the BDI score was higher in METH abusers compared with control. In addition, there was no correlation between the BDI-13 score and any of hormones of HPA and HPT axis was found. Particularly, we found abnormally higher ACTH level and mismatched with lower cortisol level in abstinent METH abusers. These results indicate that METH abusers and that their HPA and HPT functions are all altered after abstinence. Chronically using METH may destroy the regulatory function of the HPA axis, especially the feedback regulation of cortisol to ACTH. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Sex differences in methamphetamine toxicity in mice: effect on brain dopamine signaling pathways.

    PubMed

    Bourque, Mélanie; Liu, Bin; Dluzen, Dean E; Di Paolo, Thérèse

    2011-08-01

    Male mice were reported to display greater methamphetamine-induced neurotoxicity than females. The present study evaluated the involvement of phosphatidylinositol-3 kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK1/2) pathways in this sex-dependent methamphetamine toxicity. Intact female and male mice were administered methamphetamine (20 or 40mg/kg) and euthanized a week later. Dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) autoradiography in the lateral striatum showed a greater sensitivity in male mice treated with 20mg/kg methamphetamine compared to female mice. Striatal dopamine concentration and DAT autoradiography showed a more extensive depletion in male mice given 40mg/kg methamphetamine compared to female mice. Mice administered 40mg/kg methamphetamine showed no sex difference in striatal VMAT2 autoradiography. In the substantia nigra, DAT specific binding was decreased only in male mice treated with 40mg/kg methamphetamine and DAT mRNA levels decreased in methamphetamine-treated female and male mice. Methamphetamine-treated male mice presented a dose-dependent decrease of VMAT2 mRNA levels. Methamphetamine reduced insulin-like growth factor 1 receptor levels in females at both methamphetamine doses tested whereas it elevated G protein-coupled estrogen receptor 1 (GPER1) only in male mice. Phosphorylated Akt levels decreased only in male mice treated with 40mg/kg methamphetamine. Glycogen synthase kinase 3β levels were reduced in male mice at both methamphetamine doses tested and in females receiving 40mg/kg. Bcl-2 levels were increased in male mice treated with methamphetamine, whereas ERK1/2 and BAD levels were unchanged. These results implicate some of the signaling pathways associated with the sex differences in methamphetamine-induced toxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Delayed emergence of methamphetamine's enhanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence.

    PubMed

    Vaupel, D B; Schindler, C W; Chefer, S; Belcher, A M; Ahmet, I; Scheidweiler, K B; Huestis, M A; Stein, E A

    2016-02-01

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

  17. Correlates of shared methamphetamine injection among methamphetamine-injecting treatment seekers: the first report from Iran.

    PubMed

    Mehrjerdi, Zahra Alam; Abarashi, Zohreh; Noroozi, Alireza; Arshad, Leila; Zarghami, Mehran

    2014-05-01

    Shared methamphetamine injection is an emerging route of drug use among Iranian methamphetamine injectors. It is a primary vector for blood-borne infections. The aim of the current study is to determine the prevalence and correlates of shared methamphetamine injection in a sample of Iranian methamphetamine injecting treatment seekers in the south of Tehran. We surveyed male and female methamphetamine injectors at three drop-in centres and 18 drug-use community treatment programmes. Participants reported socio-demographic characteristics, drug use, high-risk behaviours, current status of viral infections and service use for drug treatment. Bivariate and multivariate logistic regression models were used to test associations between participants' characteristics and shared methamphetamine injection. Overall, 209 clients were recruited; 90.9% were male; 52.6% reported current methamphetamine injection without any shared injection behaviour and 47.4% reported current shared methamphetamine injection. Shared methamphetamine injection was found to be primarily associated with living with sex partners (AOR 1.25, 95% CI 1.13-1.98), reporting ≥3 years of dependence on methamphetamine injection (AOR 1.61, 95% CI 1.27-2.12), injection with pre-filled syringes in the past 12 months (AOR 1.96, 95% CI 1.47-2.42), homosexual sex without condom use in the past 12 months (AOR 1.85, 95% CI 1.21-2.25), the paucity of NA group participation in the past 12 months (AOR 0.67, 95% CI 0.41-0.99), the paucity of attending psychotherapeutic sessions in the past 12 months (AOR 0.44, 95% CI 0.28-0.96) and positive hepatitis C status (AOR 1.98, 95% CI 1.67-2.83). Deeper exploration of the relationship between shared methamphetamine injection and sexual risk among Iranian methamphetamine injectors would benefit HIV/sexually transmitted infection prevention efforts. In addition, existing psychosocial interventions for methamphetamine-injecting population may need to be adapted to better meet the

  18. 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

  19. Role of d-amphetamine and d-methamphetamine as active metabolites of benzphetamine: Evidence from drug discrimination and pharmacokinetic studies in male rhesus monkeys.

    PubMed

    Banks, Matthew L; Snyder, Rodney W; Fennell, Timothy R; Negus, S Stevens

    2017-05-01

    Benzphetamine is a Schedule III anorectic agent that is a prodrug for d-amphetamine and d-methamphetamine and may have utility as an "agonist" medication for cocaine use disorder treatment. This study evaluated the pharmacokinetic-pharmacodynamic profile of benzphetamine using a drug discrimination procedure in rhesus monkeys. The potency and time course of cocaine-like discriminative stimulus effects were compared for benzphetamine (10-18mg/kg, intramuscular (IM)) and d-amphetamine (0.032-0.32mg/kg, IM) in monkeys (n=3-4) trained to discriminate IM cocaine (0.32mg/kg) from saline in a two-key food-reinforced discrimination procedure. Parallel pharmacokinetic studies in the same monkeys determined plasma benzphetamine, d-methamphetamine and/or d-amphetamine levels for correlation with behavioral effects. d-Amphetamine produced dose-dependent, time-dependent, and full cocaine-like effects, i.e. ≥90% cocaine-appropriate responding, in all monkeys without altering response rates. The time course of d-amphetamine's cocaine-like discriminative stimulus effects correlated with plasma d-amphetamine levels. Benzphetamine was 180-fold less potent than d-amphetamine and produced full cocaine-like effects in only 2 of 4 monkeys while significantly decreasing response rates. Benzphetamine administration increased plasma d-methamphetamine (peak at 100min) and d-amphetamine (peak at 24h) levels, but the time course of behavioral effects did not correlate with increased levels of benzphetamine, d-methamphetamine or d-amphetamine. These results suggest that benzphetamine yields d-amphetamine and d-methamphetamine as active metabolites in rhesus monkeys, but generation of these metabolites is not sufficient to account for benzphetamine behavioral effects. The incomplete cocaine substitution profile and protracted d-amphetamine plasma levels suggest that benzphetamine may still warrant further evaluation as a candidate pharmacotherapy for cocaine use disorder treatment. Copyright

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

    PubMed Central

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

    2016-01-01

    Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 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. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Methamphetamine Use and Pulmonary Hypertension

    MedlinePlus

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

  3. Initiation into methamphetamine use for young gay and bisexual men.

    PubMed

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

    2007-10-08

    Research over the past 10 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.

  4. Nicotine elicits methamphetamine-seeking in rats previously administered nicotine.

    PubMed

    Neugebauer, N M; Harrod, S B; Bardo, M T

    2010-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  5. Nicotine Elicits Methamphetamine-Seeking in Rats Previously Administered Nicotine

    PubMed Central

    Neugebauer, N. M.; Harrod, S. B.; Bardo, M. T.

    2009-01-01

    Research has indicated a high correlation between psychostimulant use and tobacco cigarette smoking in human substance abusers. The objective of the current study was to examine the effects of acute and repeated nicotine administration on responding for intravenous methamphetamine (0.03 mg/kg/infusion) in a rodent model of self-administration, as well as the potential of nicotine to induce reinstatement of previously extinguished drug-taking behavior in male Sprague-Dawley rats. In addition, it was assessed whether nicotine-induced reinstatement of methamphetamine-seeking behavior and nicotine-induced locomotor sensitization require that nicotine be temporally paired with the methamphetamine self-administration session or the locomotor activity chamber. Nicotine acutely decreased methamphetamine self-administration, but did not persistently alter responding during the maintenance of methamphetamine self-administration. However, following extinction of methamphetamine self-administration, nicotine administration reinstated methamphetamine-seeking behavior only in rats that had previously been administered nicotine. Nicotine-induced reinstatement and expression of locomotor sensitization were not dependent on a temporal pairing of nicotine with either the methamphetamine self-administration session or the locomotor activity chamber, respectively. These results indicate that nicotine may be acting, at least in part, through a non-associative mechanism to reinstate methamphetamine-seeking behavior. PMID:19733448

  6. 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

  7. Crystal methamphetamine initiation among street-involved youth.

    PubMed

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

    2014-01-01

    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. Our objectives were to examine rates and risk factors for the initiation of crystal methamphetamine use in a cohort of street-involved youth. 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. 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]). 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.

  8. Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats.

    PubMed

    Byrnes-Blake, Kelly A; Laurenzana, Elizabeth M; Carroll, F Ivy; Abraham, Philip; Gentry, W Brooks; Landes, Reid D; Owens, S Michael

    2003-02-14

    Our studies examined pharmacokinetic mechanisms involved in high-affinity (K(d) approximately 11 nM) monoclonal antibody-based antagonism of (+)-methamphetamine-induced locomotor effects. Male rats received (+)-methamphetamine (0.3, 1, or 3 mg/kg i.v.) followed 30 min later by saline or anti-(+)-methamphetamine monoclonal antibody. All groups received a constant dose of monoclonal antibody that was equimolar in binding sites to the body burden of a 1 mg/kg i.v. (+)-methamphetamine dose 30 min after administration. The monoclonal antibody antagonized locomotor effects due to 0.3 and 1 mg/kg (+)-methamphetamine. In contrast, monoclonal antibody treatment increased locomotor activity due to 3 mg/kg (+)-methamphetamine. We also investigated the serum and brain pharmacokinetics of (+)-methamphetamine without and with the monoclonal antibody. Rats received (+)-methamphetamine (1 mg/kg i.v.) followed by saline or monoclonal antibody treatment at 30 min. The monoclonal antibody significantly increased serum methamphetamine concentrations and significantly decreased brain methamphetamine concentrations. These data indicate that anti-(+)-methamphetamine monoclonal antibody-induced pharmacodynamics are complex, but are related to time-dependent changes in (+)-methamphetamine brain distribution. Copyright 2003 Elsevier Science B.V.

  9. 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. © 2012 The

  10. 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

  11. Methamphetamine abuse and dentistry.

    PubMed

    Hamamoto, D T; Rhodus, N L

    2009-01-01

    Methamphetamine is a highly addictive powerful stimulant that increases wakefulness and physical activity and produces other effects including cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. The prevalence of methamphetamine use is estimated at 35 million people worldwide and 10.4 million people in the United States. In the United States, the prevalence of methamphetamine use is beginning to decline but methamphetamine trafficking and use are still significant problems. Dental patients who abuse methamphetamine can present with poor oral hygiene, xerostomia, rampant caries ('Meth mouth'), and excessive tooth wear. Dental management of methamphetamine users requires obtaining a thorough medical history and performing a careful oral examination. The most important factor in treating the oral effects of methamphetamine is for the patient to stop using the drug. Continued abuse will make it difficult to increase salivary flow and hinder the patient's ability to improve nutrition and oral hygiene. Local anesthetics with vasoconstrictors should be used with care in patients taking methamphetamine because they may result in cardiac dysrhythmias, myocardial infarction, and cerebrovascular accidents. Thus, dental management of patients who use methamphetamine can be challenging. Dentists need to be aware of the clinical presentation and medical risks presented by these patients.

  12. 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

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

    PubMed

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

    2015-07-11

    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. 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. 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. 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 novel object recognition deficits are

  14. Methamphetamine-related emergency department utilization and cost.

    PubMed

    Hendrickson, Robert G; Cloutier, Robert; McConnell, K John

    2008-01-01

    To quantify the frequency, cost, and characteristics associated with emergency department (ED) visits that are related to methamphetamine use. This was a prospective observational study. The authors performed a training program for ED clinicians on the acute and chronic effects of methamphetamine and the signs of methamphetamine abuse. A standardized two question survey was administered to clinicians concerning the relationship between the ED visit and the patient's methamphetamine use. The survey was embedded in the patient tracking system and was required for all ED patients before disposition. Survey results were merged with administrative data on demographics, diagnosis, disposition, and charges. Univariate analyses were used to determine patient characteristics associated with methamphetamine-related ED visits. The authors examined 15,038 ED visits over a 20-week period from February 2006 to June 2006. There were a total of 353 methamphetamine-related visits, for an average of 17.65 visits per week (2.4% of all visits). Hospital charges for methamphetamine-related ED visits averaged $133,181 per week, for an estimated total of $6.9 M in annual charges. Methamphetamine-related ED patients were more likely to be male (odds ratio [OR] 1.6, 95% confidence interval [CI] = 1.30 to 2.01), white (OR 1.8, 95% CI = 1.38 to 2.29), and uninsured (OR 3.2, 95% CI = 2.21 to 4.69). The top four medical conditions associated with methamphetamine-related visits were mental health (18.7%), trauma (18.4%), skin infections (11.1%), and dental diagnoses (9.6%). Methamphetamine abuse accounts for a modest but substantial proportion of ED utilization and hospital cost. Methamphetamine-related ED visits are most commonly related to mental illness, trauma, skin, and dental-related problems.

  15. mGluR5 antagonism attenuates methamphetamine reinforcement and prevents reinstatement of methamphetamine-seeking behavior in rats.

    PubMed

    Gass, Justin T; Osborne, Megan P H; Watson, Noreen L; Brown, Jordan L; Olive, M Foster

    2009-03-01

    Addiction to methamphetamine is a significant public health problem, and there are currently no pharmacological agents that are approved for the treatment of addiction to this powerful psychostimulant. Chronic methamphetamine use leads to cognitive dysfunction as well as numerous psychiatric, neurological, and cardiovascular complications. There is a growing body of literature implicating an important role for glutamate neurotransmission in psychostimulant addiction. In the present study, we examined the effects of the selective type 5 metabotropic glutamate receptor (mGluR5) antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) on intravenous self-administration of methamphetamine and reinstatement of methamphetamine-seeking behavior. Adult male Sprague-Dawley rats were trained to respond for intravenous methamphetamine (0.1 or 0.2 mg/kg per infusion) or food pellets and were subsequently administered vehicle or MTEP (0.3-3 mg/kg) before drug or food self-administration on a fixed-ratio 1 (FR1) schedule of reinforcement or a progressive ratio (PR) schedule of reinforcement. We also examined the effects of vehicle or MTEP (0.3-3 mg/kg) on cue- and drug-induced reinstatement of methamphetamine-seeking behavior as well as cue-induced reinstatement of food-seeking behavior. Our results show that MTEP dose dependently reduced the reinforcing effects of methamphetamine under FR1 and PR schedules of reinforcement without altering overall responding for food. MTEP also dose dependently prevented cue- and drug-induced reinstatement of methamphetamine-seeking behavior, but did not alter cue-induced reinstatement of food-seeking behavior. Together, these results indicate that mGluR5 receptors mediate methamphetamine reinforcement and methamphetamine-seeking behavior, and that pharmacological inhibitors of mGluR5 receptor function may represent a novel class of potential therapeutic agents for the treatment of methamphetamine addiction.

  16. mGluR5 antagonism attenuates methamphetamine reinforcement and prevents reinstatement of methamphetamine-seeking behavior in rats

    PubMed Central

    Gass, Justin T.; Osborne, Megan P.H.; Watson, Noreen L.; Brown, Jordan L.; Olive, M. Foster

    2009-01-01

    Addiction to methamphetamine is a significant public health problem, and there are currently no pharmacological agents that are approved for the treatment of addiction to this powerful psychostimulant. Chronic methamphetamine use leads to cognitive dysfunction as well as numerous psychiatric, neurological, and cardiovascular complications. There is a growing body of literature implicating an important role for glutamate neurotransmission in psychostimulant addiction. In the present study, we examined the effects of the selective type 5 metabotropic glutamate receptor (mGluR5) antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) on intravenous self-administration of methamphetamine and reinstatement of methamphetamine-seeking behavior. Adult male Sprague-Dawley rats were trained to respond for intravenous methamphetamine (0.1 or 0.2 mg/kg/infusion) or food pellets and were subsequently administered vehicle or MTEP (0.3-3 mg/kg) prior to drug or food self-administration on a fixed-ratio 1 (FR1) schedule of reinforcement or a progressive ratio (PR) schedule of reinforcement. We also examined the effects of vehicle or MTEP (0.3-3 mg/kg) on cue- and drug-induced reinstatement of methamphetamine-seeking behavior as well as cue-induced reinstatement of food-seeking behavior. Our results show that MTEP dose-dependently reduced the reinforcing effects of methamphetamine under an FR1 and PR schedule of reinforcement without altering overall responding for food. MTEP also dose-dependently prevented cue and drug-induced reinstatement of methamphetamine-seeking behavior, but did not alter cue-induced reinstatement of food-seeking behavior. Together, these results indicate the mGluR5 receptors play an important role in methamphetamine reinforcement and methamphetamine-seeking behavior, and that pharmacological inhibitors of mGluR5 receptor function may represent a novel class of potential therapeutic agents for the treatment of methamphetamine addiction. PMID

  17. Effects of circadian disruption on methamphetamine consumption in methamphetamine-exposed rats.

    PubMed

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

    2015-06-01

    A substantial number of clinical studies indicate associations between sleep abnormalities and drug abuse; however, the role played by the circadian system in the development of addiction is largely unknown. The aim of this study was to examine the effects of experimentally induced chronic jet lag on methamphetamine consumption in a rat model of methamphetamine drinking. Male Sprague-Dawley rats (n = 32) were housed in running wheel cages in a 12:12 h light:dark cycle. One group of rats (n = 16) was given 2 weeks of forced methamphetamine consumption (0.01 % in drinking water; meth pre-exposed) while a second group (n = 16, not pre-exposed) received water only. This was followed by a 2-week abstinence period during which half of the animals from each group were exposed to four consecutive 6-h advancing phase shifts of the light:dark cycle, while the other half remained on the original light:dark cycle. Methamphetamine consumption was assessed in all rats following the deprivation period using a two-bottle choice paradigm. Methamphetamine consumption was initially lower in methamphetamine pre-exposed versus not pre-exposed rats. However, during the second week following abstinence, consumption was significantly higher in phase-shifted rats of the methamphetamine pre-exposed group compared to all other groups. These data reveal an effect of circadian rhythm disturbance on methamphetamine consumption and suggest that dysregulation of the circadian system be considered in the etiology of relapse and addiction.

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

    PubMed Central

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

    2015-01-01

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

  19. Chronic stress augments the long-term and acute effects of methamphetamine.

    PubMed

    Matuszewich, L; Yamamoto, B K

    2004-01-01

    There is growing evidence that exposure to stress alters the acute effects of abused drugs on the CNS. However, it is not known whether stress augments the longer-term neurotoxic effects of psychostimulant drugs, such as methamphetamine. Methamphetamine at high doses decreases forebrain dopamine concentrations. The current study tested the hypothesis that 10 days of unpredictable stress augmented striatal dopamine depletions 7 days following four injections of either 7.5 or 10 mg/kg methamphetamine (1 injection every 2 h). Furthermore, to assess the effects of chronic stress on immediate responses to methamphetamine, extracellular striatal dopamine and methamphetamine concentrations, and rectal temperature were monitored during the methamphetamine injection regimen. Seven days following either a 7.5 mg/kg or 10 mg/kg methamphetamine injection regimen, male rats exposed to unpredictable stress showed greater depletions in striatal dopamine tissue content compared with non-stressed controls injected with methamphetamine. Stressed rats had increased hyperthermic responses and dopamine efflux in the striatum during the methamphetamine injections when compared with non-stressed control rats. Moreover, stressed rats had an increased mortality rate (33%) compared with non-stressed controls (16.7%) following four injections of 10 mg/kg methamphetamine. The enhanced acute and longer-term effects of methamphetamine in stressed rats was not due to a greater concentrations of methamphetamine in the striatum, as extracellular levels of methamphetamine during the injection regimen did not differ between the two groups. In summary, exposure to 10 days of chronic unpredictable stress augments longer-term depletions of dopamine in the striatum, as well as acute methamphetamine-induced hyperthermia and extracellular dopamine levels. These findings suggest that chronic stress increases the responsiveness of the brain to the acute pharmacological effects of methamphetamine and

  20. Methamphetamine-Associated Cardiomyopathy

    PubMed Central

    Won, Sekon; Hong, Robert A.; Shohet, Ralph V.; Seto, Todd B.; Parikh, Nisha I.

    2015-01-01

    Methamphetamine and related compounds are now the second most commonly used illicit substance worldwide, after cannabis. Reports of methamphetamine-associated cardiomyopathy (MAC) are increasing, but MAC has not been well reviewed. This analysis of MAC will provide an overview of the pharmacology of methamphetamine, historical perspective and epidemiology, a review of case and clinical studies, and a summary of the proposed mechanisms for MAC. Clinically, many questions remain, including the appropriate therapeutic interventions for MAC, the incidence and prevalence of cardiac pathology in methamphetamine users, risk factors for developing MAC, and prognosis of these patients. In conclusion, recognition of the significance of MAC among physicians and other medical caregivers is important given the growing use of methamphetamine and related stimulants worldwide. PMID:24037954

  1. Neurotoxic effects of methamphetamine.

    PubMed

    Thrash, Bessy; Karuppagounder, Senthilkumar S; Uthayathas, Subramaniam; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

    2010-01-01

    In Parkinson's disease, depletion of dopamine in the striatum leads to various symptoms such as tremor, rigidity and akinesia. Methamphetamine use has significantly increased in USA and around the world and there are several reports showing that its long-term use increases the risk for dopamine depletion. However, the toxic mechanisms of methamphetamine are not well understood. This study was undertaken to gain greater mechanistic understanding of the toxicity induced by methamphetamine. We evaluated the effect of methamphetamine on the generation of reactive oxygen species, mitochondrial monoamine oxidase, complex I & IV activities. Behavioral analysis evaluated the effect on catalepsy, akinesia and swim score. Neurotransmitter levels were evaluated using high pressure liquid chromatography (HPLC) electrochemical detection (ECD). Results showed that methamphetamine caused significant generation of reactive oxygen species and decreased complex I activity in the mitochondria leading to dopamine depletion in the striatum.

  2. Long-term effects of neonatal methamphetamine exposure on cognitive function in adolescent mice.

    PubMed

    Siegel, Jessica A; Park, Byung S; Raber, Jacob

    2011-05-16

    Exposure to methamphetamine during brain development impairs cognition in children and adult rodents. In mice, these impairments are greater in females than males. Adult female, but not male, mice show impairments in novel location recognition following methamphetamine exposure during brain development. In contrast to adulthood, little is known about the potential effects of methamphetamine exposure on cognition in adolescent mice. As adolescence is an important time of development and is relatively understudied, the aim of the current study was to examine potential long-term effects of neonatal methamphetamine exposure on behavior and cognition during adolescence. Male and female mice were exposed to methamphetamine (5 mg/kg) or saline once a day from postnatal days 11 to 20, the period of rodent hippocampal development. Behavioral and cognitive function was assessed during adolescence beginning on postnatal day 30. During the injection period, methamphetamine-exposed mice gained less weight on average compared to saline-exposed mice. In both male and female mice, methamphetamine exposure significantly impaired novel object recognition and there was a trend toward impaired novel location recognition. Anxiety-like behavior, sensorimotor gating, and contextual and cued fear conditioning were not affected by methamphetamine exposure. Thus, neonatal methamphetamine exposure affects cognition in adolescence and unlike in adulthood equally affects male and female mice.

  3. Long-Term Effects of Neonatal Methamphetamine Exposure on Cognitive Function in Adolescent Mice

    PubMed Central

    Siegel, Jessica A.; Park, Byung S.; Raber, Jacob

    2011-01-01

    Exposure to methamphetamine during brain development impairs cognition in children and adult rodents. In mice, these impairments are greater in females than males. Adult female, but not male, mice show impairments in novel location recognition following methamphetamine exposure during brain development. In contrast to adulthood, little is known about the potential effects of methamphetamine exposure on cognition in adolescent mice. As adolescence is an important time of development and is relatively understudied, the aim of the current study was to examine potential long-term effects of neonatal methamphetamine exposure on behavior and cognition during adolescence. Male and female mice were exposed to methamphetamine (5 mg/kg) or saline once a day from postnatal day 11-20, the period of rodent hippocampal development. Behavioral and cognitive function was assessed during adolescence beginning on postnatal day 30. During the injection period, methamphetamine-exposed mice gained less weight on average compared to saline-exposed mice. In both male and female mice, methamphetamine exposure significantly impaired novel object recognition and there was a trend towards impaired novel location recognition. Anxiety-like behavior, sensorimotor gating, and contextual and cued fear conditioning were not affected by methamphetamine exposure. Thus, neonatal methamphetamine exposure affects cognition in adolescence and unlike in adulthood equally affects male and female mice. PMID:21238498

  4. Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and behavior in adult offspring.

    PubMed

    Bubenikova-Valesova, Vera; Kacer, Petr; Syslova, Kamila; Rambousek, Lukas; Janovsky, Martin; Schutova, Barbora; Hruba, Lenka; Slamberova, Romana

    2009-10-01

    Methamphetamine is a commonly abused psychostimulant that causes addiction and is often abused by pregnant women. Acute or chronic administration of methamphetamine elevates the levels of the extracellular monoamine neurotransmitters, such as dopamine. The aim of the present study was to show whether prenatal exposure to methamphetamine (5mg/kg, entire gestation) or saline in Wistar rats induces changes in dopamine levels and its metabolites in the nucleus accumbens, and in behavior (locomotor activity, rearing, and immobility) after the administration of a challenge dose of methamphetamine (1mg/kg) or saline in male offspring. We found that adult offspring prenatally exposed to methamphetamine had higher basal levels of dopamine (about 288%), dihydroxyphenylacetic acid (about 67%) and homovanillic acid (about 74%) in nucleus accumbens. An increased basal level of dopamine corresponds to lower basal immobility in offspring prenatally exposed to methamphetamine. The acute injection of methamphetamine in adulthood increased the level of dopamine in the nucleus accumbens, which is related to an increase of locomotion and rearing (exploration). In addition, prenatally methamphetamine-exposed rats showed higher response to the challenge dose of methamphetamine, when compared to prenatally saline-exposed rats. In conclusion, rats exposed to methamphetamine in utero have shown changes in the mesolimbic dopaminergic system and were more sensitive to the administration of the acute dose of methamphetamine in adulthood.

  5. Sex and temporally-dependent effects of methamphetamine toxicity on dopamine markers and signaling pathways.

    PubMed

    Bourque, Mélanie; Dluzen, Dean E; Di Paolo, Thérèse

    2012-06-01

    Methamphetamine induces a greater neurodegenerative effect in male versus female mice. In order to investigate this sex difference we studied the involvement of Akt and extracellular signal-regulated kinase (ERK1/2) in methamphetamine toxicity as a function of time post-treatment (30 min, 1 and 3 days). Methamphetamine-induced decreases in dopamine concentrations and dopamine transporter (DAT) specific binding in the medial striatum were similar in female and male mice when evaluated 1 day post-methamphetamine (40 mg/kg). At 3 days post-methamphetamine, striatal dopamine concentration and DAT specific binding continued to decline in males, whereas females showed a recovery with increases in dopamine content and DAT specific binding in medial striatum at day 3 versus day 1 post-methamphetamine. The reduction in striatal vesicular monoamine transporter 2 specific binding observed at 1 and 3 days post-methamphetamine showed neither a sex- nor temporal-dependent effect. Under the present experimental conditions, methamphetamine treatments had modest effects on dopamine markers measured in the substantia nigra. Proteins assessed by Western blots showed similar reductions in both female and male mice for DAT proteins at 1 and 3 days post-methamphetamine. An increase in the phosphorylation of striatal Akt (after 1 day), glycogen synthase kinase 3β (at 1 and 3 days) and ERK1/2 (30 min post-methamphetamine) was only observed in females. Striatal glial fibrillary acidic protein levels were augmented in both females and males at 3 days post-methamphetamine. These results reveal some of the sex- and temporally-dependent effects of methamphetamine toxicity on dopaminergic markers and suggest some of the signaling pathways associated with these responses.

  6. Perinatal effect of methamphetamine on nociception in adult Wistar rats.

    PubMed

    Yamamotová, A; Hrubá, L; Schutová, B; Rokyta, R; Šlamberová, R

    2011-02-01

    Methamphetamine is a psychostimulant drug which causes the release of monoamine neurotransmitters. Although drugs of abuse are known to have analgesic effects, there is a lack of evidence regarding the effect of prenatal exposure to methamphetamine on nociception in adulthood. Adult Wistar rats whose mothers had received daily exposure to methamphetamine (5 mg/kg; s.c.) or saline, during gestation or gestation and lactation periods, were examined for: (1) gender differences in nociception; (2) an association between nociception and gross-motor behavior in the plantar test; (3) effects of cross-fostering on nociception; and (4) analgesic effects of an acute injection of methamphetamine (1 mg/kg s.c.). Nociception was tested using the plantar test on postnatal days 85-90. Prenatal methamphetamine increased sensitivity to pain on forelimbs (p<0.0001) and hind limbs (p<0.05) in females only. Prenatal methamphetamine treated male rats fostered by adoptive injection stressed mothers had higher sensitivity to pain than prenatally injection stressed rats fostered by methamphetamine treated mothers (p<0.05). Acute methamphetamine induced analgesia faster in prenatally methamphetamine exposed rats than in controls. In all groups, analgesia increased in the cranio-caudal direction (p<0.0001). From our behavioral data it can be concluded that exposure to methamphetamine during the prenatal period completely dissociates the relationship between nociception and intensity of overall behavior observed in intact animals in adulthood. Thus, our results indicate that perinatal exposure to psychostimulants may have long-term impact on several functions related to dopaminergic system. Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. 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

  8. 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

  9. Research Reports: Methamphetamine

    MedlinePlus

    ... memory loss, aggression, psychotic behavior, damage to the cardiovascular system, malnutrition, and severe dental problems. Methamphetamine abuse has also been shown to contribute to increased transmission of infectious diseases, such as hepatitis and HIV/AIDS. Beyond its ...

  10. Methamphetamine-associated burn injuries: a retrospective analysis.

    PubMed

    Danks, Roy R; Wibbenmeyer, Lucy A; Faucher, Lee D; Sihler, Kristen C; Kealey, G Patrick; Chang, Phyllis; Amelon, Marge; Lewis, Robert W

    2004-01-01

    Methamphetamine production and use has increased dramatically during the past 10 years. Methamphetamine production requires combining hazardous and volatile chemicals that expose the manufacturer to burn injuries from explosions and chemical spills. We sought to review the epidemiology of burn injuries in a rural burn center secondary to the use of amphetamine or methamphetamine and/or the manufacture of methamphetamine. Review of the records of 507 patients who were admitted to our burn unit from December 1, 1998, to December 31, 2001, revealed 34 patients who were involved in the use of amphetamines or methamphetamines and/or the manufacture of methamphetamine. Thirty-one patients tested positive for either amphetamine (n = 2) or methamphetamine (n = 29) on routine admission urine drug screens. Twenty of these patients were involved in the manufacture of methamphetamines. Three additional patients were identified as methamphetamine manufacturers but tested negative for the use of methamphetamines. The mean age of the study population was 31.88 +/- 7.65 years, with a male:female ratio of 10.3:1. The average burn size was 18.86 +/- 20.72, with the majority secondary to flame (n = 26). Patient burn admission histories were vague, and the patient's involvement in the manufacture of methamphetamine was often only later confirmed by media, the fire marshal, family members, or the patient. Fifteen patients showed the usual withdrawal pattern of agitation and hypersomnolence, with seven patients requiring detoxification with benzodiazepines. Two were admitted acutely to the psychiatric ward for uncontrollable agitation. Eighteen patients were offered chemical dependency treatment, and two completed therapy. There was one mortality. The mean cost per person was US 77,580 dollars (range, US 112 dollars - US 426,386 dollars). The increasing use of and manufacture of methamphetamine presents new challenges for the burn team because these patients can become violent and

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-08-01

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

  13. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

  14. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

  15. 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

  16. 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

  17. Enhanced upregulation of CRH mRNA expression in the nucleus accumbens of male rats after a second injection of methamphetamine given thirty days later.

    PubMed

    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.

  18. 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

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

    PubMed

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

    2010-10-01

    Exposure to methamphetamine during brain development impairs cognition in humans and rodents. In mice, these impairments are more severe 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 days 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.

  20. 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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Stoops, Thorne S; D'Souza, Manoranjan S

    2017-01-01

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

  3. 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

  4. Boundary Conditions of Methamphetamine Craving

    PubMed Central

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

    2015-01-01

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

  5. Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain

    PubMed Central

    Acevedo, Summer F.; Pfankuch, Timothy; van Meer, Peter; Raber, Jacob

    2011-01-01

    With the rise in methamphetamine use among women of childbearing age, the potential consequences of methamphetamine exposure to the developing brain for cognition in adulthood is a major concern. Histamine might mediate these methamphetamine effects. Following methamphetamine administration in neonatal mice, histamine levels in brain were elevated and the hypothalamic-pituitary-adrenal (HPA) axis was activated. Co-administration of methamphetamine with the H3 receptor agonist immepip antagonized these effects. The effects of methamphetamine on histamine levels and on HPA axis activation at P20 were more pronounced in female than male mice. These sex differences could have contributed to the increased susceptibility of female mice to the detrimental long-term cognitive effects of methamphetamine and the H3/H4 antagonist thioperamide. Following behavioral testing, mice neonatally treated with methamphetamine or thioperamide showed reduced levels of the dendritic marker microtubule-associated protein 2 in the CA3 region of the hippocampus and the enthorhinal cortex. This was not seen in mice neonatally treated with immepip and methamphetamine who did not show cognitive impairments, suggesting that these brain areas might be particularly important for the long-term effects of methamphetamine on cognitive function. These data support a role for histamine in the effects of methamphetamine on the developing brain. PMID:18786166

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

    PubMed

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

    2017-06-01

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

  7. Severe Aortic Stenosis Associated with Unicommissural Unicuspid Aortic Valve in a Middle Aged Male

    PubMed Central

    Kwon, Hee-Jin; Kim, Song Soo; Sun, Byung Joo; Jin, Sun Ah; Kim, Jun-Hyung; Lee, Jae-Hwan; Choi, Siwan; Jeong, Jin-Ok; Seong, In-Whan

    2016-01-01

    Unicuspid aortic valve (UAV) is an extremely rare form of congenital aortic valvular abnormality. Although UAV shows similar clinical characteristics to bicuspid aortic valve, the clinical symptoms develop at earlier age and progress at a faster pace in UAV. In this report, we are presenting a 42-year-old male with severe aortic stenosis associated with unicommissural UAV. The patients underwent a successful Bentall operation. PMID:27721957

  8. A Review of Treatment Options for Co-Occurring Methamphetamine Use Disorders and Depression

    PubMed Central

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

    2017-01-01

    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

  9. Ondansetron, a selective 5-HT3 antagonist, antagonizes methamphetamine-induced anorexia in mice.

    PubMed

    Ginawi, O T; Al-Majed, A A; Al-Suwailem, A K

    2005-03-01

    Effects of some selective serotonergic (5-HT) antagonists on methamphetamine-induced anorexia were investigated in male mice. The least possible dose of methamphetamine alone that caused significant anorectic activity was 11 micromolkg(-1), i.p. (2 mgkg(-1)). Various doses of some selective serotonergic receptor antagonists were administered half an hour before the above mentioned dose of methamphetamine. Methiothepin potentiated, whereas NAN-190, methysergide, mianserin and ondansetron antagonized methamphetamine-induced anorectic activity. The least possible doses of these antagonists which modified methamphetamine-induced anorexia were as follows: methiothepin (1.1 micromolkg(-1), i.p.), NAN-190 (4.2 micromolkg(-1), i.p.), methysergide (2.1 micromolkg(-1), i.p.), mianserin (3.3 micromolkg(-1), i.p.) and ondansetron (0.003 micromolkg(-1), i.p.). The serotonergic antagonists at the above mentioned doses did not modify the food intake of animals not treated with methamphetamine, except for methiothepin, which produced a significant reduction, and mianserin, which produced a significant increase in food intake. The results of the present study indicated that the anorectic activity induced by methamphetamine is related to the interactions of methamphetamine with 5-HT receptor. Since a very small dose (0.003 micromolkg(-1)) of ondansetron (the 5-HT(3) antagonist), as compared with the other antagonists used in this study, antagonized the anorexia induced by methamphetamine, the 5-HT(3) receptor is likely to be the site for this interaction.

  10. Transitioning illicit drug preferences and emerging user identities in Ohio: The proliferation of methamphetamine use among African Americans.

    PubMed

    Flynn, Karen Coen; Hoffer, Lee D

    2017-07-05

    Understanding the social dynamics of local methamphetamine markets is critical to improving community health and reducing social costs associated with illicit drug use. We examine a local drug market in Summit County, Ohio, wherein methamphetamine users ascribe themselves different ethnic identities from those long associated with the drug elsewhere in the United States. Qualitative interviews with 52 study participants demonstrate that very poor and homeless White males and females are now using methamphetamine; however, even more surprising is that 31 of the participants identified themselves as poor or homeless, male or female African, Native, biracial, or multiracial Americans. The drug use trajectory of these 31 participants in particular involved a transition from a historical preference for crack to a present one for methamphetamine and, in some cases, a preference for concurrent use of methamphetamine and heroin. Many of these methamphetamine users also emphasized their ethnic identity to distinguish themselves as nonproducers of methamphetamine in comparison to Whites, who are commonly associated with methamphetamine production. Findings appear to suggest an emergent means of identity management resulting from the ethnic diversity of users in this methamphetamine market. These findings may have relevance in other communities with similar demographics and drug markets and may hold important implications for drug treatment, policy-making, and law enforcement professionals' work associated with methamphetamine users, producers, and distributors.

  11. Methamphetamine use in a rural college population: associations with marijuana use, sensitivity to punishment, and sensitivity to reward.

    PubMed

    Simons, Jeffrey S; Dvorak, Robert D; Batien, Bryan D

    2008-09-01

    This study examined predictors of methamphetamine use in a 6-month prospective study of 2,270 rural young adults. Sensitivity to punishment (SP), sensitivity to reward (SR), and gender were exogenous variables in an observed variable path analysis with 3 endogenous criteria: Time 1 (T1) marijuana use and methamphetamine use at T1 and Time 2 (T2). SP was negatively associated with marijuana use at T1, and this association was attenuated by SR. Male gender was positively associated with marijuana use. T1 marijuana use and SR were positively, and male gender negatively, associated with T1 methamphetamine use. T1 methamphetamine use, T1 marijuana use, and SP were positively associated with T2 methamphetamine use. Methamphetamine use prevalence and the role of distal predictors and proximal indicators of drug involvement are discussed.

  12. The effect of d-methamphetamine on simulated driving performance.

    PubMed

    Silber, Beata Y; Croft, Rodney J; Downey, Luke A; Papafotiou, Katherine; Camfield, David A; Stough, Con

    2012-03-01

    Methamphetamine is considered to be one of the most popularly abused drugs by drivers; however, its exact effect on driving and driving behaviour has yet to be thoroughly investigated. This being despite methamphetamine's increased prevalence in injured and deceased drivers. Twenty healthy recreational illicit stimulant users (10 male and 10 female), aged between 21 and 32 years (mean = 25.4 years, SD = 3.3 years) attended two testing sessions involving oral consumption of 0.42 mg/kg d-methamphetamine or a matching placebo. The drug administration was counter-balanced, double-blind, and medically supervised. At each session driving, performance was assessed 2.5 h post drug administration. d-methamphetamine (0.42 mg/kg) did not significantly impair overall simulated driving performance 2.5 h post drug administration. At the individual driving variable level, participants in the d-methamphetamine condition were observed to be driving slower when an emergency situation occurred (T = 44, p < 0.05), but interestingly, participants in both conditions recorded average speeds in excess of the speed limit (100 km/h) when the emergency situations occurred. The d-methamphetamine condition did also produce four times more infringements where participants did not stop at red traffic light in comparison to the placebo, but this effect was only evident at a trend level (T = 7, p = 0.11). The findings presented herein suggest that d-methamphetamine administered at the levels supplied did not impair driving performance in a manner consistent with epidemiological evidence. Further research is certainly required to elucidate the effects of various doses of methamphetamine, alone and in combination with other legal and illicit substances. Copyright © 2012 John Wiley & Sons, Ltd.

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

    PubMed Central

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

    2015-01-01

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

  14. Methamphetamine exposure during brain development alters the brain acetylcholine system in adolescent mice.

    PubMed

    Siegel, Jessica A; Park, Byung S; Raber, Jacob

    2011-10-01

    Children exposed to methamphetamine during brain development as a result of maternal drug use have long-term hippocampus-dependent cognitive impairments, but the mechanisms underlying these impairments are not understood. The acetylcholine system plays an important role in cognitive function and potential methamphetamine-induced acetylcholine alterations may be related to methamphetamine-induced cognitive impairments. In this study, we investigated the potential long-term effects of methamphetamine exposure during hippocampal development on the acetylcholine system in adolescence mice on postnatal day 30 and in adult mice on postnatal day 90. Methamphetamine exposure increased the density of acetylcholine neurons in regions of the basal forebrain and the area occupied by acetylcholine axons in the hippocampus in adolescent female mice. In contrast, methamphetamine exposure did not affect the density of GABA cells or total neurons in the basal forebrain. Methamphetamine exposure also increased the number of muscarinic acetylcholine receptors in the hippocampus of adolescent male and female mice. Our results demonstrate for the first time that methamphetamine exposure during hippocampal development affects the acetylcholine system in adolescent mice and that these changes are more profound in females than males. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  15. Age and sex effects levels of choline compounds in the anterior cingulate cortex of adolescent methamphetamine users.

    PubMed

    Cloak, Christine C; Alicata, Daniel; Chang, Linda; Andrews-Shigaki, Brian; Ernst, Thomas

    2011-12-15

    Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug's impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations. Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13-23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed. FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show age-appropriate levels of ACC CHO. The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Age and sex effects levels of choline compounds in the anterior cingulate cortex of adolescent methamphetamine users

    PubMed Central

    Cloak, Christine C.; Alicata, Daniel; Chang, Linda; Andrews-Shigaki, Brian; Ernst, Thomas

    2011-01-01

    Background Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug’s impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations. Methods Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13–23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed. Results FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show showed age-appropriate levels of ACC CHO. Conclusions The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users. PMID:21775074

  17. Methamphetamine and Paranoia: The Methamphetamine Experience Questionnaire

    PubMed Central

    Leamon, Martin H.; Flower, Keith; Salo, Ruth E.; Nordahl, Thomas E.; Kranzler, Henry R.; Galloway, Gantt P.

    2011-01-01

    Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. METHODS: We administered the MEQ to 274 MA-dependent subjects. RESULTS: 45% (123) subjects first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = 0.77, p < 0.05 and kappa = 0.80, p < 0.05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the BSI paranoid ideation scale (rho = 0.27, p < 0.05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = 0.14, p = 0.07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. PMID:20163388

  18. Methamphetamine and paranoia: the methamphetamine experience questionnaire.

    PubMed

    Leamon, Martin H; Flower, Keith; Salo, Ruth E; Nordahl, Thomas E; Kranzler, Henry R; Galloway, Gantt P

    2010-01-01

    Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. We administered the MEQ to 274 MA-dependent subjects. Of the total subjects, 45% (123) first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = .77, p < .05 and kappa = .80, p < .05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the Brief Symptom Inventory (BSI) paranoid ideation scale (rho = .27, p < .05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = .14, p = .07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. (Am J Addict 2010;00:1-14).

  19. 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.

  20. Correlates of Trading Sex for Methamphetamine in a Sample of HIV-Negative Heterosexual Methamphetamine Users

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

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

    2017-07-20

    Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage. This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence. We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement. The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p < 0.001). The 8-OHdG levels did not alter after 2 weeks of methamphetamine abstinence (0.32 ± 0.12 ng/mL, p = 0.051 compared to baseline measurement; p = 0.12 compared to healthy controls). No significant correlations were observed between baseline 8-OHdG levels in methamphetamine users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use. Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.

  2. Parental methamphetamine abuse and children.

    PubMed

    McGuinness, Teena M; Pollack, Daniel

    2008-01-01

    Methamphetamine has alluring properties, such as the ability to promote weight loss and wakefulness, and because of its low price and ease of synthesis, methamphetamine abuse is now a nationwide problem in the United States. Unfortunately, the scope of the problem extends beyond adult users to the children of parents who are users. As methamphetamine abuse increases, the consequences of the epidemic pose major health and child welfare concerns. This article describes methamphetamine abuse and the long-term consequences of use, as well as specific nursing interventions to mitigate its effects.

  3. Neuroimmune Basis of Methamphetamine Toxicity

    PubMed Central

    Loftis, Jennifer M.; Janowsky, Aaron

    2015-01-01

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

  4. Neuroimmune basis of methamphetamine toxicity.

    PubMed

    Loftis, Jennifer M; Janowsky, Aaron

    2014-01-01

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

  5. Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals.

    PubMed

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

    2007-01-30

    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.

  6. 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.

  7. Methamphetamine psychosis: epidemiology and management.

    PubMed

    Glasner-Edwards, Suzette; Mooney, Larissa J

    2014-12-01

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

  8. Boundary conditions of methamphetamine craving.

    PubMed

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

    2015-12-01

    Methamphetamine use has increased significantly and become a global health concern. Craving is known to predict methamphetamine use and relapse following abstinence. Some have suggested that cravings are automatic, generalized, and uncontrollable, but experimental work addressing these claims is lacking. In 2 exploratory studies, we tested the boundary conditions of methamphetamine craving by asking: (a) is craving specific to users' preferred route of administration?, and (b) can craving be regulated by cognitive strategies? Two groups of methamphetamine users were recruited. In Study 1, participants were grouped by their preferred route of administration (intranasal vs. smoking), and rated their craving in response to photographs and movies depicting methamphetamine use (via the intranasal vs. smoking route). In Study 2, methamphetamine smokers implemented cognitive regulation strategies while viewing photographs depicting methamphetamine smoking. Strategies involved either focusing on the positive aspects of smoking methamphetamine or the negative consequences of doing so-the latter strategy based on treatment protocols for addiction. In Study 1, we found a significant interaction between group and route of administration, such that participants who preferred to smoke methamphetamine reported significantly stronger craving for smoking stimuli, whereas those who preferred the intranasal route reported stronger craving for intranasal stimuli. In Study 2, participants reported significantly lower craving when focusing on the negative consequences associated with methamphetamine use. Taken together, these findings suggest that strength of craving for methamphetamine is moderated by users' route of administration and can be reduced by cognitive strategies. This has important theoretical, methodological, and clinical implications. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  9. Methamphetamine Psychosis: Epidemiology and Management

    PubMed Central

    Glasner-Edwards, Suzette; Mooney, Larissa J.

    2016-01-01

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

  10. 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

    2015-04-05

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

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

    PubMed Central

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

    2015-01-01

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

  12. 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,…

  13. 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,…

  14. Red wine but not ethanol at low doses can protect against the toxicity of methamphetamine.

    PubMed

    Ali, Syed F; Bondy, S C

    2010-07-30

    The goal of this study was twofold: (a) to search for possible interactive effects between two common drugs of abuse, ethanol and methamphetamine. b) To inquire whether any effects of ethanol could be replicated using an equivalent amount of ethanol in the form of red wine. Adult male C57/6N mice received 2% ethanol for 8 weeks in drinking water or red wine diluted to yield the same ethanol content. On the 9th week animals received multiple injections of methamphetamine (4 x 10 mg/kg, ip, every 2 h). They were then sacrificed 72 h after treatment. Methamphetamine produced a significant depletion of dopamine and DOPAC in the striatum. Treatment with both ethanol and methamphetamine led to a reduction of striatal dopamine and DOPAC that were both non-significantly greater than that observed with methamphetamine alone. Alcohol alone produced no changes in the striatal content of dopamine or its metabolite, DOPAC. These data suggest that low doses of alcohol potentiate methamphetamine-induced neurotoxicity in mice and that this combination may be especially detrimental to the brain. However, an equivalent dose of ethanol in the form of red wine actually partially protected against methamphetamine-induced depletion of dopamine and DOPAC in red wine treated mice. This implies the presence of other agents in red wine, which may mitigate the toxicity of methamphetamine.

  15. 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

  16. Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine.

    PubMed

    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.

  17. Gender differences in the effect of tobacco use on brain phosphocreatine levels in methamphetamine-dependent subjects.

    PubMed

    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

    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 ease depression and improve cognitive performance in animals and humans. 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. Thirty female and 27 male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. 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. 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.

  18. Methamphetamine and the expanding complications of amphetamines.

    PubMed Central

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

    1999-01-01

    During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse. PMID:10344175

  19. Methamphetamine-related brainstem haemorrhage.

    PubMed

    Chiu, Zelia K; Bennett, Iwan E; Chan, Patrick; Rosenfeld, Jeffrey V

    2016-10-01

    We report the case of an otherwise healthy 29-year-old woman who presented with a brainstem haemorrhage following intravenous methamphetamine use. Extensive investigation did not reveal an underlying pathology, and the development of symptoms was temporally related to methamphetamine injection. Although intracerebral haemorrhage secondary to methamphetamine use is well documented, this report describes a haemorrhage within the brainstem which is a rare location. While animal studies have demonstrated the potential of methamphetamines to produce brainstem haemorrhages, there has only been one previous report describing a haemorrhage in this location due to amphetamine use in humans. We conclude with a brief discussion of the clinical features and aetiology of methamphetamine-related stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 on Abuse-Related Behavioral Indices of Methamphetamine in Rats

    PubMed Central

    Jing, Li; Zhang, Yanan

    2015-01-01

    Background: Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown. Methods: This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamine-induced behavioral sensitization, methamphetamine self-administration, cue- and methamphetamine-induced reinstatement of drug seeking, and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the trace amine associated receptor 1 agonist RO5263397 (3.2–10mg/kg). Results: RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue- and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors. However, RO5263397 did not alter cue-induced reinstatement of sucrose-seeking behavior. Conclusions: Taken together, trace amine associated receptor 1 agonists attenuate some abuse-related behavioral effects of methamphetamine, strongly suggesting that drugs activating trace amine associated receptor 1 may be potentially useful for the treatment of methamphetamine addiction and warrant further studies. PMID:25522401

  1. Effects of the trace amine associated receptor 1 agonist RO5263397 on abuse-related behavioral indices of methamphetamine in rats.

    PubMed

    Jing, Li; Zhang, Yanan; Li, Jun-Xu

    2014-10-31

    Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown. This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamine-induced behavioral sensitization, methamphetamine self-administration, cue- and methamphetamine-induced reinstatement of drug seeking, and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the trace amine associated receptor 1 agonist RO5263397 (3.2-10mg/kg). RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue- and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors. However, RO5263397 did not alter cue-induced reinstatement of sucrose-seeking behavior. Taken together, trace amine associated receptor 1 agonists attenuate some abuse-related behavioral effects of methamphetamine, strongly suggesting that drugs activating trace amine associated receptor 1 may be potentially useful for the treatment of methamphetamine addiction and warrant further studies. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  2. At the borders, on the edge: use of injected methamphetamine in Tijuana and Ciudad Juarez, Mexico.

    PubMed

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

    2008-02-01

    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

  3. 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

  4. Activation of mu opioid receptors in the striatum differentially augments methamphetamine-induced gene expression and enhances stereotypic behavior.

    PubMed

    Horner, Kristen A; Hebbard, John C; Logan, Anna S; Vanchipurakel, Golda A; Gilbert, Yamiece E

    2012-03-01

    Mu opioid receptors are densely expressed in the patch compartment of striatum and contribute to methamphetamine-induced patch-enhanced gene expression and stereotypy. To further elucidate the role of mu opioid receptor activation in these phenomena, we examined whether activation of mu opioid receptors would enhance methamphetamine-induced stereotypy and prodynorphin, c-fos, arc and zif/268 expression in the patch and/or matrix compartments of striatum, as well as the impact of mu opioid receptor activation on the relationship between patch-enhanced gene expression and stereotypy. Male Sprague-Dawley rats were intrastriatally infused with d-Ala(2)-N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO; 1 μg/μL), treated with methamphetamine (0.5 mg/kg) and killed at 45 min or 2 h later. DAMGO augmented methamphetamine-induced zif/268 mRNA expression in the patch and matrix compartments, while prodynorphin expression was increased in the dorsolateral patch compartment. DAMGO pre-treatment did not affect methamphetamine-induced arc and c-fos expression. DAMGO enhanced methamphetamine-induced stereotypy and resulted in greater patch versus matrix expression of prodynorphin in the dorsolateral striatum, leading to a negative correlation between the two. These findings indicate that mu opioid receptors contribute to methamphetamine-induced stereotypy, but can differentially influence the genomic responses to methamphetamine. These data also suggest that prodynorphin may offset the overstimulation of striatal neurons by methamphetamine.

  5. ACTIVATION OF MU OPIOID RECEPTORS IN THE STRIATUM DIFFERENTIALLY AUGMENTS METHAMPHETAMINE-INDUCED GENE EXPRESSION AND ENHANCES STEREOTYPIC BEHAVIOR

    PubMed Central

    Horner, Kristen A.; Hebbard, John C.; Logan, Anna S.; Vanchipurakel, Golda A.; Gilbert, Yamiece E.

    2013-01-01

    Mu opioid receptors are densely expressed in the patch compartment of striatum and contribute to methamphetamine-induced patch-enhanced gene expression and stereotypy. In order to further elucidate the role of mu opioid receptor activation in these phenomena, we examined whether activation of mu opioid receptors would enhance methamphetamine-induced stereotypy and prodynorphin, c-fos, arc and zif/268 expression in the patch and/or matrix compartments of striatum, as well as the impact of mu opioid receptor activation on the relationship between patch-enhanced gene expression and stereotypy. Male Sprague-Dawley rats were intrastriatally infused with D-Ala(2)-N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO; 1 μg/μl), treated with methamphetamine (0.5 mg/kg) and sacrificed at 45 minutes or 2 hours later. DAMGO augmented methamphetamine-induced zif/268 mRNA expression in the patch and matrix compartments, while prodynorphin expression was increased in the dorsolateral patch compartment. DAMGO pretreatment did not affect methamphetamine-induced arc and c-fos expression. DAMGO enhanced methamphetamine-induced stereotypy and resulted in greater patch versus matrix expression of prodynorphin in the dorsolateral striatum, leading to a negative correlation between the two. These findings indicate that mu opioid receptors contribute to methamphetamine-induced stereotypy, but can differentially influence the genomic responses to methamphetamine. These data also suggest that prodynorphin may offset the overstimulation of striatal neurons by methamphetamine. PMID:22150526

  6. Global patterns of methamphetamine use.

    PubMed

    Chomchai, Chulathida; Chomchai, Summon

    2015-07-01

    As the most popular psychostimulant in the world, methamphetamine use has reached epidemic proportions. Its enormous popularity has created subcultures of methamphetamine users all over the globe. The purpose of this review is to describe the geographic availability of different types of methamphetamine, the characteristics of each user population, and the psychosocial impact the two have on society. Methamphetamine has diversified immensely from the early days of its use. Different forms of methamphetamine - ICE, powder, and pills - have different pharmacokinetic characteristics that make them popular among certain types of users. New studies have shown that addiction to methamphetamine results in a very characteristic loss of inhibition that augments various risk-taking behaviors in its users. Also, recent seizure data suggest that its production and trafficking is spreading into new areas of the globe. From recreational use to addiction, methamphetamine use represents a serious risk to health and wellbeing of the community. Recognizing the pattern of abuse in specific populations is the key to assessing the risk, implementing prevention, and harm reduction measures, as well as making public policies.

  7. Alterations in adult behavioral responses to cocaine and dopamine transporters following juvenile exposure to methamphetamine.

    PubMed

    McFadden, Lisa; Yamamoto, Bryan K; Matuszewich, Leslie

    2011-01-20

    The present experiment assessed whether preadolescent exposure to methamphetamine would alter adult behavioral responses to cocaine and dopamine transporter immunoreactivity in the striatum of male and female rats. Juvenile rats were injected once daily with 0 or 2 mg/kg methamphetamine from postnatal days 21 to 35 and tested in adulthood. Male rats, but not female rats, exposed to methamphetamine showed an increase in responsiveness to cocaine in the open field and an increase in dopamine transporter immunoreactivity in the striatum. These findings suggest that early exposure to methamphetamine can lead to sex specific altered responses to psychostimulants in adulthood, which may contribute to later vulnerability to drug use. Copyright © 2010 Elsevier B.V. All rights reserved.

  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.

  9. Presence and Persistence of Psychotic Symptoms in Cocaine- versus Methamphetamine-Dependent Participants

    PubMed Central

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

    2012-01-01

    The primary objective of this study was to compare and contrast psychotic symptoms reported by cocaine and methamphetamine-dependent individuals. Participants included 27 cocaine-dependent and 25 methamphetamine-dependent males, as well as 15 cocaine-dependent and 18 methamphetamine-dependent females. After screening, participants were excluded if they met criteria for any Axis I diagnosis other than nicotine dependence, or methamphetamine or cocaine dependence (ie, participants had to use either methamphetamine or cocaine but were excluded if they met dependence criteria for both). The participants were administered the newly developed Psychotic Symptom Assessment Scale (PSAS), which assesses psychotic symptoms. A high proportion of both cocaine- and methamphetamine-dependent men and women reported delusions of paranoia and auditory hallucinations. However, during the abstinent and intoxicated conditions, methamphetamine-dependent men and women were more likely than cocaine-dependent men and women to report psychotic symptoms. Future studies will compare psychotic symptoms reported by non-dependent recreational stimulant users to stimulant-dependent individuals. PMID:18393050

  10. Trace evidence of trans-phenylpropene as a marker of smoked methamphetamine.

    PubMed

    Shakleya, Diaa M; Plumley, Anna E; Kraner, James C; Bell, Suzanne M; Callery, Patrick S

    2008-10-01

    This case study investigates trans-phenylpropene as a potential marker for smoked methamphetamine. The decedent, a 31-year-old male, was found with paraphernalia that indicated that he may have been smoking abused drugs prior to death. Methamphetamine and cocaine were detected in the residue remaining in the paraphernalia. Markers of thermal degradation of methamphetamine and cocaine were also detected in the paraphernalia. Gas chromatography-mass spectrometry (GC-MS) analysis detected trans-phenylpropene as a marker of smoked methamphetamine and anhydroecgonine methyl ester as a marker of smoked cocaine. Both trans-phenylpropene and anydroecgonine methyl ester were detected in the urine of the decedent, connecting the link between the paraphernalia for smoking and the ingestion of the pyrolysis products of methamphetamine and cocaine. Several other drugs of abuse were identified either in blood and urine or in hexane extracts of the paraphernalia, including phenylacetone, fentanyl, norfentanyl, amphetamine, ecgonine methyl ester, oxycodone, acetaminophen, chlorpheniramine, and caffeine. Using a pyrolysis GC-MS, the characteristic pyrolytic products of cocaine HCl, methamphetamine HCl, and combinations of the two were evaluated and the results showed that combining the drugs in a single run did not alter the pyrolysis pattern. The detection of trans-phenylpropene in both biological specimens and in paraphernalia is the first example of this analyte being applied as evidence of smoked methamphetamine.

  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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. [A preliminary study on outpatient relapse prevention program for methamphetamine dependent patients: Serigaya Methamphetamine Relapse Prevention Program (SMARPP)].

    PubMed

    Kobayashi, Ohji; Matsumoto, Toshihiko; Otsuki, Masaki; Endo, Keiko; Okudaira, Kenichi; Harai, Hiroaki; Wada, Kiyoshi

    2007-10-01

    Although methamphetamine use disorder has been prevalent in Japan for more than fifty years, there have been hardly any effective medical treatment modalities other than improving methamphetamine-induced psychosis through hospitalization and/or participation in self help groups and private rehabilitation centers. As such limited social resources for recovering methamphetamine dependents are insufficient to prevent patients from relapse, there are growing needs for developing effective outpatient treatment program based on a chronic care perspective. We have developed a relapse prevention program for Japanese methamphetamine abusers, modifying "Matrix" model and incorporating other treatment materials. Then a preliminary study on implementing the program was conducted in an outpatient setting at Kanagawa Psychiatric Center, Serigaya Hospital. Of sixty eight methamphetamine dependent patients who visited the hospital for the first time between September 2006 and February 2007, four agreed to participate in the study. The program was manual- and workbook-based, and we suggested participants to attend to the session three-times per week for two months. Also participants were asked randomly to turn in urine samples once a week. The participants consisted of a female and three males, with an average age of thirty. The length of abstinent period since the last use varied substantially, from five days to more than four years. Three had the experience of serving in prison for violating the Stimulant Drugs Control Law. The results of the present study were that all four completed the program, and presented with negative urine samples throughout the period. However, in terms of treatment retention, two out of the four dropped out of the outpatient treatment within a month after the program termination. These outcomes suggest that a relapse prevention program may successfully be provided for Japanese methamphetamine abusers in an outpatient setting, with a favorable, treatment

  13. 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.

  14. Pre-clinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

    DTIC Science & Technology

    2014-12-01

    12 hours after TBI significantly improved cognition and functional behavior in 2-3 month old male Wistar rats . These studies were intended to examine...the therapeutic effects of methamphetamine in female and aged male rats . We also repeated a MRI time course study with the intent of determining if...there was a dose response effect associated with methamphetamine induced white matter track remodeling. We have determined that female rats represent

  15. Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus.

    PubMed

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

    2012-09-15

    Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced dose- and time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression.

  16. 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

  17. Crystal methamphetamine use among female street-based sex workers: Moving beyond individual-focused interventions.

    PubMed

    Shannon, Kate; Strathdee, Steffanie; Shoveller, Jean; Zhang, Ruth; Montaner, Julio; Tyndall, Mark

    2011-01-01

    Given growing concern of the sexual risks associated with crystal methamphetamine use and the dearth of research characterizing the use of methamphetamine among street-based sex workers (FSWs), this study aimed to characterize the prevalence and individual, social, and structural contexts of crystal methamphetamine use among FSWs in a Canadian setting. Drawing on data from a prospective cohort, we constructed multivariate logistic models to examine independent correlates of crystal methamphetamine among FSWs over a two-year follow-up period using generalized estimating equations. Of a total of 255 street-based FSWs, 78 (32%) reported lifetime crystal methamphetamine use and 24% used crystal methamphetamine during the two-year follow-up period, with no significant associations between methamphetamine use and sexual risk patterns. In a final multivariate GEE model, FSWs who used crystal methamphetamine had a higher proportional odds of dual heroin injection (adjOR=2.98, 95%CI: 1.35-5.22), having a primary male sex partner who procures drugs for them (adjOR=1.79, 95%CI: 1.02-3.14), and working (adjOR=1.62, 95%CI: 1.04-2.65) and living (adjOR=1.41, 95%CI: 1.07-1.99) in marginalized public spaces. The findings highlight the crucial need to move beyond the individual to gender-focused safer environment interventions that mediate the physical and social risk environment of crystal methamphetamine use among FSWs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. CRYSTAL METHAMPHETAMINE USE AMONG FEMALE STREET-BASED SEX WORKERS: MOVING BEYOND INDIVIDUAL-FOCUSED INTERVENTIONS

    PubMed Central

    Shannon, K; Strathdee, SA; Shoveller, J; Zhang, R; Montaner, JS; Tyndall, MW

    2012-01-01

    Given growing concern of the sexual risks associated with crystal methamphetamine use and the dearth of research characterizing the use of methamphetamine among street-based sex workers (FSWs), this study aimed to characterize the prevalence and individual, social, and structural contexts of crystal methamphetamine use among FSWs in a Canadian setting. Drawing on data from a prospective cohort, we constructed multivariate logistic models to examine independent correlates of crystal methamphetamine among FSWs over a two-year follow-up period using generalized estimating equations. Of a total of 255 street-based FSWs, 78 (32%) reported lifetime crystal methamphetamine use and 24% used crystal methamphetamine during the two-year follow-up period, with no significant associations between methamphetamine use and sexual risk patterns. In a final multivariate GEE model, FSWs who used crystal methamphetamine had a higher proportional odds of dual heroin injection (adjOR = 2.98, 95%CI: 1.35–5.22), having a primary male sex partner who procures drugs for them (adjOR = 1.79, 95%CI: 1.02–3.14), and working (adjOR = 1.62, 95%CI: 1.04–2.65) and living (adjOR = 1.41, 95%CI: 1.07–1.99) in marginalized public spaces. The findings highlight the crucial need to move beyond the individual to gender-focused safer environment interventions that mediate the physical and social risk environment of crystal methamphetamine use among FSWs. PMID:20810223

  19. Methamphetamine self-administration in mice decreases GIRK channel-mediated currents in midbrain dopamine neurons.

    PubMed

    Sharpe, Amanda L; Varela, Erika; Bettinger, Lynne; Beckstead, Michael J

    2014-10-31

    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. 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. 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. Our results suggest that methamphetamine self-administration decreases GIRK channel-mediated currents in dopaminergic neurons and that this effect may be calcium dependent. © The Author 2015. Published by Oxford University Press on

  20. 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…

  1. Methamphetamine and ethanol interactions in humans.

    PubMed

    Mendelson, J; Jones, R T; Upton, R; Jacob, P

    1995-05-01

    Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg). Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA. Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine. Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine. As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.

  2. 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…

  3. 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. © 2015 Wiley Periodicals, Inc.

  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.

  5. A fatality from an oral ingestion of methamphetamine.

    PubMed

    Kiely, Elizabeth; Lee, C Jeff; Marinetti, Laureen

    2009-10-01

    The case presented is of a 49-year-old white male decedent who admitted to oral ingestion of methamphetamine. He believed he was being followed by the police while walking his daughter to school in the morning and swallowed the "8-ball of meth," which is known to be one-eighth of an ounce or the equivalent of about 3 g. The following autopsy specimens were analyzed for the presence of methamphetamine and amphetamine by gas chromatography-mass spectrometry: femoral blood, urine, bile, vitreous fluid, brain, liver, and gastric contents. Blood drawn at the hospital approximately 12 h after ingestion was also analyzed. The methamphetamine concentration in the hospital blood was 3.0 mg/L, and the concentration in the femoral blood from autopsy was 30 mg/L. Other drugs confirmed included tramadol, lorazepam, and 11-carboxy-Delta(9)-tetrahydrocannabinol. The pathologist ruled the cause of death to be cardiac dysrhythmia due to excited delirium as a result of methamphetamine drug effects. Discussion of the timeline from ingestion to death and the clinical presentation of the decedent are included.

  6. Methamphetamine-associated cardiomyopathy: patterns and predictors of recovery.

    PubMed

    Voskoboinik, A; Ihle, J F; Bloom, J E; Kaye, D M

    2016-06-01

    Methamphetamine abuse is a growing public health problem, and increasing numbers of patients are admitted with methamphetamine-associated cardiomyopathy (MAC). We sought to characterise the patterns of this disease and identify predictors of recovery. We retrospectively studied consecutive patients diagnosed with MAC between January 2006 and July 2015. We identified 20 patients (14 males, 6 females) with mean age 35 ± 9 years. Most had very severe systolic dysfunction (mean left ventricular ejection fraction (LVEF) 19.7 ± 11.4%) at presentation with 14 requiring inotropes and 5 requiring mechanical support. The pattern of systolic dysfunction was global in 14 patients, while 6 patients had a 'reverse Takotsubo' (RT) pattern with severely hypokinetic basal-mid segments and apical preservation. RT patients were predominantly female, had a short history of methamphetamine abuse and had higher cardiac enzyme levels. Patients with global dysfunction tended to have mid-wall fibrosis on cardiac magnetic resonance imaging. On follow-up transthoracic echocardiography, 6 out of 19 (32%) had normalisation of LVEF (LVEF ≥ 50%) within 6 weeks. Smaller left ventricular and left atrial size, shorter duration of methamphetamine use and RT pattern appeared to predict early recovery. A subset of MAC patients, particularly those with a RT pattern and lesser ventricular dilatation have the potential for early recovery of ventricular function. By contrast, those with evidence of myocardial fibrosis and ventricular enlargement have limited scope for recovery. © 2016 Royal Australasian College of Physicians.

  7. The effects of methamphetamine self-administration on behavioural sensitization in the olfactory bulbectomy rat model of depression.

    PubMed

    Kucerova, Jana; Pistovcakova, Jana; Vrskova, Dagmar; Dusek, Ladislav; Sulcova, Alexandra

    2012-11-01

    Depression is frequently comorbid with a drug addiction and may seriously complicate its treatment. Currently, there is no routinely used animal model to investigate this comorbidity. In this study the effect of repeated administration of methamphetamine on i.v. drug self-administration in an olfactory bulbectomy model of depression in rats was investigated in order to propose and validate a rat model of comorbid depression and addiction. Male Wistar rats were either olfactory-bulbectomized (OBX) or sham-operated. They subsequently underwent a methamphetamine sensitization regime, which consisted of daily i.p. injections of methamphetamine for a 14-d period; controls received Sal injections at the same frequency. The i.v. self-administration of methamphetamine (0.08 mg/kg in one infusion) paradigm on a fixed ratio schedule of reinforcement was performed using operant chambers. A significant decrease of the drug intake was recorded in sham-operated animals pretreated with methamphetamine when compared to the unpretreated group. This was not apparent in the OBX groups. Both groups of OBX animals exhibited a higher intake of methamphetamine compared to the corresponding sham-operated groups, thus confirming the hypothesis of higher drug intake in depressive conditions in this rodent model. The procedure of behavioural sensitization to methamphetamine decreased the number of self-administered drug doses per session in the sham-operated rats. It is hypothesized that this phenomenon resulted from increasing efficacy of the drug after behavioural sensitization caused by repeated methamphetamine intermittent administration.

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

    PubMed Central

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

    2013-01-01

    Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it acts in part as an agonist. SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative σ receptor antagonist with nanomolar affinity and selectivity for σ receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established σ receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate σ receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity. PMID:22921523

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

    PubMed

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

    2013-08-01

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

  10. 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.

  11. Methamphetamine: putting the brakes on speed.

    PubMed

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

    2006-04-01

    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 problem still persists. In fact, a 2004 survey indicates that an alarming 6.2% of high school seniors have tried methamphetamine. A number of biological, genetic, and environmental factors influence children's and adolescents' paths to substance abuse. Nurses should recognize the symptoms of methamphetamine abuse, which include agitation; aggressive behavior; rapid mood swings; hypertension; tachycardia; and eventually lesion-marked skin, clinical depression, and paranoid psychosis. Treatment for methamphetamine addiction includes behavioral therapy. Research on pharmacologic therapy is lacking. Educating youth on methamphetamine prevention appears to be the best approach to curb the spreading use of this addictive and deadly drug.

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

    PubMed

    Kobori, Eiko; Visrutaratna, Surasing; Maeda, Yuko; Wongchai, Siriporn; Kada, Akiko; Ono-Kihara, Masako; Hayami, Yoko; Kihara, Masahiro

    2009-05-15

    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. 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. 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). 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.

  13. Juvenile exposure to methamphetamine attenuates behavioral and neurochemical responses to methamphetamine in adult rats.

    PubMed

    McFadden, Lisa M; Carter, Samantha; Matuszewich, Leslie

    2012-04-01

    Previous research has shown that children living in clandestine methamphetamine (MA) labs are passively exposed to the drug [1]. The long-term effects of this early exposure on the dopaminergic systems are unknown, but may be important for adult behaviors mediated by dopamine, such as drug addiction. The current study sought to determine if juvenile exposure to low doses of MA would lead to altered responsiveness to the stimulant in adulthood. Young male and female rats (PD20-34) were injected daily with 0 or 2 mg/kg MA or left undisturbed and then tested at PD90. In the open field, adult rats exposed to MA during preadolescence had reduced locomotor activity compared to control non-exposed rats following an acute injection of MA (2 mg/kg). Likewise, methamphetamine-induced dopamine increases in the dorsal striatum were attenuated in male and female rats that had been exposed to MA as juveniles, although there were no changes in basal in vivo or ex vivo dopamine levels. These findings suggest that exposure of juveniles to MA leads to persistent changes in the behavioral and neurochemical responses to stimulants in adulthood.

  14. Comparison of systemic and local methamphetamine treatment on acetylcholine and dopamine levels in the ventral tegmental area in the mouse.

    PubMed

    Dobbs, L K; Mark, G P

    2008-10-15

    Acetylcholine (ACh) is an important mediator of dopamine (DA) release and the behavioral reinforcing characteristics of drugs of abuse in the mesocorticolimbic pathway. Within the ventral tegmental area (VTA), the interaction of DA with ACh appears to be integral in mediating motivated behaviors. However, the effects of methamphetamine on VTA ACh and DA release remain poorly characterized. The current investigation performed microdialysis to evaluate the effects of methamphetamine on extracellular levels of ACh and DA. Male C57BL/6J mice received an i.p. injection (saline, 2 mg/kg, or 5 mg/kg) and an intra-VTA infusion (vehicle, 100 microM or 1 mM) of methamphetamine. Locally perfused methamphetamine resulted in no change in extracellular ACh compared with vehicle, but caused a strong, immediate and dose-dependent increase in extrasynaptic DA levels (1240% and 2473% of baseline, respectively) during the 20-min pulse perfusion. An i.p. injection of methamphetamine increased extrasynaptic DA to 275% and 941% of baseline (2 mg/kg and 5 mg/kg, respectively). Systemic methamphetamine significantly increased ACh levels up to 275% of baseline for 40-60 min (2 mg/kg) and 397% of baseline for 40-160 min (5 mg/kg) after injection. ACh remained elevated above baseline for 2-3 h post injection, depending on the methamphetamine dose. Methamphetamine-induced locomotor activity was dose-dependently correlated with extrasynaptic VTA ACh, but not DA levels. These data suggest that methamphetamine acts in the VTA to induce a robust and short-lived increase in extracellular DA release but acts in an area upstream from the VTA to produce a prolonged increase in ACh release in the VTA. We conclude that methamphetamine may activate a recurrent loop in the mesocorticolimbic DA system to stimulate pontine cholinergic nuclei and produce a prolonged ACh release in the VTA.

  15. Comparison of Systemic and Local Methamphetamine Treatment on Acetylcholine and Dopamine Levels in the Ventral Tegmental Area in the Mouse

    PubMed Central

    Dobbs, Lauren K.; Mark, Gregory P.

    2008-01-01

    Acetylcholine (ACh) is an important mediator of dopamine (DA) release and the behavioral reinforcing characteristics of drugs of abuse in the mesocorticolimbic pathway. Within the ventral tegmental area (VTA), the interaction of DA with ACh appears to be integral in mediating motivated behaviors. However, the effects of methamphetamine on VTA ACh and DA release remain poorly characterized. The current investigation performed microdialysis to evaluate the effects of methamphetamine on extracellular levels of ACh and DA. Male C57BL/6J mice received an IP injection (saline, 2 mg/kg, or 5 mg/kg) and an intra-VTA infusion (vehicle, 100 µM or 1 mM) of methamphetamine. Locally perfused methamphetamine resulted in no change in extracellular ACh compared to vehicle, but caused a strong, immediate and dose-dependent increase in extrasynaptic DA levels (1240% and 2473% of baseline, respectively) during the 20-minute pulse perfusion. An IP injection of methamphetamine increased extrasynaptic DA to 275% and 941% of baseline (2 mg/kg and 5 mg/kg, respectively). Systemic methamphetamine significantly increased ACh levels up to 275% of baseline for 40 – 60 minutes (2 mg/kg) and 397% of baseline for 40 – 160 minutes (5 mg/kg) after injection. ACh remained elevated above baseline for 2 to 3 hours post injection, depending on the methamphetamine dose. Methamphetamine-induced locomotor activity was dose-dependently correlated with extrasynaptic VTA ACh, but not DA levels. These data suggest that methamphetamine acts in the VTA to induce a robust and short-lived increase in extracellular DA release but acts in an area upstream from the VTA to produce a prolonged increase in ACh release in the VTA. We conclude that methamphetamine may activate a recurrent loop in the mesocorticolimbic DA system to stimulate pontine cholinergic nuclei and produce a prolonged ACh release in the VTA. PMID:18760336

  16. 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

  17. Methamphetamine-associated psychosis.

    PubMed

    Grant, Kathleen M; LeVan, Tricia D; Wells, Sandra M; Li, Ming; Stoltenberg, Scott F; Gendelman, Howard E; Carlo, Gustavo; Bevins, Rick A

    2012-03-01

    Methamphetamine (METH) is a frequent drug of abuse in U.S. populations and commonly associated with psychosis. This may be a factor in frequent criminal justice referrals and lengthy treatment required by METH users. Persecutory delusions and auditory hallucinations are the most consistent symptoms of METH-associated psychosis (MAP). MAP has largely been studied in Asian populations and risk factors have varied across studies. Duration, frequency and amount of use as well as sexual abuse, family history, other substance use, and co-occurring personality and mood disorders are risk factors for MAP. MAP may be unique with its long duration of psychosis and recurrence without relapse to METH. Seven candidate genes have been identified that may be associated with MAP. Six of these genes are also associated with susceptibility, symptoms, or treatment of schizophrenia and most are linked to glutamatergic neurotransmission. Animal studies of pre-pulse inhibition, attenuation of social interaction, and stereotypy and alterations in locomotion are used to study MAP in rodents. Employing various models, rodent studies have identified neuroanatomical and neurochemical changes associated with METH use. Throughout this review, we identify key gaps in our understanding of MAP and suggest potential directions for future research.

  18. A role for mGluR5 receptors in intravenous methamphetamine self-administration.

    PubMed

    Osborne, Megan P H; Olive, M Foster

    2008-10-01

    Selective antagonists of the mGluR5 receptor attenuate rewarding and reinforcing effects of various drugs of abuse, including alcohol, nicotine, and cocaine. However, the ability of mGluR5 antagonists to alter the reinforcing effects of methamphetamine has not yet been explored. In this study, male Sprague-Dawley rats were trained to perform an operant lever-pressing task in order to obtain intravenous infusions of methamphetamine (0.2 mg/kg/infusion) or presentation of food pellets on a fixed ratio (FR1) schedule of reinforcement. After stabilization of methamphetamine or food self-administration, the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]pyridine (MTEP; 0.3, 1.0, or 3.0 mg/kg i.p.) or vehicle were administered to the animals in a randomized counterbalanced cross-over design. MTEP at doses of 1.0 and 3.0 mg/kg significantly reduced methamphetamine self-administration by 26 and 36%, respectively, but did not alter food reinforcement at any dose tested. These data suggest that mGluR5 receptors are involved in the reinforcing effects of methamphetamine, and that antagonists of this receptor may serve as novel pharmacologic agents for the treatment of addiction to methamphetamine.

  19. 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

  20. Discriminative-stimulus effects of second generation synthetic cathinones in methamphetamine-trained rats.

    PubMed

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

    2015-04-01

    Synthetic cathinones are beta-ketophenethylamine analogs manufactured to avoid legal restrictions placed on illicit stimulants like methamphetamine. Regulating these "emerging" designer drugs require scientific evidence of abuse potential. 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. 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. 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 potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans.

    PubMed

    Kirkpatrick, Matthew G; Gunderson, Erik W; Johanson, Chris-Ellyn; Levin, Frances R; Foltin, Richard W; Hart, Carl L

    2012-04-01

    There are no studies directly comparing self-administration of methamphetamine and d-amphetamine by humans. This study compared intranasal methamphetamine- and d-amphetamine self-administration and characterized the mood, performance and physiological effects produced by the drugs. A randomized, double-blind, placebo-controlled, cross-over study. An out-patient research unit at the New York State Psychiatric Institute. Male recreational methamphetamine users (n = 13). Five 2-day blocks of sessions were conducted. On the first day of each block, participants 'sampled' a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamine plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money). There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines increased self-administration dose-dependently, with 41% drug choices overall. Under the $20 condition, only 17% drug options were selected. Both drugs increased cardiovascular activity and 'positive' mood, although methamphetamine produced more prominent effects on some measures (e.g. heart rate and ratings of 'high'). Methamphetamine and d-amphetamines appear to produce a similar dose-related profile of effects in humans, which supports their equivalence for abuse potential. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  2. Methamphetamine and human immunodeficiency virus protein Tat synergize to destroy dopaminergic terminals in the rat striatum.

    PubMed

    Theodore, S; Cass, W A; Maragos, W F

    2006-02-01

    Dysfunction of the dopaminergic system accompanied by loss of dopamine in the striatum is a major feature of human immunodeficiency virus-1-associated dementia. Previous studies have shown that human immunodeficiency virus-1-associated dementia patients with a history of drug abuse have rapid neurological progression, prominent psychomotor slowing, more severe encephalitis and more severe dendritic and neuronal damage in the frontal cortex compared with human immunodeficiency virus-1-associated dementia patients without a history of drug abuse. In a previous study, we showed that methamphetamine and human immunodeficiency virus-1 protein Tat interact to produce a synergistic decline in dopamine levels in the rat striatum. The present study was carried out to understand the underlying cause for the loss of dopamine. Male Sprague-Dawley rats were administered saline, methamphetamine, Tat or Tat followed by methamphetamine 24 h later. Two and seven days later the animals were killed and tissue sections from striatum were processed for silver staining to examine terminal degeneration while sections from striatum and substantia nigra were processed for tyrosine hydroxylase immunoreactivity. Striatal tissue was also analyzed by Western blotting for tyrosine hydroxylase protein levels. Compared with controls, methamphetamine+Tat-treated animals showed extensive silver staining and loss of tyrosine hydroxylase immunoreactivity and protein levels in the ipsilateral striatum. There was no apparent loss of tyrosine hydroxylase in the substantia nigra. Markers for oxidative stress were significantly increased in striatal synaptosomes from Tat+methamphetamine group compared with controls. The results indicate that methamphetamine and Tat interact to produce an enhanced injury to dopaminergic nerve terminals in the striatum with sparing of the substantia nigra by a mechanism involving oxidative stress. These findings suggest a possible mode of interaction between methamphetamine

  3. 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

  4. Development of murine monoclonal antibodies to methamphetamine and methamphetamine analogues.

    PubMed

    Danger, Yannic; Gadjou, Caroline; Devys, Anne; Galons, Hervé; Blanchard, Dominique; Folléa, Gilles

    2006-02-20

    Methamphetamine and ecstasy are addictive drugs that cause major health problems in young people. Here we report on the development of high-affinity monoclonal antibodies to methamphetamine and its analogues, which may constitute powerful tools for antibody-based therapy. Six haptens, methamphetamine and ecstasy analogues, were synthesized, linked to a carrier protein and injected into mice. Several specific monoclonal antibodies were subsequently obtained following fusion of splenocytes from the immunized animals, with Sp2/O cells. Antibody specificity was fully investigated by competition ELISA, using a series of analogues, to identify specific amphetamine and/or ecstasy-specific antibodies. Antibody affinity was estimated to be in the range of 10(8) M(-1) with an enantiomeric hapten. Finally, two characteristic hybridoma clones (DAS-M243-6H5 and DAS-M278-4B12), secreting specific and potent mAbs were isolated. The development of drug-specific antibodies as in this study may provide promising therapeutic insight into how to neutralize methamphetamine in vivo during acute intoxication.

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

    PubMed

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

    2008-05-01

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

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

    PubMed Central

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

    2013-01-01

    Aims To describe temporal trends in methamphetamine use among young injection drug users (IDU) in San Francisco. Design and Methods Secondary analysis of cross-sectional baseline data collected for a longitudinal study of young IDU from 1998 to 2004. Participants were 1445 young IDU (< 30 years old) who reported injection in the previous month, English-speaking, and recruited by street outreach methods. We examined trends for: lifetime (ever) and recent (30-day) methamphetamine use, including injected and non-injected, and by age group and sexual risk behaviour [men who have sex with men injecting drug users (MSM-IDU), male IDU (non-MSM) and female IDU]. Results In 1998, 1999, 2000, 2001, 2003 and 2004 we interviewed 237, 276, 431, 310, 147 and 44 participants, respectively. Overall, median age was 22 years [interquartile range (IQR) 20 – 25], 30.3% were women and median duration of injecting was 4.4 years (IQR 2 – 7). Prevalence of methamphetamine use was high, with 50.1% reporting recent injection, but overall there were no temporal increases in reported ‘ever’ injected use. Recent methamphetamine injection (past 30 days) increased significantly, and peaked at 60% in 2003. MSM-IDU had higher methamphetamine injection ever (92.3%) and recently (59.5%) compared to heterosexual male (non-MSM) IDU (81.6% and 47.3%, respectively) and to female IDU (78.4% and 46.1%, respectively). Conclusions Despite reports of ubiquitous increases in methamphetamine use, there were no significant increases in 6 years in ever injecting methamphetamine overall among young IDU. MSM-IDU who reported the highest methamphetamine use overall reported some increases in recent injected use. The methamphetamine ‘epidemic’ was probably under way among young IDU earlier than other populations. PMID:18368610

  7. A Case of a Spontaneous Self-resolving Retrobulbar Hemorrhage Following 3,4-Methylenedioxy-methamphetamine Use.

    PubMed

    Chervenkoff, Jordan V; Rajak, Saul N; Selva, Dinesh; Davis, Garry

    2016-10-20

    This case report discusses the case of a 23-year-old male patient who experienced retrobulbar pain, diplopia, proptosis, and mild lower eyelid bruising after consuming 3,4-methylenedioxy-methamphetamine. The symptoms settled over 10 days and vision returned to normal without intervention. The authors discuss the differential diagnosis relevant to the presenting complaints and propose several mechanisms linking 3,4-methylenedioxy-methamphetamine use to spontaneous nontraumatic intraorbital hematoma.

  8. 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

  9. Gray-matter volume in methamphetamine dependence: cigarette smoking and changes with abstinence from methamphetamine.

    PubMed

    Morales, Angelica M; Lee, Buyean; Hellemann, Gerhard; O'Neill, Joseph; London, Edythe D

    2012-10-01

    Group differences in brain structure between methamphetamine-dependent and healthy research participants have been reported, but findings in the literature present discrepancies. Although most methamphetamine-abusing individuals also smoke cigarettes, the effects of smoking on brain structure have not been distinguished from those of methamphetamine. Changes with abstinence from methamphetamine have also been relatively unexplored. This study, therefore, attempted to account for effects of smoking and brief abstinence from methamphetamine on gray-matter measures in methamphetamine-dependent research participants. Gray matter was measured using voxel-based morphometry in three groups: 18 control nonsmokers, 25 control smokers, and 39 methamphetamine-dependent smokers (methamphetamine-abstinent 4-7 days). Subgroups of methamphetamine-dependent and control participants (n=12/group) were scanned twice to determine change in gray matter over the first month of methamphetamine abstinence. Compared with Control Nonsmokers, Control Smokers and Methamphetamine-dependent Smokers had smaller gray-matter volume in the orbitofrontal cortex and caudate nucleus. Methamphetamine-dependent Smokers also had smaller gray-matter volumes in frontal, parietal and temporal cortices than Control Nonsmokers or Smokers, and smaller gray-matter volume in insula than control nonsmokers. Longitudinal assessment revealed gray matter increases in cortical regions (inferior frontal, angular, and superior temporal gyri, precuneus, insula, occipital pole) in methamphetamine-dependent but not control participants; the cerebellum showed a decrease. Gray-matter volume deficits in the orbitofrontal cortex and caudate of methamphetamine-dependent individuals may be in part attributable to cigarette smoking or pre-morbid conditions. Increase in gray matter with methamphetamine abstinence suggests that some gray-matter deficits are partially attributable to methamphetamine abuse. Copyright © 2012

  10. Gray-Matter Volume in Methamphetamine Dependence: Cigarette Smoking and Changes with Abstinence from Methamphetamine*

    PubMed Central

    Morales, Angelica; Lee, Buyean; Hellemann, Gerhard; O’Neill, Joseph; London, Edythe D.

    2012-01-01

    Background Group differences in brain structure between methamphetamine-dependent and healthy research participants have been reported, but findings in the literature present discrepancies. Although most methamphetamine-abusing individuals also smoke cigarettes, the effects of smoking on brain structure have not been distinguished from those of methamphetamine. Changes with abstinence from methamphetamine have also been relatively unexplored. This study, therefore, attempted to account for effects of smoking and brief abstinence from methamphetamine on gray-matter measures in methamphetamine-dependent research participants. Methods Gray matter was measured using voxel-based morphometry in three groups: 18 Control Nonsmokers, 25 Control Smokers, and 39 Methamphetamine-dependent Smokers (methamphetamine-abstinent 4–7 days). Subgroups of methamphetamine-dependent and control participants (n = 12/group) were scanned twice to determine change in gray matter over the first month of methamphetamine abstinence. Results Compared with Control Nonsmokers, Control Smokers and Methamphetamine-dependent Smokers had smaller gray-matter volume in the orbitofrontal cortex and caudate nucleus. Methamphetamine-dependent smokers also had smaller gray-matter volumes in frontal, parietal and temporal cortices than Control Nonsmokers or Smokers, and smaller gray-matter volume in insula than Control Nonsmokers. Longitudinal assessment revealed gray matter increases in cortical regions (inferior frontal, angular, and superior temporal gyri, precuneus, insula, occipital pole) in methamphetamine-dependent but not control participants; the cerebellum showed a decrease. Conclusions Gray-matter volume deficits in the orbitofronal cortex and caudate of methamphetamine-dependent individuals may be in part attributable to cigarette smoking or pre-morbid conditions. Increase in gray matter with methamphetamine abstinence suggests that some gray-matter deficits are partially attributable to

  11. Illicit methamphetamine: analysis, synthesis, and availability.

    PubMed

    Puder, K S; Kagan, D V; Morgan, J P

    1988-01-01

    Methamphetamine has been marketed illicitly since the 1960s. Much of the street material was illicitly synthesized. Although methamphetamine quality was variable in the past decade, it has emerged since 1978 as the only street stimulant which is likely to contain what it purports to contain. Although there is a small volume of legitimate methamphetamine still made by the pharmaceutical industry, most material analyzed by street-drug laboratories appears to have been illegitimately synthesized and not diverted. For a decade, relatively little methamphetamine was submitted to street-drug analytical labs. In recent years, although the absolute volume of methamphetamine submissions changed little, this drug made up the bulk of alleged stimulant samples submitted to such facilities because of the paucity of amphetamine submissions. Methamphetamine synthesis and use appears to constitute a small but continuing portion of the illicit drug market.

  12. Crystal in Iran: methamphetamine or heroin kerack

    PubMed Central

    2013-01-01

    In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications. PMID:23497450

  13. “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

  14. Reinforcing effects of methamphetamine in planarians.

    PubMed

    Kusayama, T; Watanabe, S

    2000-08-03

    Reinforcing properties of dopamine agonist, methamphetamine, for planarians were examined with the conditioned place preference (CPP) procedure. The planarians showed preference for the environment associated with methamphetamine administration. This reinforcing effect was antagonized by pretreatment with non-selective dopamine antagonist, haloperidol. Both selective D1 antagonist SCH23390 and selective D2 antagonist sulpiride also blocked the reinforcing effect of methamphetamine. These results suggest that reinforcing effects of dopaminergic drugs can be traced back to invertebrates such as planarians.

  15. Variability and specificity associated with environmental methamphetamine sampling and analysis.

    PubMed

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

    2011-11-01

    This study was designed to explore the efficacy of the use of wipe sampling to determine methamphetamine contamination associated with the clandestine manufacture of methamphetamine. Three laboratories were utilized to analyze wipe samples to investigate variability in reported methamphetamine concentration among samples spiked with known amounts of methamphetamine. Different sampling media, surfaces, and solvents were also utilized to determine potential differences in measured methamphetamine concentration due to different wipes, wipe solvents, and wipe contaminants. This study examined rate of false positive detection among blank samples and whether interference with common household substances would create a false positive detection of methamphetamine. Variability between the three labs-using liquid chromatography with mass spectrometry or gas chromatography with mass spectrometry for detection of a known concentration of methamphetamine-resulted in percent differences of 3-30%. Results from wipe sample analysis for methamphetamine, using methanol or isopropanol, showed no significant difference in methamphetamine contamination recovery. Dust and paint contamination on methamphetamine wipe samples with known methamphetamine spike amounts did not affect methamphetamine wipe sample recovery. This study confirmed that either methanol or isopropanol is an appropriate solvent for use in methamphetamine wipe sampling. Dust and paint contamination on wipe samples will not interfere with the wipe sample analysis for methamphetamine. False positive detection for methamphetamine was not observed in any of the blank wipe samples submitted for the study. Finally, this study determined that methamphetamine will not be detected in structures that are truly methamphetamine free at current laboratory limits of quantification.

  16. Methamphetamine use: hazards and social influences.

    PubMed

    Wermuth, L

    2000-01-01

    Use of methamphetamine, a potent central nervous system stimulant, increased in the early- to mid-1990s in the United States, concentrated in the west, midwest, and south. The use and trade of methamphetamine was facilitated by a fairly simple production process and the involvement of numerous small entrepreneurs as well as drug-trafficking syndicates. National data from the 1994 Drug Abuse Warning network revealed that for the period from 1991 to 1994 methamphetamine use among short-stay hospital patients more than tripled, and methamphetamine-related deaths reported by medical examiner offices nearly tripled. In addition, the Treatment Episode Data Set revealed a 43 percent increase in treatment-program admissions in which clients identified methamphetamine as the primary drug of abuse. Nonetheless, methamphetamine use did not become widespread in the U.S. population. Low-income and unemployed young white men continue to be the group most likely to use methamphetamine, but by the mid-1990s the drug had increased in popularity in more diverse populations and regions. Economic and social pressures experienced by a broad array of Americans may partially explain expanded methamphetamine use; for example, depressed economic conditions in rural and semi-rural areas have contributed to methamphetamine's appeal as a source of income. A "war against drugs" approach has characterized the policy response, with increased criminal justice penalties. A public health approach is recommended, including prevention campaigns, harm-reduction outreach and treatment approaches, and pharmacologic and abstinence-based drug treatment approaches.

  17. Immunological consequences of methamphetamine protein glycation.

    PubMed

    Dickerson, Tobin J; Yamamoto, Noboru; Ruiz, Diana I; Janda, Kim D

    2004-09-22

    The drug of abuse methamphetamine has been found to participate in the aberrant glycation of proteins. The importance of this chemical process has been shown wherein mouse albumin was readily modified with methamphetamine, and injection of this protein into mice yields a significant immune response, even in the absence of adjuvants. Competition experiments revealed that although methamphetamine binds weakly to the elicited antibodies, the primary epitope is composed of both the methamphetamine moiety and glucose-derived cross-linking region. Implications of this phenonomenon in the context of drug addiction are discussed.

  18. Oral health of the methamphetamine abuser.

    PubMed

    Donaldson, Mark; Goodchild, Jason H

    2006-11-01

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

  19. 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

  20. [Histopathological study on acute poisoning of methamphetamine, morphine or cocaine].

    PubMed

    Maruta, T; Nihira, M; Tomita, Y

    1997-04-01

    Methamphetamine, morphine or cocaine was injected intraperitoneally into Wistar rats (male, 6 weeks old) at a dose of 50 mg/kg, 125 mg/kg, or 50 mg/kg body weight, respectively. These doses of drugs were determined to ensure that the rats would show signs of drug intoxication and survive for a day. Over the period from 5 min to 18 hr after injection, concentrations of the drugs and metabolites in blood were analyzed by the GC/MS method, and the histopathological changes of the heart, lungs, liver and kidneys were examined by light microscopy. The time of maximum drug concentration in the blood after injection was 5 min in the methamphetamine-treated group, 1 hr (total morphine) in the morphine group and 5 min in the cocaine group. These blood concentrations decreased with time. In the liver at 2.5 hr after injection of methamphetamine, centrolobular vacuolation and diffuse eosinophilic changes of hepatocytes appeared. At 6 hr this damage spread to the midzone of the liver and partial necrosis of the centrolobe was found. At 18 hr the liver damage became worse and necrosis was also found in the midzone of the liver. In the heart, from 2.5 hr, eosinophilic changes of the myocardium were observed diffusely. Furthermore, at 18 hr, partial inflammatory cell infiltration and contraction bands were observed. The degree of histopathological damage did not coincide with the time of maximum drug concentration. In the morphine group, centrolobular and midzonal vacuolation, diffuse fatty degeneration and eosinophilic changes were observed in the liver from 2.5 hr to 18 hr after the administration. No necrosis was found, perhaps because the rats did not suffer the hyperthermia observed in the methamphetamine group. The degree of histopathological damage became more serious with time, as it did in the methamphetamine group. In the cocaine group, no histopathological changes were observed, probably because the doses of cocaine were too small to cause histopathological damage, and

  1. Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats.

    PubMed

    Carson, Dean S; Cornish, Jennifer L; Guastella, Adam J; Hunt, Glenn E; McGregor, Iain S

    2010-01-01

    There is emerging evidence that the neuropeptide oxytocin may be utilised as a treatment for various psychopathologies, including drug addictions. Here we used an animal model to assess whether oxytocin might be effective in the treatment of methamphetamine addiction. Sprague-Dawley rats were trained to lever press to intravenously self-administer methamphetamine under a progressive ratio schedule of reinforcement. Once responding had stabilised, one group of rats received escalating doses of oxytocin (0.001, 0.01, 0.1, 0.3, 1 mg/kg) administered intraperitoneally (IP) prior to daily self-administration tests, while other rats received vehicle. After these tests, lever-pressing was extinguished and the ability of methamphetamine primes (IP, 1 mg/kg) to reinstate responding was studied with and without co-administration of oxytocin (IP, 0.3 and 1 mg/kg). Results showed that oxytocin dose-dependently reduced responding for intravenous methamphetamine with an almost complete absence of responding at the highest oxytocin dose (1 mg/kg). Hyperactivity during methamphetamine self-administration was also dose-dependently reduced by oxytocin. Oxytocin (1 but not 0.3 mg/kg) also reduced the ability of methamphetamine to reinstate methamphetamine-seeking behaviour. In separate tests, oxytocin (IP, 0.3 and 1 mg/kg) robustly decreased the hyperactivity and rearing induced by methamphetamine challenge (IP, 1 mg/kg), producing activity levels similar to control animals. This study suggests that oxytocin may have a powerful inhibitory effect on the motivation to consume methamphetamine and on hyperactivity associated with acute methamphetamine intoxication. These results point to the potential utility of human trials of oxytocin as a therapeutic treatment for methamphetamine addiction.

  2. Methamphetamine use, aggressive behavior and other mental health issues among high-school students in Cape Town, South Africa.

    PubMed

    Plüddemann, Andreas; Flisher, Alan J; McKetin, Rebecca; Parry, Charles; Lombard, Carl

    2010-06-01

    Methamphetamine use has become a growing problem in a number of countries over the past two decades, but has only recently emerged in South Africa. This study investigated the prevalence of methamphetamine use among high-school students in Cape Town and whether students reporting methamphetamine use were more likely to be at risk for mental health and aggressive behavior problems. A cross-sectional survey of 15 randomly selected high schools in Cape Town, of 1561 males and females grade 8-10 students (mean age 14.9), was conducted using the Problem Oriented Screening Instrument for Teenagers (POSIT) and the Beck Depression Inventory (BDI). Findings indicated that 9% of the students had tried methamphetamine at least once. Ordinal logistic regression analyses showed that methamphetamine use in the past year was significantly associated with higher aggressive behavior scores (OR=1.81, 95% CI: 1.04-3.15, p<0.05), mental health risk scores (OR=2.04, 95% CI: 1.26-3.31, p<0.01) and depression scores (OR=2.65, 95% CI: 1.64-4.28, p<0.001). Methamphetamine use has become a serious problem in Cape Town, particularly among adolescents. Screening adolescents in school settings for methamphetamine use and behavior problems may be useful in identifying youth at risk for substance misuse, providing an opportunity for early intervention. These findings have implications for other parts of the world where methamphetamine use may be occurring at younger ages and highlight the importance of looking at co-morbid issues related to methamphetamine use. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Methamphetamine use, aggressive behavior and other mental health issues among high school students in Cape Town, South Africa

    PubMed Central

    Plüddemann, Andreas; Flisher, Alan J.; McKetin, Rebecca; Parry, Charles; Lombard, Carl

    2010-01-01

    Objective Methamphetamine use has become a growing problem in a number of countries over the past two decades, but has only recently emerged in South Africa. This study investigated the prevalence of methamphetamine use among high-school students in Cape Town and whether students reporting methamphetamine use were more likely to be at risk for mental health and aggressive behavior problems. Method A cross-sectional survey of 15 randomly selected high-schools in Cape Town, of 1561 male and female grade 8–10 students (mean age 14.9), was conducted using the Problem Oriented Screening Instrument for Teenagers (POSIT) and the Beck Depression Inventory (BDI). Results Findings indicated that 9% of the students had tried methamphetamine at least once. Ordinal logistic regression analyses showed that methamphetamine use in the past year was significantly associated with higher aggressive behavior scores (OR = 1.81, 95% CI: 1.04–3.15, p < 0.05), mental health risk scores (OR = 2.04, 95% CI: 1.26–3.31, p < 0.01) and depression scores (OR = 2.65, 95% CI: 1.64–4.28, p < 0.001). Conclusions Methamphetamine use has become a serious problem in Cape Town, particularly among adolescents. Screening adolescents in school settings for methamphetamine use and behavior problems may be useful in identifying youth at risk for substance misuse, providing an opportunity for early intervention. These findings have implications for other parts of the world where methamphetamine use may be occurring at younger ages and highlight the importance of looking at co-morbid issues related to methamphetamine use. PMID:20064699

  4. Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment.

    PubMed

    Numachi, Yohtaro; Yoshida, Sumiko; Yamashita, Motoyasu; Fujiyama, Ko; Toda, Shigenobu; Matsuoka, Hiroo; Kajii, Yasushi; Nishikawa, Toru

    2007-09-07

    Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in synaptic connectivity. EphA5 receptors constitute large families of tyrosine kinase receptor and are expressed almost exclusively in the nervous system, especially in the limbic structures. Recent studies suggest EphA5 to be important in the topographic projection, development, and plasticity of limbic structures, and to be involved in dopaminergic neurotransmission. We used in situ hybridization to examine whether methamphetamine alters EphA5 mRNA expression in the brains of adult male Wister rats. EphA5 mRNA was widely distributed in the medial frontal cortex, cingulate cortex, piriform cortex, hippocampus, habenular nucleus and amygdala. Compared to baseline expression at 0h, EphA5 mRNA was significantly decreased (by 20%) in the medial frontal cortex at 24h, significantly increased (by 30%) in the amygdala at 9 and 24h, significantly but transiently decreased (by 30%) in the habenular nucleus at 1h after a single injection of methamphetamine. Methamphetamine did not change EphA5 mRNA expression in the cingulate cortex, piriform cortex or hippocampus. Our results that methamphetamine altered EphA5 mRNA expression in rat brain suggest methamphetamine could affect patterns of synaptic connectivity, which might be responsible for methamphetamine-induced chronic brain dysfunctions.

  5. 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:…

  6. 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:…

  7. 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.

  8. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  9. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Methamphetamine test system. 862.3610 Section 862....3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine...

  10. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Methamphetamine test system. 862.3610 Section 862....3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine...

  11. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methamphetamine test system. 862.3610 Section 862....3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine...

  12. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methamphetamine test system. 862.3610 Section 862....3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine...

  13. Methamphetamine abuse and "meth mouth".

    PubMed

    Rhodus, Nelson L; Little, James W

    2005-01-01

    Dental management for the patient who abuses drugs is always a challenge. The number of patients abusing methamphetamines appears to be increasing. The dentist needs to be aware of the clinical presentation and medical risks presented by these patients and to attempt to get the patient to seek professional help. Additionally, special attention will be necessary for the high prevalence and severity of oral manifestations including rampant caries, enamel erosion, xerostomia, bruxism, and muscle trismus.

  14. 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 ...

  15. Methamphetamine abuse and "meth mouth".

    PubMed

    Rhodus, Nelson L; Little, James W

    2008-01-01

    Dental management for the patient who abuses drugs is always a challenge. The numbers of patients abusing methamphetamines appears to be increasing. The dentist needs to be aware of the clinical presentation and medical risks presented by these patients and to attempt to get the patient to seek professional help. Additionally, special attention will be necessary for the high prevalence and severity or oral manifestations including: rampant caries, enamel erosion, xerostomia, bruxism and muscle trismus.

  16. Methamphetamine exposures in young children.

    PubMed

    Matteucci, Michael J; Auten, Jonathan D; Crowley, Brian; Combs, Daniel; Clark, Richard F

    2007-09-01

    Methamphetamine abuse is reaching epidemic proportions. As this occurs, the likelihood of accidental poisoning in children increases. We sought to evaluate the presentation, treatment, and outcome of pediatric methamphetamine exposures reported to the California Poison Control System. This is a retrospective review of California Poison Control System records for methamphetamine exposure from 2000 through 2004. All charts of patients identified as younger than 6 years were reviewed and abstracted. The charts of 47 children younger than 6 years were identified and reviewed. Three were coded as minor effects, 3 as major effects, and 16 as moderate effects. The remainder of the charts were not evaluated because of no effect (n = 6), unrelated or confirmed nonexposure (n = 3), or unable to follow (n = 16). The most common presenting symptom was agitation (82%), whereas seizures were documented in only 2 cases (9%). Tachycardia was common (mean heart rate, 171 beats/min; confidence interval [CI], 154-187), whereas blood pressure (BP) (mean systolic BP, 120 mm Hg; CI, 104-136; and mean diastolic BP, 70 mm Hg; CI, 51-88) and rectal temperature (mean, 37.4 degrees C; CI, 36.9-37.9) were slightly elevated compared with normal values. Creatinine was documented in 6 cases and noted as normal in all (0.3IU/L; CI, 0.2-0.4), whereas creatine kinase was documented in 3 charts and elevated in all (mean 1984 IU/L; range, 212-4942 IU/L). Most cases (55%) received benzodiazepines as treatment, although only 2 received activated charcoal. Symptoms persisted for an average of 22 hours (CI, 16.3-27.2). No deaths were reported. In this series of children, methamphetamine exposure was strongly associated with agitation that was successfully treated with benzodiazepines. Tachycardia was common, although hypertension and hyperthermia were not. Laboratory studies were not routinely recorded. The clinical significance of elevated creatine kinase concentrations recorded in 3 children is unclear.

  17. Intimate partner violence among men and women who use methamphetamine: A mixed-methods study in South Africa.

    PubMed

    Watt, Melissa H; Guidera, Kathryn E; Hobkirk, Andréa L; Skinner, Donald; Meade, Christina S

    2017-01-01

    The prevalence of methamphetamine use has risen dramatically in parts of South Africa. Globally, methamphetamine has been linked to intimate partner violence (IPV) and other forms of aggression. The aim of this mixed-methods study was to examine the experiences of physical IPV and its contextual factors among methamphetamine users in an urban community in Cape Town, South Africa. Active methamphetamine users were recruited using respondent driven sampling. All participants (n = 360) completed structured surveys, and a subset (n = 30) completed in-depth interviews with discussions of personal IPV experiences. Quantitative data were examined separately by gender, and regression models were used to identify factors that were associated with physical IPV victimisation and perpetration. Qualitative data were analysed to provide contextual understanding. In the past 3 months, 47% of women and 31% of men reported being a victim of IPV, and 30% of women and 28% men reported being a perpetrator of IPV. Victimisation and perpetration were highly correlated, and both were significantly associated with histories of other traumas. Although the survey data suggests gender equivalence in IPV, the qualitative data provides a more nuanced context, with female victimisation by male partners being particularly frequent and intense. In narratives, IPV was a product of male aggression while using methamphetamine, norms around sex trading and gender-based attitudes endorsing violence against women. Addiction to methamphetamine creates heightened risks of IPV, especially among those with previous traumas. The findings emphasise the importance of identifying and addressing IPV among methamphetamine users in South Africa. [Watt MH, Guidera KE, Hobkirk AL, Skinner D, Meade CS. Intimate partner violence among men and women who use methamphetamine: A mixed-methods study in South Africa. Drug Alcohol Rev 2017;36:97-106]. © 2016 Australasian Professional Society on Alcohol and other

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

    PubMed

    Brecht, Mary-Lynn; Herbeck, Diane

    2013-10-01

    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.

  19. 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

  20. 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…

  1. Methamphetamine-associated shock with intestinal infarction.

    PubMed

    Brannan, Temple A; Soundararajan, Suganthi; Houghton, Bruce L

    2004-12-29

    Methamphetamine abuse has increased rapidly in the United States over the last few years. Besides socioeconomic hardships acquired from using the drug, there are several adverse medical outcomes. Although there have been many reports of cardiovascular and central nervous system toxicities, there are few case reports of bowel ischemia induced by the drug. We report an unusual case of methamphetamine-associated intestinal infarction.

  2. 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…

  3. 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…

  4. 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…

  5. alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: pharmacological evaluation and interaction with methamphetamine.

    PubMed

    Moore, K A; Lichtman, A H; Poklis, A; Borzelleca, J F

    1995-08-01

    Methamphetamine is a popular drug of abuse, readily synthesized in clandestine laboratories. Illicitly obtained methamphetamine is frequently impure, containing various purposefully added diluents and adulterants, as well as impurities of manufacture and origin. Few impurities have been studied in vivo and limited information exists concerning their pharmacology/toxicology. One such impurity of manufacture is alpha-benzyl-N-methylphenethylamine (BNMPA). Acute toxicity and spontaneous activity (locomotor) studies were conducted with this compound alone and in combination with S(+)-methamphetamine (METH) in male, ICR mice. In the acute toxicity studies, BNMPA was evaluated for convulsant activity. While BNMPA also produced some behavioral disturbances similar to those seen with methamphetamine (e.g., stereotopy) at doses greater than 30 mg/kg, no tonic-clonic convulsions were noted until pre-terminal convulsion at 50 mg/kg. METH alone produced tonic-clonic convulsions at terminal doses of 70 mg/kg. When BNMPA was given in combination with METH, there was no readily apparent change in the convulsion profile from that of METH given alone. In spontaneous activity studies, doses of BNMPA ranging from 1 mg/kg to 50mg/kg failed to alter locomotor activity significantly from controls though 5 mg/kg METH alone significantly increased spontaneous activity. In addition, increases in spontaneous activity elicited by 5 mg/kg METH were not affected when METH was given with 5 mg/kg BNMPA. While BNMPA appears to have toxic effects in the central nervous system (CNS), the failure to affect locomotor activity or alter either METH-induced increases in spontaneous activity or METH-induced convulsions suggests that the two agents are producing their effects through distinct mechanisms.

  6. Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.

    PubMed

    Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Williams, Timothy; Ting, Hua; Lee, Shin-Da

    2014-06-01

    Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.

  7. Persistent behavioral and neurochemical sensitization to an acute injection of methamphetamine following unpredictable stress.

    PubMed

    Matuszewich, Leslie; Carter, Samantha; Anderson, Eden M; Friedman, Ross D; McFadden, Lisa M

    2014-10-01

    Prior research in humans and animals suggest that exposure to chronic stress alters the response to drugs of abuse, increasing vulnerability to drug addiction. Chronic unpredictable stress (CUS) has been shown to augment the increase of dopamine in the striatum when challenged with high doses of methamphetamine immediately following stress exposure, however it is not known whether this neurochemical stress-sensitization continues after the cessation of the stressors or if behavioral sensitization is also present. Therefore, the current study examined the immediate and delayed effects of CUS on methamphetamine-induced behaviors and striatal dopamine levels. Male rats were exposed to 10 days of CUS and then tested in either an open field box to assess locomotion or underwent in vivo microdialysis to measure striatal dopamine levels immediately following CUS or after a 1-2 week delay. All rats exposed to CUS showed a potentiated locomotor response immediately following an acute injection of 7.5mg/kg methamphetamine compared to non-stressed control rats. Both groups of CUS rats also showed augmented dopamine release and rectal temperatures following methamphetamine with prolonged increases in the CUS rats tested after a delay. These results suggest that CUS increases the sensitivity of a rat to a single injection of methamphetamine and that the increased sensitivity persists for up to 2 weeks following the last stressor.

  8. Infant death associated with maternal methamphetamine use during pregnancy and delivery: A case report.

    PubMed

    Sakai, Kentaro; Iwadate, Kimiharu; Maebashi, Kyoko; Matsumoto, Sari; Takasu, Shojiro

    2015-09-01

    The case described in this report is of a male infant who was found dead in a closet. His mother delivered the infant in the kitchen, left him wrapped in a towel, and called emergency medical services 4days after the delivery. At the autopsy, the growth suggests a full-term delivery, significant pathological findings were not observed, and the infant was estimated to be stillborn. After the autopsy, the police investigation discovered that the mother used a stimulant during the pregnancy and shortly before the rupture of the membrane. Toxicological analysis showed 1.60mg/L of methamphetamine in the blood, strongly suggesting that the fetal death was associated with this acute intoxication. Thus far, only a few cases of infant deaths have been reported in association with methamphetamine intoxication. The present case showed the highest blood concentration of methamphetamine compared to the past infant cases with this intoxication.

  9. Management of methamphetamine abuse and dependence.

    PubMed

    Ling, Walter; Rawson, Richard; Shoptaw, Steve; Ling, Walter

    2006-10-01

    Preliminary implications for evidence-based treatments and future practice may be drawn from new research findings that inspire a fresh view of methamphetamine dependence and associated medical consequences. Current user populations include increasingly impacted subgroups (ie, youths, women, men who have sex with men, and rural residents); complex consequences of methamphetamine abuse among these subgroups require additional efforts involving contextual understanding of characteristics and needs to develop effective treatments. The neurobiological data on cellular activity of methamphetamine taken with findings from neuroimaging studies indicate potential targets for pharmacologic interventions. In early trials, several candidate medications--bupropion, modafinil, and, to a lesser extent, baclofen--have shown promise in treating aspects of methamphetamine dependence, including aiding memory function necessary to more effectively participate in and benefit from behavioral therapies. Clinicians and researchers must interact to efficiently address the problems of methamphetamine dependence, a major drug problem in the United States and the world.

  10. Evaluation of the 20% D-methamphetamine requirement for determining illicit use of methamphetamine in urine.

    PubMed

    Esposito, Francis M; Crumpton, Susan; Mitchell, John; Flegel, Ronald R

    2012-07-01

    In urine drug testing, enantiomer analysis is used to determine whether a positive methamphetamine result could be due to use of an over-the-counter (OTC) nasal inhaler containing L-methamphetamine. D-methamphetamine at more than 20% of the total is considered indicative of a source other than an OTC product. This interpretation is based on a 1991 Department of Health and Human Services (HHS) Technical Advisory. We performed studies to verify the methamphetamine enantiomer content of current OTC nasal inhalers and to evaluate current laboratory testing capabilities. This study demonstrated that OTC inhalers contain less than 1% D-methamphetamine. A proficiency testing (PT) set for HHS-certified laboratories performing methamphetamine enantiomer testing found D-methamphetamine percentages that were consistently 1 to 3% higher than theoretical due to optical impurity of the derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (L-TPC). The PT results also demonstrate that laboratories can accurately determine 20% D-methamphetamine in samples with total methamphetamine concentrations down to 250 ng/mL. Based on these studies, the guideline of >20% D-methamphetamine is appropriate for interpreting results obtained using current laboratory methods.

  11. Modeling human methamphetamine use patterns in mice: chronic and binge methamphetamine exposure, reward function and neurochemistry.

    PubMed

    Kesby, James P; Chang, Ariel; Markou, Athina; Semenova, Svetlana

    2017-02-21

    Different methamphetamine use patterns in human subjects may contribute to inconsistent findings regarding the effects of methamphetamine abuse on brain and behavior. The present study investigated whether human-derived chronic and binge methamphetamine use patterns have differential effects on reward and neurochemistry in mice. Brain reward function in mice was evaluated during acute/prolonged withdrawal, and in response to methamphetamine challenge using the intracranial self-stimulation procedure. Brain dopaminergic, serotonergic and glutamatergic neurochemistry was determined with high-performance liquid chromatography. Chronic and binge regimens induced withdrawal-related decreases in reward function that were more severe during the binge regimen during cycles 1-2. Despite large differences in methamphetamine dose, both regimens induced similar reward deficits during cycles 3-4. Neither methamphetamine regimen led to persistent alterations in the sensitivity to the reward-enhancing effects of acute methamphetamine challenge. The binge regimen severely depleted striatal dopamine levels and increased brain glutamine levels. The chronic regimen had milder effects on striatal dopamine levels and altered cortical dopamine and serotonin levels. This work highlights that the magnitude of acute/prolonged withdrawal may not reflect amount or frequency of methamphetamine intake. In contrast, the array of underlying neurochemical alterations was methamphetamine regimen dependent. Thus, stratifying methamphetamine-dependent individuals based on use pattern may help to cater therapeutic interventions more appropriately by targeting use pattern-specific neurotransmitter systems.

  12. Association between GSTM1 and GSTT1 polymorphisms and susceptibility to methamphetamine dependence

    PubMed Central

    Khalighinasab, Mohammad Rashid; Saify, Khyber; Saadat, Mostafa

    2015-01-01

    Glutathione S-transferases (GSTs; EC: 2.5.1.18) are ubiquitous multifunctional enzymes, which play a key role in cellular detoxification. Functional genetic polymorphisms in genes encoding GSTM1 (a member of GST class mu; OMIM: 138350), and GSTT1 (a member of GST class theta; OMIM: 600436) have been well defined. The functional null alleles of GSTM1 and GSTT1 represent deletions of GSTM1 and GSTT1 genes, respectively. The aim of the present study is to investigate the association between GSTM1 and GSTT1 polymorphisms and methamphetamine dependence. The present population-based case-control study was performed in Shiraz (southern Iran). In total, 52 methamphetamine dependence (11 females, 41 males) and 635 healthy controls (110 females, 525 males) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Neither GSTM1 (OR=0.92, 95% CI: 0.52-1.61, P=0.771) nor GSTT1 (OR=0.71, 95% CI: 0.33-1.54, P=0.381) null genotypes were significantly associated with risk of methamphetamine dependence. It should be noted that although there was no association between the GSTM1 null genotype and risk of methamphetamine dependence, in both genders, there was significant interaction between gender and GSTM1 polymorphism (P=0.029). The combination genotypes of the GSTM1 and GSTT1 polymorphisms revealed that the genotypes of these two polymorphisms had no additive effect in relation to the susceptibility to methamphetamine dependence. The present study revealed that genetic polymorphisms of GSTT1 and GSTM1 are not risk factors for methamphetamine dependence. PMID:27843993

  13. Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats.

    PubMed

    Pritchard, Laurel M; Hensleigh, Emily; Lynch, Sarah

    2012-09-01

    Neonatal maternal separation (MS) has been used to model the effects of early life stress in rodents. MS alters behavioral responses to a variety of abused drugs, but few studies have examined its effects on methamphetamine sensitivity. We sought to determine the effects of MS on locomotor and stereotyped responses to low-to-moderate doses of methamphetamine in male and female adolescent rats. Male and female rat pups were subjected to 3 h per day of MS on postnatal days (PN) 2-14 or a brief handling control procedure during the same period. During adolescence (approximately PN 40), all rats were tested for locomotor activity and stereotyped behavior in response to acute methamphetamine administration (0, 1.0, or 3.0 mg/kg, s.c.). MS rats of both sexes exhibited increased locomotor activity in a novel environment, relative to handled controls. MS increased the locomotor response to methamphetamine (METH), and this effect occurred at different doses for male (3.0 mg/kg) and female (1.0 mg/kg) rats. MS also increased stereotyped behavior in response to METH (1.0 mg/kg) in both sexes. MS enhances the locomotor response to METH in a dose- and sex-dependent manner. These results suggest that individuals with a history of early life stress may be particularly vulnerable to the psychostimulant effects of METH, even at relatively low doses.

  14. Deprenyl treatment attenuates long-term pre- and post-synaptic changes evoked by chronic methamphetamine.

    PubMed

    Davidson, Colin; Chen, Qiang; Zhang, Xiuwn; Xiong, Xueying; Lazarus, Cindy; Lee, Tong H; Ellinwood, Everett H

    2007-11-14

    Deprenyl, used clinically in Parkinson's disease, has multiple pharmacological effects which make it a good candidate to treat neurotoxicity. Thus, we investigated deprenyl's ability to attenuate methamphetamine-induced dopamine neurotoxicity. We also examined deprenyl's effect in changing markers associated with psychostimulant sensitization. A potential therapeutic effect on either pathological domain would be a boon in developing novel treatments for methamphetamine abuse. Adult male Sprague-Dawley rats were split into 6 groups. Three groups received a 7-day saline minipump with saline, 0.05 or 0.25 mg/kg SC deprenyl injections given for 10 days before, during and 5 days after the 7-day saline minipump implant. Similarly, 3 groups received methamphetamine pumps (25 mg/kg/day) with escalating daily injections of methamphetamine (0-6 mg/kg) in addition to the minipump treatment. These rats also received saline, 0.05 or 0.25 mg/kg deprenyl injections given before, during and the 7-day minipump treatment. Rats were killed on day 28 of withdrawal and brain samples taken. HPLC analysis for dopamine and 3,4-Dihydroxy-Phenylacetic Acid (DOPAC) revealed a loss of dopamine in the caudate and accumbens which was partially reversed by high dose deprenyl. Tyrosine hydroxylase immunostaining in the midbrain was unaffected by methamphetamine, suggesting that dopamine neurotoxicity was localized to the caudate. Western blot analysis of the caudate after methamphetamine revealed little change in Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid (AMPA) GluR1 or N-Methyl-d-Aspartate (NMDA) NR2B subunits, or their phosphorylation state. However, methamphetamine increased levels of GluR1 and its phosphorylation state in the prefrontal cortex (PFC), and these increases were attenuated by deprenyl. Methamphetamine also increased levels of PFC NR2B subunit, but these increases were not attenuated by deprenyl. We suggest that deprenyl may be effective in reducing the neurotoxic

  15. The effect of methamphetamine on an animal model of erectile function

    PubMed Central

    Tar, Moses T.; Martinez, Luis R.; Nosanchuk, Joshua D.; Davies, Kelvin P.

    2014-01-01

    In the U.S. methamphetamine is considered a first-line treatment for attention-deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase-5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague-Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine (2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)) i.p. daily for three weeks and erectile function compared to untreated controls. The effect of co-administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals the ICP/BP ratio following 4 and 6mA stimulation decreased by approximately 50% compared to untreated animals and erectile dysfunction was also reversed by tadalafil. Overall our data suggests that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for

  16. Synthesis and pharmacological characterization of a novel sigma receptor ligand with improved metabolic stability and antagonistic effects against methamphetamine.

    PubMed

    Seminerio, Michael J; Robson, Matthew J; Abdelazeem, Ahmed H; Mesangeau, Christophe; Jamalapuram, Seshulatha; Avery, Bonnie A; McCurdy, Christopher R; Matsumoto, Rae R

    2012-03-01

    Methamphetamine interacts with sigma receptors at physiologically relevant concentrations suggesting a potential site for pharmacologic intervention. In the present study, a previous sigma receptor ligand, CM156, was optimized for metabolic stability, and the lead analog was evaluated against the behavioral effects of methamphetamine. Radioligand binding studies demonstrated that the lead analog, AZ66, displayed high nanomolar affinity for both sigma-1 and sigma-2 receptors (2.4 ± 0.63 and 0.51 ± 0.15, respectively). In addition, AZ66 had preferential affinity for sigma receptors compared to seven other sites and a significantly longer half-life than its predecessor, CM156, in vitro and in vivo. Pretreatment of male, Swiss Webster mice with intraperitoneal (10-20 mg/kg) or oral (20-30 mg/kg) dosing of AZ66 significantly attenuated the acute locomotor stimulatory effects of methamphetamine. Additionally, AZ66 (10-20 mg/kg, i.p.) significantly reduced the expression and development of behavioral sensitization induced by repeated methamphetamine administration. Taken together, these data indicate that sigma receptors can be targeted to mitigate the acute and subchronic behavioral effects of methamphetamine and AZ66 represents a viable lead compound in the development of novel therapeutics against methamphetamine-induced behaviors.

  17. Local pretreatment with the cannabinoid CB1 receptor antagonist AM251 attenuates methamphetamine intra-accumbens self-administration.

    PubMed

    Rodriguez, Jesse S; Boctor, Sherin Y; Flores, Luke C; Phelix, Clyde F; Martinez, Joe L

    2011-02-11

    The endocannabinoid system is a potential target for therapeutic intervention of substance abuse. Cannabinoid CB1 receptor antagonist decreases intravenous methamphetamine self-administration in animal models. This study examined whether the nucleus accumbens (NAcc) is a site of interaction between methamphetamine and the CB1 receptor antagonist AM251. Male Sprague-Dawley rats were trained to lever press and then were surgically implanted with a guide cannula into the right NAcc. Rats were allowed one week to recover and then AM251 (0.1 or 1.0 μg/μL) was reverse dialyzed directly into the NAcc prior to methamphetamine (10 μg/μL) intra-accumbens self-administration. AM251 (1.0 μg/μL) reduced methamphetamine self-administration while AM251 (0.1 μg/μL) had an intermediary effect. The mechanism of self-administration attenuation is not known but could be mediated by AM251 affecting the negative feedback from the NAcc to the ventral tegmental area (VTA). This study provides evidence that the endocannabinoid system is involved with rewarding effects of methamphetamine and suggests a possible therapeutic intervention for methamphetamine abuse. © 2010 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2010-07-10

    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-hour 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 2 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-hour 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.

  19. 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

  20. A Comparison of Echocardiographic Findings in Young Adults With Cardiomyopathy: With and Without a History of Methamphetamine Abuse

    PubMed Central

    Ito, Hiroki; Yeo, Khung-Keong; Wijetunga, Mevan; Seto, Todd B.; Tay, Kevin; Schatz, Irwin J.

    2013-01-01

    Background Methamphetamine is currently the most widespread illegal stimulant abused in the United States. No previous reports comparing echocardiographic findings of cardiomyopathy with and without a history of methamphetamine abuse are available. Methods We performed a single institution retrospective review of medical records and analyses of echocardiographic findings in patients ≤45 years of age hospitalized between 2001 and 2004 who were discharged with a diagnosis of cardiomyopathy or heart failure. After exclusion of patients with coronary artery disease or severe cardiac valvular disease, the remaining patients were divided into 2 groups based on their abuse or non abuse of methamphetamine, as determined by the documented history in the medical records or urine toxicology testing. Results Among a total of 59 patients, 28 (47%) had a history of methamphetamine abuse or positive urine toxicology. Both methamphetamine abusers and non-abusers were predominately male (64.3% vs 64.5%, P = .99), and had a high prevalence of obesity (55.6% vs 73.3%, P = .16). Bivariate analysis revealed significant differences between the methamphetamine abusers and non-abusers in left atrium volume (119.7 ± 55.4 ml vs 85.8 ± 33.5 ml, P = .008), left ventricular end-diastolic volume (201.9 ± 71.4 ml vs 156.6 ± 63.1 ml, P = .01), left ventricular end-systolic volume (136.0 ± 53.7 ml vs 92.3 ± 55.8 ml, P = .004), right ventricular dimension (26.3 ± 6.0 mm vs 21.3 ± 6.0 mm, P = .007), and quantified left ventricular ejection fraction (32.9% ± 11.3% vs 44.6% ± 17.8%, P = .004). Conclusions We found a high prevalence of methamphetamine abuse in our study population. Methamphetamine abusers had echocardiographic findings of more severe dilated cardiomyopathy compared with non-abusers. PMID:19330818

  1. A comparison of echocardiographic findings in young adults with cardiomyopathy: with and without a history of methamphetamine abuse.

    PubMed

    Ito, Hiroki; Yeo, Khung-Keong; Wijetunga, Mevan; Seto, Todd B; Tay, Kevin; Schatz, Irwin J

    2009-06-01

    Methamphetamine is currently the most widespread illegal stimulant abused in the United States. No previous reports comparing echocardiographic findings of cardiomyopathy with and without a history of methamphetamine abuse are available. We performed a single institution retrospective review of medical records and analyses of echocardiographic findings in patients < or = 45 years of age hospitalized between 2001 and 2004 who were discharged with a diagnosis of cardiomyopathy or heart failure. After exclusion of patients with coronary artery disease or severe cardiac valvular disease, the remaining patients were divided into 2 groups based on their abuse or non abuse of methamphetamine, as determined by the documented history in the medical records or urine toxicology testing. Among a total of 59 patients, 28 (47%) had a history of methamphetamine abuse or positive urine toxicology. Both methamphetamine abusers and non-abusers were predominately male (64.3% vs 64.5%, P = .99), and had a high prevalence of obesity (55.6% vs 73.3%, P = .16). Bivariate analysis revealed significant differences between the methamphetamine abusers and non-abusers in left atrium volume (119.7 +/- 55.4 ml vs 85.8 +/- 33.5 ml, P = .008), left ventricular end-diastolic volume (201.9 +/- 71.4 ml vs 156.6 +/- 63.1 ml, P = .01), left ventricular end-systolic volume (136.0 +/- 53.7 ml vs 92.3 +/- 55.8 ml, P = .004), right ventricular dimension (26.3 +/- 6.0 mm vs 21.3 +/- 6.0 mm, P = .007), and quantified left ventricular ejection fraction (32.9% +/- 11.3% vs 44.6% +/- 17.8%, P = .004). We found a high prevalence of methamphetamine abuse in our study population. Methamphetamine abusers had echocardiographic findings of more severe dilated cardiomyopathy compared with non-abusers. 2009 Wiley Periodicals, Inc.

  2. Methamphetamine self-administration produces attentional set-shifting deficits and alters prefrontal cortical neurophysiology in rats.

    PubMed

    Parsegian, Aram; Glen, W Bailey; Lavin, Antonieta; See, Ronald E

    2011-02-01

    Chronic methamphetamine abusers exhibit deficits in tasks requiring intact prefrontal cortex function, and prefrontal cortex dysfunction has been implicated in the loss of control over drug use. This study used a combination of behavioral and electrophysiologic assessments in rats with a history of long access methamphetamine self-administration to determine methamphetamine-induced changes in prefrontal cortex-dependent attentional set-shifting performance, drug-seeking, and prefrontal cortex neuronal activity. Male Long-Evans rats self-administered methamphetamine (.02 mg/infusion, intravenous) or received yoked saline infusions for 6 hours a day for 14 days. Cognitive flexibility was assessed using an attentional set-shifting task before 2 weeks of self-administration and 1 day after self-administration. Animals then underwent 11 days of abstinence, followed by three subsequent tests for context-induced drug seeking. Finally, animals were anesthetized, and single-unit in vivo extracellular recordings were performed in the dorsomedial prefrontal cortex. Methamphetamine-experienced rats showed escalated drug intake and context-induced drug-seeking following abstinence. During the extradimensional set-shift component, meth-experienced rats showed selective impairments that were identical to deficits produced by excitotoxic lesions of the prefrontal cortex. Rats with a history of chronic methamphetamine intake also exhibited higher basal firing frequency and a significantly greater proportion of burst-firing cells in the prefrontal cortex compared with yoked-saline controls. Prefrontal cortex-specific alterations in neuronal function may play a key role in methamphetamine-induced attentional deficits and drug-seeking. These data support the possibility that targeting prefrontal cortex pathology may improve treatment outcome in methamphetamine addiction. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Effects of methamphetamine abuse beyond individual users.

    PubMed

    Watanabe-Galloway, Shinobu; Ryan, Steve; Hansen, Katherine; Hullsiek, Brad; Muli, Victoria; Malone, A Cate

    2009-09-01

    Since 1997, the use of methamphetamine as a drug of abuse has been widespread in the United States. While several forms of amphetamine are useful in some areas of medicine, methamphetamine as an abused substance is associated with severe and multifaceted consequences. Problems associated with the abuse of amphetamine and its derivatives such as methamphetamine have been well documented. As the manufacture and use of methamphetamine across the United States has increased, the impact of methamphetamine abuse has been felt beyond individual users; families as well as communities can be seriously affected. An increase in child neglect and violence as well as a lack of resources for health care, social services, and law enforcement because of methamphetamine abuse have been reported by many communities. This study examines the historical spread of methamphetamine misuse in the United States and the resulting individual, social, and environmental consequences. A public health perspective on family, community, and social aspects is offered, and ideas for future research and policy changes are explored.

  4. Maxillary sinus manifestations of methamphetamine abuse

    PubMed Central

    Faucett, Erynne A.; Marsh, Katherine M.; Farshad, Kayven; Erman, Audrey B.

    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

  5. 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

  6. Residual methamphetamine in decontaminated clandestine drug laboratories.

    PubMed

    Patrick, Glen; Daniell, William; Treser, Charles

    2009-03-01

    This pilot cross-sectional study examined three previously decontaminated residential clandestine drug laboratories (CDLs) in Washington State to determine the distribution and magnitude of residual methamphetamine concentrations relative to the state decontamination standard. A total of 159 discrete random methamphetamine wipe samples were collected from the three CDLs, focusing on the master bedroom, bathroom, living room, and kitchen at each site. Additional samples were collected from specific non-random locations likely to be contacted by future residents (e.g., door knobs and light switches). Samples were analyzed for methamphetamine by EPA method 8270 for semivolatile organic chemicals. Overall, 59% of random samples and 75% of contact point samples contained methamphetamine in excess of the state decontamination standard (0.1 micro g/100 cm(2)). At each site, methamphetamine concentrations were generally higher and more variable in rooms where methamphetamine was prepared and used. Even compared with the less stringent standard adopted in Colorado (0.5 micro g/100cm(2)), a substantial number of samples at each site still demonstrated excessive residual methamphetamine (random samples, 25%; contact samples, 44%). Independent oversight of CDL decontamination in residential structures is warranted to protect public health. Further research on the efficacy of CDL decontamination procedures and subsequent verification of methods is needed.

  7. Glial dysfunction in abstinent methamphetamine abusers.

    PubMed

    Sailasuta, Napapon; Abulseoud, Osama; Harris, Kent C; Ross, Brian D

    2010-05-01

    Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized (13)C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1-(13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11 micromol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous (13)C MRS methods may determine 'cause and effect' between glial failure and neuronal injury.

  8. Impaired cognitive performance in subjects with methamphetamine dependence during exposure to neutral versus methamphetamine-related cues.

    PubMed

    Tolliver, Bryan K; Price, Kimber L; Baker, Nathaniel L; LaRowe, Steven D; Simpson, Annie N; McRae-Clark, Aimee L; Saladin, Michael E; DeSantis, Stacia M; Chapman, Elizabeth; Garrett, Margaret; Brady, Kathleen T

    2012-05-01

    Chronic methamphetamine abuse is associated with cognitive deficits that may impede treatment in methamphetamine-dependent patients. Exposure to methamphetamine-related cues can elicit intense craving in chronic users of the drug, but the effects of exposure to drug cues on cognitive performance in these individuals are unknown. This study assessed whether exposure to methamphetamine-related visual cues can elicit craving and/or alter dual task cognitive performance in 30 methamphetamine-dependent subjects and 30 control subjects in the laboratory. Reaction time, response errors, and inhibition errors were assessed on an auditory Go-No Go task performed by adult participants (total N = 60) while watching neutral versus methamphetamine-related video cues. Craving was assessed with the Within-Session Rating Scale modified for methamphetamine-dependent subjects. Exposure to methamphetamine-related cues elicited craving only in methamphetamine-dependent subjects. Even in the absence of methamphetamine cues, methamphetamine-dependent subjects exhibited slower reaction times and higher rates of both inhibition and response errors than control subjects did. Upon exposure to methamphetamine cues, rates of both response errors and inhibition errors increased significantly in methamphetamine-dependent subjects. Control subjects exhibited no increase in inhibition errors and only slightly increased rates of response errors upon exposure to methamphetamine cues. Response error rates, but not inhibition error rates or reaction times, during methamphetamine cue exposure were significantly associated with craving scores in methamphetamine-dependent subjects. Methamphetamine-dependent individuals exhibit cognitive performance deficits that are more pronounced during exposure to methamphetamine-related cues. Interventions that reduce cue reactivity may have utility in the treatment of methamphetamine dependence.

  9. Methamphetamine initiation among HIV-positive gay and bisexual men.

    PubMed

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

    2009-09-01

    This study describes factors associated with methamphetamine initiation in a racially diverse sample of 340 methamphetamine-using, HIV-positive gay and bisexual men. A factor analysis was conducted on reasons for initiation, and four factors were identified: to party, to cope, for energy, and to improve self-esteem. Methamphetamine to party accounted for more than one-third of the variance in the factor analysis. Methamphetamine to cope captured almost 9% of the variance, methamphetamine for energy accounted for approximately 8% of the variance, and methamphetamine for self-esteem accounted for approximately 7% of the variance. Regression analyses revealed differential associations between methamphetamine-initiation factors and HIV-risk behaviors. Methamphetamine for self-esteem predicted binge methamphetamine use, while methamphetamine to cope was associated with injecting methamphetamine. Using methamphetamine for energy was associated with number of illicit drugs-used and using methamphetamine to party was associated with having a greater number of sexually transmitted infections. These findings suggest that methamphetamine initiation among gay and bisexual men is multifaceted, which could have implications for intervention development.

  10. Are methamphetamine precursor control laws effective tools to fight the methamphetamine epidemic?

    PubMed

    Nonnemaker, James; Engelen, Mark; Shive, Daniel

    2011-05-01

    One of the most notable trends in illegal substance use among Americans over the past decade is the dramatic growth and spread of methamphetamine use. In response to the dramatic rise in methamphetamine use and its associated burden, a broad range of legislations has been passed to combat the problem. In this paper, we assess the impact of retail-level laws intended to restrict chemicals used to manufacture methamphetamine (methamphetamine precursor laws) in reducing indicators of domestic production, methamphetamine availability, and the consequences of methamphetamine use. Specifically, we examine trends in these indicators of methamphetamine supply and use over a period spanning the implementation of the federal Methamphetamine Anti-Proliferation Act (MAPA) (October 2000) and a more stringent state-level restriction enacted in California (January 2000). The results are mixed in terms of the effectiveness of legislative efforts to control methamphetamine production and use, depending on the strength of the legislation (California Uniform Controlled Substances Act versus federal MAPA), the specification of the comparison group, and the particular outcome of interest. Some evidence suggests that domestic production was impacted by these legislative efforts, but there is also evidence that prices fell, purities rose, and treatment episodes increased.

  11. Methamphetamine enhances sexual behavior in female rats.

    PubMed

    Winland, Carissa; Haycox, Charles; Bolton, Jessica L; Jampana, Sumith; Oakley, Benjamin J; Ford, Brittany; Ornelas, Laura; Burbey, Alexandra; Marquette, Amber; Frohardt, Russell J; Guarraci, Fay A

    2011-06-01

    The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual

  12. 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

  13. Methamphetamine abuse and emergency department utilization.

    PubMed Central

    Richards, J R; Bretz, S W; Johnson, E B; Turnipseed, S D; Brofeldt, B T; Derlet, R W

    1999-01-01

    Methamphetamine (MAP) abuse continues to increase worldwide, based on morbidity, mortality, drug treatment, and epidemiologic studies and surveys. MAP abuse has become a significant health care, environmental, and law enforcement problem. Acute intoxication often results in agitation, violence, and death. Chronic use may lead to infection, heart failure, malnutrition, and permanent psychiatric illness. MAP users frequently use the emergency department (ED) for their medical care. Over a 6-month period we studied the demographics, type, and frequency of medical and traumatic problems in 461 MAP patients presenting to our ED, which serves an area noted for high levels of MAP production and consumption. Comparison was made to the general ED population to assess use patterns. MAP patients were most commonly Caucasian males who lacked health insurance. Compared to other ED patients during this time, MAP patients used ambulance transport more and were more likely to be admitted to the hospital. There was a significant association between trauma and MAP use in this patient population. Our data suggest MAP users utilize prehospital and hospital resources at levels higher than the average ED population. Based on current trends, we can expect more ED visits by MAP users in the future. PMID:10344172

  14. Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2011-01-01

    Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance, and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed this 20-day within-participant, residential laboratory study. During four 5-day blocks of sessions, participants were administered oral methamphetamine (0, 10 mg) combined with alcohol (0, 0.375, 0.75 g/kg) three times (day 2: AM, day 2: PM, and day 3: PM). Breath alcohol concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and repeatedly thereafter. Subjective and objective sleep measures were also assessed; residual effects were assessed on days 3–5 of each block. Following the first drug administration, the methamphetamine–alcohol combination produced greater elevations of heart rate and ratings of “good drug effect” compared to either drug alone. Methamphetamine attenuated alcohol-related performance decrements and feelings of intoxication, whereas alcohol attenuated methamphetamine-related sleep disruptions. By the third administration, many of these effects were significantly diminished, suggesting that participants developed tolerance. Few residual effects were observed. These data show that methamphetamine combined with alcohol produced a profile of effects that was different from the effects of either drug alone. The largely positive effects of the drug combination (i.e., greater euphoria, and fewer performance and sleep disruptions) might explain why these drugs are often used in combination. PMID:21748253

  15. Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Johanson, Chris-Ellyn; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2012-01-01

    Aims Anecdotally, methamphetamine is considered to have a greater abuse potential compared to d-amphetamine, but there are no studies directly comparing self-administration of these drugs. This study characterized and compared self-administration as well as the mood, performance, and physiological effects of intranasal methamphetamine- and d-amphetamine. Design A randomized, double-blind, placebo-controlled, cross-over study. Setting An outpatient research unit at the New York State Psychiatric Institute. Participants Male recreational methamphetamine users (n = 13). Measurements Five 2-day blocks of sessions were conducted. On the first day of each block, participants “sampled” a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamines plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money). Findings There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines dose-dependently increased self-administration, whereas under the $20 condition, few drug options were selected. Overall, participants selected more drug choices under the $5 condition compared with the $20 condition (41% versus 17%). Both drugs increased cardiovascular activity and “positive” mood, although methamphetamine produced more prominent effects on some measures (e.g., heart rate and ratings of ‘high’). Conclusions These data are consistent with previous findings suggesting that the two amphetamines produce a similar dose-related profile of acute effects in humans, with methamphetamine producing greater effects on some mood and cardiovascular measures. The amphetamines were self-administered equally indicating their equivalence for abuse potential. PMID:22050030

  16. Live to tell: Narratives of methamphetamine-using women taken hostage by their intimate partners in San Diego, CA

    PubMed Central

    Ludwig-Barron, Natasha; Syvertsen, Jennifer L.; Lagare, Tiffany; Palinkas, Lawrence; Stockman, Jamila K.

    2015-01-01

    Background Hostage-taking, an overlooked phenomenon in public health, constitutes a severe form of intimate partner violence and may be a precursor to female homicide within relationships characterized by substance use. Criminal justice studies indicate that most hostage incidents are male-driven events with more than half of all cases associated with a prior history of violence and substance use. Methamphetamine use increases a woman’s risk of partner violence, with methamphetamine-using individuals being up to nine times more likely to commit homicide. As homicide is the most lethal outcome of partner violence and methamphetamine use, this study aims to characterize the potential role of hostage-taking within these intersecting epidemics. Methods Methamphetamine-using women enrolled in an HIV behavioural intervention trial (FASTLANE-II) who reported experiences of partner violence were purposively selected to participate in qualitative sub-studies (Women’s Study I & II). Twenty-nine women, ages 26–57, participated in semi-structured interviews that discussed relationship dynamics, partner violence, drug use and sexual practices. Results Findings indicated four cases of women being held hostage by a partner, with two women describing two separate hostage experiences. Women discussed partner jealousy, drug withdrawal symptoms, heightened emotional states from methamphetamine use, and escalating violent incidents as factors leading up to hostage-taking. Factors influencing lack of reporting incidents to law enforcement included having a criminal record, fear of partner retaliation, and intentions to terminate the relationship while the partner is incarcerated. Conclusion Educating women on the warning signs of hostage-taking within the context of methamphetamine use and promoting behaviour change among male perpetrators can contribute to reducing the risk of homicide. Furthermore, bridging the gap between health services and law enforcement agencies and

  17. Live to tell: Narratives of methamphetamine-using women taken hostage by their intimate partners in San Diego, CA.

    PubMed

    Ludwig-Barron, Natasha; Syvertsen, Jennifer L; Lagare, Tiffany; Palinkas, Lawrence A; Stockman, Jamila K

    2015-09-01

    Hostage-taking, an overlooked phenomenon in public health, constitutes a severe form of intimate partner violence and may be a precursor to female homicide within relationships characterized by substance use. Criminal justice studies indicate that most hostage incidents are male-driven events with more than half of all cases associated with a prior history of violence and substance use. Methamphetamine use increases a woman's risk of partner violence, with methamphetamine-using individuals being up to nine times more likely to commit homicide. As homicide is the most lethal outcome of partner violence and methamphetamine use, this study aims to characterize the potential role of hostage-taking within these intersecting epidemics. Methamphetamine-using women enrolled in an HIV behavioural intervention trial (FASTLANE-II) who reported experiences of partner violence were purposively selected to participate in qualitative sub-studies (Women's Study I & II). Twenty-nine women, ages 26-57, participated in semi-structured interviews that discussed relationship dynamics, partner violence, drug use and sexual practices. Findings indicated four cases of women being held hostage by a partner, with two women describing two separate hostage experiences. Women discussed partner jealousy, drug withdrawal symptoms, heightened emotional states from methamphetamine use, and escalating violent incidents as factors leading up to hostage-taking. Factors influencing lack of reporting incidents to law enforcement included having a criminal record, fear of partner retaliation, and intentions to terminate the relationship when the partner is incarcerated. Educating women on the warning signs of hostage-taking within the context of methamphetamine use and promoting behaviour change among male perpetrators can contribute to reducing the risk of homicide. Furthermore, bridging the gap between health services and law enforcement agencies and providing comprehensive services that address the

  18. Effects of methamphetamine on duration discrimination.

    PubMed

    Cevik, Münire Ozlem

    2003-08-01

    Experiments 1 and 2 address the controversy regarding the reliability of methamphetamine effects on interval timing. A temporal discrimination procedure was used, in which the rats were reinforced for pressing the left or the right levers after short and long signals, respectively. Methamphetamine (0.5 mg/kg sc) severely disrupted operant performance at 20-100 min after injection, which disabled the measurement of drug effects on temporal perception (Experiment 1). The same dose of methamphetamine shifted the psychometric function to the left at 100-180 min after injection, indicating an increase in subjective durations (Experiment 2). Although these results confirm the role of dopamine in interval timing, that a change in the speed of a neural clock mediates the methamphetamine-induced change in temporal perception is still a working hypothesis.

  19. Methamphetamine abuse and "meth mouth" in Europe.

    PubMed

    De-Carolis, Carlo; Boyd, Geraldine-A; Mancinelli, Luca; Pagano, Stefano; Eramo, Stefano

    2015-03-01

    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.

  20. Methamphetamine body stuffers: an observational case series.

    PubMed

    West, Patrick L; McKeown, Nathanael J; Hendrickson, Robert G

    2010-02-01

    We describe the demographics, characteristics, treatment, and clinical course of methamphetamine body stuffers. We also determine the clinical characteristics of methamphetamine body stuffers who have severe outcomes. A 6.5-year descriptive nonconcurrent observational case series evaluated methamphetamine body stuffers about whom the Oregon Poison Center was consulted by their primary physicians. Poison center charts were supplemented by completed hospital charts (for 95% of patients). Six hundred forty-eight patients with methamphetamine exposure were identified and reviewed, and 55 charts met the criteria for "methamphetamine body stuffer." We found the following characteristics of methamphetamine body stuffers: mean age 29 years (range 16 to 57 years), men in 44 of 55 cases (80%), mean time to arrival 2.7 hours after ingestion, with a median of 1 hour after ingestion. Ninety-seven percent (53/55) stuffed methamphetamine orally (2/55 rectally). Methamphetamine was most frequently swallowed in baggies, but 25% were unpackaged. The median dose ingested was 3.5 g of methamphetamine in 1 package. Outcome-based analysis revealed 29% (16/55) of patients had severe outcomes, as defined by end-organ toxicity, with agitation requiring intubation the most common severe outcome. There was 1 death reported. Toxicity did not appear to be related to the amount of methamphetamine or number of packets. Patients with severe outcomes had higher mean initial pulse rates and temperatures. Eighty-eight percent (14/16) of patients with severe outcomes had a presenting pulse rate greater than 120 beats/min or a temperature greater than 38 degrees C versus 18% (7/39) patients with a benign outcome. Twenty-four radiographic studies were obtained; none detected packets. Methamphetamine body stuffers have similar demographics to those of body stuffers of other stimulants, but tended to ingest fewer baggies with larger masses, and had a higher percentage of severe outcomes (29%) than

  1. Family dysfunction differentially affects alcohol and methamphetamine dependence: a view from the Addiction Severity Index in Japan.

    PubMed

    Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka

    2011-10-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

  2. Acute methamphetamine exposure inhibits cardiac contractile function.

    PubMed

    Turdi, Subat; Schamber, Robbie M; Roe, Nathan D; Chew, Herbert G; Culver, Bruce; Ren, Jun

    2009-09-10

    Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (+/-dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (+/-dLdt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), resting and electrically stimulated increase of intracellular Ca(2+) as well as intracellular Ca(2+) decay. Our results revealed that acute methamphetamine exposure depressed +/-dP/dt, PS and rise of intracellular Ca(2+) without affecting +/-dLdt, TPS, TR(90), resting intracellular Ca(2+) and intracellular Ca(2+) decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, +/-dLdt and shortened TR(90) without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban, associated with upregulated Na(+)-Ca(2+) exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response.

  3. Acute Methamphetamine Exposure Inhibits Cardiac Contractile Function

    PubMed Central

    Turdi, Subat; Schamber, Robbie M.; Roe, Nathan D.; Chew, Herbert G.; Culver, Bruce; Ren, Jun

    2009-01-01

    Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30 min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam® system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (± dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (± dLdt), time-to-PS (TPS), time-to-90% relengthening (TR90), resting and electrically-stimulated increase of intracellular Ca2+ as well as intracellular Ca2+ decay. Our results revealed that acute methamphetamine exposure depressed ± dP/dt, PS and rise of intracellular Ca2+ without affecting ± dLdt, TPS, TR90, resting intracellular Ca2+ and intracellular Ca2+ decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, ± dLdt and shortened TR90 without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban, associated with upregulated Na+-Ca2+ exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response. PMID:19481142

  4. Epidemiology of methamphetamine abuse in Missouri.

    PubMed

    Topolski, James M

    2007-01-01

    Methamphetamine use has spread over the past decade from the West to other regions of the nation. Since 2000, Missouri has ranked first in clandestine laboratory incidents. The continuing threat of Mexican-produced methamphetamine tempers recent reduction of clandestine laboratory incidents in Missouri. There are a number of consequences related to the use of the drug and Missouri's healthcare professionals could potentially play key roles in prevention and treatment of the problem.

  5. 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

  6. The neurobiology of methamphetamine induced psychosis.

    PubMed

    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.

  7. What You Need to Know about Drugs: Methamphetamines

    MedlinePlus

    ... use. Long-term use of methamphetamines can cause brain damage that causes problems with memory and body movement, mood swings, and violent behavior. When used in larger doses, methamphetamines can cause ...

  8. Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment.

    PubMed

    DeYoung, Dustin Z; Heinzerling, Keith G; Swanson, Aimee-Noelle; Tsuang, John; Furst, Benjamin A; Yi, Yi; Wu, Ying Nian; Moody, David E; Andrenyak, David M; Shoptaw, Steven J

    2016-08-01

    Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events. Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence.

  9. The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia.

    PubMed

    Sulaiman, Ahmad Hatim; Said, Mas Ayu; Habil, Mohd Hussain; Rashid, Rusdi; Siddiq, Amer; Guan, Ng Chong; Midin, Marhani; Nik Jaafar, Nik Ruzyanei; Sidi, Hatta; Das, Srijit

    2014-01-01

    The objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. This was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. Of 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612-19.708), bipolar disorder (OR=13.807, 95 CI=5.194-36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702-23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154-7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375-7.914) were the only factors associated with current psychosis. There was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

    Darke, Shane; Duflou, Johan; Kaye, Sharlene

    2017-10-01

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

  11. Systemic affects of methamphetamine use.

    PubMed

    Hauer, Patrick

    2010-08-01

    Methamphetamine (meth) is the most widely used illegal stimulant in the United States and is especially prevalent in Midwestern states. The sense of euphoria caused by the drug, the ease of manufacturing and the relatively low cost make it a drug of choice for many. The broad range of systemic effects potentially caused by the use of this drug is wide reaching and can vary in degree and presentation from patient to patient. Abnormalities include cardiac and pulmonary disorders as well as observable integumentary problems, psychoses, CNS disturbances, problems associated with immunity and constitutional signs and symptoms. Health care providers need to be vigilant in their efforts to identify patients who may be users of meth and to identify any subtle abnormal findings that may be indicative of significant underlying systemic pathology. Questionnaires like the RAFFT (Relax, Alone, Forget, Friends, Trouble) and the MINI (Mini-International Neuropsychiatric Interview) can be helpful in identifying substance abuse disorders in patients.

  12. 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

  13. Methamphetamine use and criminal behavior.

    PubMed

    Gizzi, Michael C; Gerkin, Patrick

    2010-12-01

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

  14. Methamphetamine: here we go again?

    PubMed

    Maxwell, Jane Carlisle; Brecht, Mary-Lynn

    2011-12-01

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Resolution of methamphetamine stereoisomers in urine drug testing: urinary excretion of R(-)-methamphetamine following use of nasal inhalers.

    PubMed

    Fitzgerald, R L; Ramos, J M; Bogema, S C; Poklis, A

    1988-01-01

    The objective of this study is to determine whether R(-)-methamphetamine inhaled from nasal inhalers produces positive methamphetamine results in currently used urine drug screening procedures and to present a rapid method for distinguishing the optical isomers of methamphetamine. Urine from three subjects inhaling from a Vicks Nasal Inhaler every 20 min for six hours tested positive for methamphetamine by EMIT, Toxilab, TDx, and GC/MS. The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (L-TPC) was used to form methamphetamine diastereomers allowing rapid identification of each stereoisomer of methamphetamine present in the urine samples. Urine samples positive for amphetamines during routine drug screening were determined to consist of a racemic mixture of methamphetamine. The isomeric composition of methamphetamine present in a urine sample indicates the probable source of the drug.

  16. 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…

  17. 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…

  18. On the Role of Imitation on Adolescence Methamphetamine Abuse Dynamics.

    PubMed

    Mushanyu, J; Nyabadza, F; Muchatibaya, G; Stewart, A G R

    2017-03-01

    Adolescence methamphetamine use is an issue of considerable concern due to its correlation with later delinquency, divorce, unemployment and health problems. Understanding how adolescents initiate methamphetamine abuse is important in developing effective prevention programs. We formulate a mathematical model for the spread of methamphetamine abuse using nonlinear ordinary differential equations. It is assumed that susceptibles are recruited into methamphetamine use through imitation. An epidemic threshold value, [Formula: see text], termed the abuse reproduction number, is proposed and defined herein in the drug-using context. The model is shown to exhibit the phenomenon of backward bifurcation. This means that methamphetamine problems may persist in the population even if [Formula: see text] is less than one. Sensitivity analysis of [Formula: see text] was performed to determine the relative importance of different parameters in methamphetamine abuse initiation. The model is then fitted to data on methamphetamine users less than 20 years old reporting methamphetamine as their primary substance of abuse in the treatment centres of Cape Town and parameter values that give the best fit are chosen. Results show that the proportion of methamphetamine users less than 20 years old reporting methamphetamine as their primary substance of abuse will continue to decrease in Cape Town of South Africa. The results suggest that intervention programs targeted at reducing adolescence methamphetamine abuse, are positively impacting methamphetamine abuse.

  19. Creatine as a Novel Treatment for Depression in Females Using Methamphetamine: A Pilot Study.

    PubMed

    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

    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. Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8-week open label trial of 5 g of daily creatine monohydrate and of these 14, 11 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. 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 positive urine drug screens of

  20. 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

  1. Effect of methamphetamine neurotoxicity on learning-induced Arc mRNA expression in identified striatal efferent neurons.

    PubMed

    Daberkow, David P; Riedy, Matthew D; Kesner, Raymond P; Keefe, Kristen A

    2008-12-01

    Methamphetamine abuse results in lasting, partial depletions of striatal dopamine and cognitive dysfunction. However, the effect of partial dopamine depletions on the expression of an effector immediate early gene, Arc (activity regulated, cytoskeletal-associated protein), known to be involved in synaptic modifications underlying learning and memory, has heretofore not been examined. Male Sprague-Dawley rats were pretreated with a neurotoxic regimen of methamphetamine or saline. Seven weeks later, rats were trained in a motor-response task on a T-maze for five days, and then underwent reversal training on day five. Rats were sacrificed 5 min after reaching criterion on the reversal task, and the brains were removed and processed using double-label fluorescent in situ hybridization for Arc and preproenkephalin (PPE) mRNA expression in the dorsomedial striatum. Rats pretreated with methamphetamine had an average (+/-SEM) 54.4+/-7.9% loss of dopamine in dorsomedial striatum. Interestingly, there was no difference in reversal trials to criterion in methamphetamine- vs. saline-pretreated rats. However, the expression of Arc mRNA in dorsomedial striatum was attenuated in methamphetamine-pretreated animals, particularly in PPE-negative neurons. Furthermore, the correlation between Arc mRNA expression in dorsomedial striatum and learning was abolished in methamphetamine-pretreated animals. These data suggest that methamphetamine-induced partial monoamine loss is associated with disrupted induction of the effector immediate early gene Arc during a behavioral task, particularly in PPE-negative (presumed striatonigral) neurons, as well as with disruption of the relation between Arc mRNA expression in dorsomedial striatum and reversal learning.

  2. Impairments in timing, temporal memory, and reversal learning linked to neurotoxic regimens of methamphetamine intoxication.

    PubMed

    Cheng, Ruey-Kuang; Etchegaray, Mikel; Meck, Warren H

    2007-12-01

    Methamphetamine intoxication has long-term consequences on dopaminergic function and corticostriatal-mediated behaviors in humans and other animals. In order to determine the potential impact on timing and temporal memory, we examined methamphetamine dose regimens that have been linked to neurotoxicity in adult (8 months) male rats. Rats that were given repetitive, high-dose methamphetamine (3.0 mg/kg ip x 4 injections/2 h) or saline injections were trained on a 2-s vs 8-s bisection procedure using auditory and visual signal durations. Following the high-dose regimen, baseline timing performance was reestablished prior to the rats' receiving reversal training in which the spatial/temporal mapping of the anchor durations (2 s and 8 s) to response options (left or right lever) was reversed. Low-dose methamphetamine (0.5 mg/kg ip) or saline injections were subsequently used to evaluate the effectiveness of the neurotoxic doses in terms of modifying the horizontal leftward shifts associated with increases in clock speed. Overall, the results indicate that MAP intoxication leads to reduced auditory/visual differences in clock speed, deficits in reversal learning, distortions in temporal memory, and lowered dopaminergic regulation of clock speed consistent with damage to prefrontal cortex and corticostriatal circuitry.

  3. Meal schedule influences food restriction-induced locomotor sensitization to methamphetamine

    PubMed Central

    Sharpe, Amanda L.; Klaus, Joshua D.

    2015-01-01

    Rationale Traditional protocols for inducing sensitization to psychostimulants use an intermittent or “binge”-like drug administration, and binge eating behavior is comorbid with drug abuse in humans. Food restriction increases the reinforcing properties and self-administration of many drugs of abuse. Objective The present study tested the hypotheses that (1) food restriction induces sensitization to the locomotor stimulation observed in response to methamphetamine and (2) a binge-like feeding schedule during food restriction produces increased sensitization compared to equally restricted mice fed in three daily meals. Methods Male DBA/2J mice were fed ad libitum or were food restricted to either an 8% or 16% loss of body weight. Additionally, the food-restricted mice were divided into two groups that were fed in either one meal (binge) or three equal-sized meals (meal). After the reduced body weight was stable, mice were tested for locomotor activity following saline and methamphetamine (1 mg/kg) injections. Results Both 16% body weight loss groups exhibited sensitization to methamphetamine. Opposite to our hypothesis, the 8% meal but not the 8% binge food-restricted group demonstrated locomotor sensitization. Serum corticosterone levels were significantly higher in the meal-fed groups when compared to the binge- and ad libitum-fed groups. Conclusions These results support a role for feeding schedule and plasma corticosterone levels in food restriction-induced enhancement of the effects of methamphetamine. PMID:21750897

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

    PubMed

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

    2017-05-12

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

  5. Adolescent methamphetamine use and sexual risk behaviour in secondary school students in Cape Town, South Africa.

    PubMed

    Plüddemann, Andreas; Flisher, Alan J; Mathews, Catherine; Carney, Tara; Lombard, Carl

    2008-11-01

    This study investigated involvement in substance use and sexual activities among adolescents in Cape Town, and specifically the associations between methamphetamine use and sexual risk behaviours. Data were collected from 15 randomly selected and 15 matched schools in Cape Town via quantitative questionnaires. Students used hand-held computers (PDAs) to answer the questions. A total of 4605 grade 9 students were sampled. Male and female students were almost equally likely to have used methamphetamine at least once (13% versus 12%). Students who had used methamphetamine in the past 30 days were significantly more likely to have had vaginal, anal or oral sex than students who had never used it, to have been pregnant/been responsible for a pregnancy and to have been diagnosed with a sexually transmitted infection. Logistic regression analysis indicated significant associations between methamphetamine use in the past 12 months and engaging in vaginal and anal sex. Drug abuse and sexually transmitted infections (STI) prevention services should incorporate the link between drugs and STI into their prevention and education strategies, especially those aimed at school-going adolescents.

  6. Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.

    PubMed

    Schindler, Charles W; Gilman, Joanne P; Panlilio, Leigh V; McCann, David J; Goldberg, Steven R

    2011-02-01

    The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 - 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.

  7. 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.

  8. Chlormethiazole potentiates the discriminative stimulus effects of methamphetamine in rats.

    PubMed

    Gasior, Maciej; Witkin, Jeffrey M; Goldberg, Steven R; Munzar, Patrik

    2004-06-28

    Chlormethiazole is a positive modulator of gamma-aminobutyric acid (GABA)(A) receptors used in the treatment of alcohol withdrawal seizures. It recently has been reported to attenuate seizures engendered by acute and repeated exposure to cocaine in mice and neurotoxic effects of methamphetamine in rats. The aim of the present study was to determine whether chlormethiazole could also attenuate the discriminative stimulus effects of methamphetamine, a behavior predictive of the subjective effects of methamphetamine in humans. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine [intraperitoneally (i.p.)] from saline under a fixed-ratio schedule of food delivery, the ability of chlormethiazole (i.p.) to (1) substitute for methamphetamine, (2) antagonize effects of methamphetamine and to (3) shift the methamphetamine dose-effect function was investigated. Chlormethiazole (18 and 30 mg/kg, i.p.) partially substituted for the discriminative stimulus effects of methamphetamine when administered alone (maximum group average, 60% responses on the methamphetamine-appropriate lever). Chlormethiazole did not attenuate effects of methamphetamine when coadministered with the training dose of methamphetamine. Instead, chlormethiazole potentiated the discriminative stimulus effects of methamphetamine as demonstrated by a significant (about 2.5-fold) leftward and upward shift in the methamphetamine dose-effect function in the presence of chlormethiazole (10 mg/kg). In conclusion, the present findings suggest that there is a behavioral interaction between methamphetamine and chlormethiazole. The profile of this interaction is qualitatively different from that of methamphetamine and classical GABAergic drugs (i.e., benzodiazepines and barbiturates), suggesting the involvement of non-GABAergic mechanisms in the effects produced by chlormethiazole.

  9. Neither non-contingent electric footshock nor administered corticosterone facilitate the acquisition of methamphetamine self-administration.

    PubMed

    Moffett, M C; Goeders, N E

    2005-02-01

    Previous research has indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the acquisition of intravenous cocaine self-administration since both exposure to stressors and exogenous injections of corticosterone facilitate this behavior. The present experiment was designed to determine whether electric footshock or pretreatment with corticosterone would produce similar effects on the acquisition of methamphetamine self-administration in male Wistar rats. Following initial food training, the rats were allowed to self-administer methamphetamine in ascending doses (0.0075-0.12 mg/kg/infusion) that were doubled weekly. Neither non-contingent electric footshock nor treatment with corticosterone (2.0 mg/kg, i.p.) affected the lowest dose at which the rats first acquired methamphetamine self-administration (0.015 mg/kg/infusion). The treatment groups all had similar inverted "U"-shaped acquisition curves typical of psychostimulants. Although these experiments do not indicate a major role for the HPA axis in the acquisition of methamphetamine self-administration, more studies need to be conducted to further evaluate the effects of the HPA axis on the acquisition of methamphetamine self-administration before a potential role can be ruled out.

  10. Increased expression of proenkephalin and prodynorphin mRNAs in the nucleus accumbens of compulsive methamphetamine taking rats.

    PubMed

    Cadet, Jean Lud; Krasnova, Irina N; Walther, Donna; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T; Collector, Daniel; Torres, Oscar V; Terry, Ndeah; Jayanthi, Subramaniam

    2016-11-14

    Addiction is associated with neuroadaptive changes in the brain. In the present paper, we used a model of methamphetamine self-administration during which we used footshocks to divide rats into animals that continue to press a lever to get methamphetamine (shock-resistant) and those that significantly reduce pressing the lever (shock-sensitive) despite the shocks. We trained male Sprague-Dawley rats to self-administer methamphetamine (0.1 mg/kg/infusion) for 9 hours daily for 20 days. Control group self-administered saline. Subsequently, methamphetamine self-administration rats were punished by mild electric footshocks for 10 days with gradual increases in shock intensity. Two hours after stopping behavioral experiments, we euthanized rats and isolated nucleus accumbens (NAc) samples. Affymetrix Array experiments revealed 24 differentially expressed genes between the shock-resistant and shock-sensitive rats, with 15 up- and 9 downregulated transcripts. Ingenuity pathway analysis showed that these transcripts belong to classes of genes involved in nervous system function, behavior, and disorders of the basal ganglia. These genes included prodynorphin (PDYN) and proenkephalin (PENK), among others. Because PDYN and PENK are expressed in dopamine D1- and D2-containing NAc neurons, respectively, these findings suggest that mechanisms, which impact both cell types may play a role in the regulation of compulsive methamphetamine taking by rats.

  11. Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.

    PubMed

    Carson, Dean S; Hunt, Glenn E; Guastella, Adam J; Barber, Lachlan; Cornish, Jennifer L; Arnold, Jonathon C; Boucher, Aurelie A; McGregor, Iain S

    2010-10-01

    Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.

  12. Increased expression of proenkephalin and prodynorphin mRNAs in the nucleus accumbens of compulsive methamphetamine taking rats

    PubMed Central

    Cadet, Jean Lud; Krasnova, Irina N.; Walther, Donna; Brannock, Christie; Ladenheim, Bruce; McCoy, Michael T.; Collector, Daniel; Torres, Oscar V.; Terry, Ndeah; Jayanthi, Subramaniam

    2016-01-01

    Addiction is associated with neuroadaptive changes in the brain. In the present paper, we used a model of methamphetamine self-administration during which we used footshocks to divide rats into animals that continue to press a lever to get methamphetamine (shock-resistant) and those that significantly reduce pressing the lever (shock-sensitive) despite the shocks. We trained male Sprague-Dawley rats to self-administer methamphetamine (0.1 mg/kg/infusion) for 9 hours daily for 20 days. Control group self-administered saline. Subsequently, methamphetamine self-administration rats were punished by mild electric footshocks for 10 days with gradual increases in shock intensity. Two hours after stopping behavioral experiments, we euthanized rats and isolated nucleus accumbens (NAc) samples. Affymetrix Array experiments revealed 24 differentially expressed genes between the shock-resistant and shock-sensitive rats, with 15 up- and 9 downregulated transcripts. Ingenuity pathway analysis showed that these transcripts belong to classes of genes involved in nervous system function, behavior, and disorders of the basal ganglia. These genes included prodynorphin (PDYN) and proenkephalin (PENK), among others. Because PDYN and PENK are expressed in dopamine D1- and D2-containing NAc neurons, respectively, these findings suggest that mechanisms, which impact both cell types may play a role in the regulation of compulsive methamphetamine taking by rats. PMID:27841313

  13. 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

  14. 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

  15. 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.

  16. Accidental death via intravaginal absorption of methamphetamine.

    PubMed

    Jones, Prentiss; Mutsvunguma, Romeo; Prahlow, Joseph A

    2014-06-01

    In this paper a drug fatality that involved an unintended drug delivery route is described. The decedent, a 23-year-old female in custody in a county jail on suspicion of a felony drug offense, was discovered in a holding cell unconscious and unresponsive. Following unsuccessful cardiopulmonary resuscitation attempts she was pronounced dead at the scene. At autopsy a wad of multiple small loosely wrapped plastic packages held together with another layer of clear plastic was found in the decedent's vagina. The smaller plastic packages contained an off-white pasty substance that was later identified as methamphetamine. Toxicological testing of specimens collected during autopsy revealed methamphetamine in the decedent's subclavian blood, vitreous fluid, and urine at extremely high concentrations (42.6, 20.1, and 771 mg/L, respectively). Amphetamine, the active metabolite of methamphetamine, was also present in the subclavian blood, vitreous fluid, and urine at significant concentrations (1.3, 0.5, and 20.4 mg/L, respectively). The cause of death was attributed to toxic effects of methamphetamine and the manner of death was ruled accidental. This report suggests that lethal concentrations of methamphetamine may be distributed to the systemic circulation via intravaginal absorption.

  17. Methamphetamine

    MedlinePlus

    ... skin sores from scratching anxiety confusion sleeping problems violent behavior paranoia —extreme and unreasonable distrust of others ... intense itching, leading to skin sores from scratching; violent behavior; and paranoia. Researchers don't yet know ...

  18. Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A2A receptor-independent mechanism.

    PubMed

    Zanos, Panos; Wright, Sherie R; Georgiou, Polymnia; Yoo, Ji Hoon; Ledent, Catherine; Hourani, Susanna M; Kitchen, Ian; Winsky-Sommerer, Raphaelle; Bailey, Alexis

    2014-04-01

    There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergic system is dysregulated following chronic methamphetamine administration. We tested this hypothesis by examining the effect of chronic methamphetamine administration on oxytocin receptor density in mice brains with the use of quantitative receptor autoradiographic binding. Saline (4ml/kg/day, i.p.) or methamphetamine (1mg/kg/day, i.p.) was administered daily for 10 days to male, CD1 mice. Quantitative autoradiographic mapping of oxytocin receptors was carried out with the use of [(125)I]-vasotocin in brain sections of these animals. Chronic methamphetamine administration induced a region specific upregulation of oxytocin receptor density in the amygdala and hypothalamus, but not in the nucleus accumbens and caudate putamen. As there is evidence suggesting an involvement of central adenosine A2A receptors on central endogenous oxytocinergic function, we investigated whether these methamphetamine-induced oxytocinergic neuroadaptations are mediated via an A2A receptor-dependent mechanism. To test this hypothesis, autoradiographic oxytocin receptor binding was carried out in brain sections of male CD1 mice lacking A2A receptors which were chronically treated with methamphetamine (1mg/kg/day, i.p. for 10 days) or saline. Similar to wild-type animals, chronic methamphetamine administration induced a region-specific upregulation of oxytocin receptor binding in the amygdala and hypothalamus of A2A receptor knockout mice and no genotype effect was observed. These results indicate that chronic methamphetamine use can induce profound neuroadaptations of the oxytocinergic receptor

  19. Could sigma receptor ligands be a treatment for methamphetamine addiction?

    PubMed

    Rodvelt, Kelli R; Miller, Dennis K

    2010-09-01

    Methamphetamine's effects are generally considered to be mediated via monoamine transporters; however, it has comparable affinity for sigma receptors. Sigma receptors influence the downstream dopamine systems that are targeted by methamphetamine treatment. Research investigating the effect of sigma receptor agonists on methamphetamine-associated neurochemical and behavioral properties remains controversial; however, the general trend indicates an enhancement of stimulant effects. In contrast, sigma receptor antagonists attenuate methamphetamine-induced neurotoxic and behavioral properties. Together, these studies highlight an important role for sigma receptors in methamphetamine's addictive properties and the consequences of methamphetamine intoxication. Additional research is necessary to elucidate the precise mechanisms underlying their involvement and their role as a potential target for anti-methamphetamine pharmacotherapies.

  20. Methamphetamine use in nonurban and urban drug court clients.

    PubMed

    Stoops, William W; Tindall, Michele Staton; Mateyoke-Scrivner, Allison; Leukefeld, Carl

    2005-06-01

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

  1. A 42-year-old patient presenting with femoral head migration after hemiarthroplasty performed 22 years earlier: a case report.

    PubMed

    Kanda, Akio; Kaneko, Kazuo; Obayashi, Osamu; Mogami, Atsuhiko

    2015-01-15

    Treatment of femoral neck fractures in young adults may require total hip arthroplasty or hip hemiarthroplasty using a bipolar cup. The latter can, however, result in migration of the femoral head and poor long-term results. We report a case of femoral head migration after hemiarthroplasty performed for femoral neck fracture that had occurred 22 years earlier, when the patient (a Japanese man) was 20 years old. He experienced peri-prosthetic fracture of the femur, subsequent migration of the prosthesis, and a massive bone defect of the pelvic side acetabular roof. After bone union of the femoral shaft fracture, the patient was referred to our hospital for reconstruction of the acetabular roof. Intra-operatively, we placed two alloimplants of bone from around the transplanted femoral head into the weight-bearing region of the acetabular roof using an impaction bone graft method. We then implanted an acetabular roof reinforcement plate and a cemented polyethylene cup in the position of the original acetabular cup. Eighteen months post-operatively, X-rays showed union of the transplanted bone. Treatment of femoral neck fractures in young adults is usually accomplished by osteosynthesis, but it may be complicated by femoral head avascular necrosis or by infection or osteomyelitis. In such cases, once an infection has subsided, either hip hemiarthroplasty using a bipolar cup or total hip arthroplasty may be required. However, if the acetabular side articular cartilage is damaged, a bipolar cup should not be used. Total hip arthroplasty should be performed to prevent migration of the implant.

  2. 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

  3. Clinical Course of Methamphetamine-Induced Psychotic Disorder in a 3-Month Follow-Up.

    PubMed

    Javadian, Sakineh; Shabani, Amir; Shariat, Seyed Vahid

    2016-11-03

    To assess the clinical course of patients with methamphetamine-induced psychotic disorder (MIPD) and any possible predictors of the clinical course in a 3-month follow-up. This prospective cohort study included 50 patients (7 female, 43 male) with MIPD and was performed from September 2014 to October 2015. Patients were assessed during hospitalization and in a follow-up visit 3 months later. Diagnoses were made using interviews based on the Structured Clinical Interview for DSM-IV Axis I Disorders. Positive, negative, manic, and depressive symptoms were the main outcome measures that were assessed using the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Young Mania Rating Scale, and Hamilton Depression Rating Scale, respectively. Paired t test and regression analysis were used to analyze the data. Forty-six patients (92%) were reassessed at follow-up. More than half of the patients relapsed to methamphetamine use, did not adhere to treatment, and were functionally impaired. Positive, negative, and manic symptoms, but not depressive symptoms, improved in abstinent patients (P < .001, P = .001, P < .001, and P = .395, respectively). The best predictor of depressive and negative symptoms at follow-up was the patients' respective baseline scores; but positive and manic symptoms were best predicted by reuse of methamphetamine during follow-up. Various symptom categories do not always change in the same direction during the course of the disorder, especially depressive symptoms that do not improve with abstinence but aggravate with frequency of methamphetamine use. Negative symptoms at baseline also seem to have a possible role in prediction of methamphetamine reuse in patients with MIPD. Physicians should be advised to independently address all of the symptom categories of their patients with MIPD at each follow-up visit.

  4. Cocaine and methamphetamine induce opposing changes in BOLD signal response in rats.

    PubMed

    Taheri, Saeid; Xun, Zhu; See, Ronald E; Joseph, Jane E; Reichel, Carmela M

    2016-07-01

    Neuroimaging studies in psychostimulant addicts have reported functional neural activity changes in brain regions involved in relapse. However, the difference between the effects of the psychostimulants methamphetamine and cocaine on neuronal activity in a similar setting not been clarified. Since studies in humans are limited by the inability to study the initial impact of psychostimulant drugs, we addressed this issue in a rat model. Here, we report methamphetamine and cocaine-induced blood-oxygen-level dependent (BOLD) signal change using functional magnetic resonance imaging (fMRI) in rats receiving drug for the first time during the imaging session. Twenty-three male Long Evans rats underwent fMRI imaging and received an intravenous infusion of methamphetamine, cocaine, or saline. Anatomical and pharmacological fMRI (pfMRI) were performed on a 7T BioSpec dedicated research MR scanner under isoflurane gas (1.5-2%). After collecting baseline data for 10min, rats received drug over the next 10min for a total 40min scan time. Data were then preprocessed and statistically analyzed in anatomically defined regions of interest (ROIs) that have been implicated in persistent drug seeking and relapse. Methamphetamine during the imaging session resulted in a sustained negative BOLD signal change in key regions of the relapse circuit, except for the prefrontal cortex. In contrast, cocaine evoked a positive or unchanged BOLD signal in these same regions. In all of the investigated ROIs, there were no changes in BOLD signal following saline. Acute methamphetamine and cocaine have distinct patterns of functional activity as measured by pfMRI. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Acute liver failure following intravenous methamphetamine.

    PubMed

    Kamijo, Yoshito; Soma, Kazui; Nishida, Manami; Namera, Akira; Ohwada, Takashi

    2002-08-01

    A 41-y-o Pakistani man presented with psychosis, hyperthermia, rhabdomyolysis, and liver dysfunction approximately 6 h after i.v. injection of methamphetamine. Serum concentrations of methamphetamine and amphetamine on admission were 0.30 microg/mL and 0.04 microg/mL, respectively. Total serum bilirubin and alanine aminotransferase concentrations peaked on the 3rd hospital day at 8.6 mg/dL and 4155 IU/L, respectively, and gradually returned to normal with supportive care. The patient had no evidence of infectious hepatitis or intake of other drugs. Histologic examination of a liver biopsy specimen obtained on the 11th d showed confluent necrosis and ballooning degeneration in centrilobular zones. No inflammatory changes were seen in portal tracts. Liver damage can be a complication of illicit methamphetamine use, even in patients without viral infection or intake of other drugs.

  6. Neurobehavioral Effects from Developmental Methamphetamine Exposure.

    PubMed

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

    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.

  7. 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

  8. Methamphetamine intoxication in a dog: case report.

    PubMed

    Pei, Zengyang; Zhang, Xu

    2014-06-24

    Methamphetamine abuse has undergone a dramatic worldwide increase, and represents a significant and global issue for public health. Incidents of methamphetamine intoxication and death in humans are relatively commonplace. Because of its increasing illicit availability, together with legitimate use in human medicine, accidental or intentional exposure to methamphetamine in dogs is becoming a more likely scenario. A 3-year-old, 3.7 kg intact female Miniature Poodle who had been intentionally fed an unknown amount of a crystalline-like substance developed extreme agitation, seizures, tachycardia, hyperthermia, hypertension, disseminated intravascular coagulation (DIC), bloody diarrhea, and dilated pupils. Blood work revealed leukocytosis, erythropenia, lymphocytosis, thrombocytopenia, coagulation abnormalities, but all to a mild extent, together with mild elevation in both alanine aminotranferease (ALT) and alkaline phosphatase (ALKP), and a mild decreased in glucose. Radiologic diagnosis revealed generalized, severe distension of the stomach and small intestinal tract with air. Immunochromatographic screening tests and gas chromatography mass spectrometry analysis confirmed methamphetamine intoxication and revealed concentrations of methamphetamine in blood and urine of 0.32 μg/mL and 2.35 μg/mL respectively. The dog demonstrated progressive improvement after supportive care, with the high fever resolved over the initial 24 hours of hospitalization, and agitation was successfully controlled beyond 48 hours after initial hospitalization. Hemostatic abnormalities were progressive improved after heparin therapy and supportive care. By the sixth day of hospitalization the dog was clinically well, and all laboratory data had returned to normal with the exception of a mild elevateion of ALKP. To the authors' knowledge, this is the second case report of methamphetamine intoxication in dogs presented in veterinary practice in open literature so far. Although rare

  9. Methamphetamine-induced sensitization is associated with alterations to the proteome of the prefrontal cortex: implications for the maintenance of psychotic disorders.

    PubMed

    Wearne, Travis A; Mirzaei, Mehdi; Franklin, Jane L; Goodchild, Ann K; Haynes, Paul A; Cornish, Jennifer L

    2015-01-02

    Repeat administration of psychostimulants, such as methamphetamine, produces a progressive increase in locomotor activity (behavioral sensitization) in rodents that is believed to represent the underlying neurochemical changes driving psychoses. Alterations to the prefrontal cortex (PFC) are suggested to mediate the etiology and maintenance of these behavioral changes. As such, the aim of the current study was to investigate changes to protein expression in the PFC in male rats sensitized to methamphetamine using quantitative label-free shotgun proteomics. A methamphetamine challenge resulted in a significant sensitized locomotor response in methamphetamine pretreated animals compared to saline controls. Proteomic analysis revealed 96 proteins that were differentially expressed in the PFC of methamphetamine treated rats, with 20% of these being previously implicated in the neurobiology of schizophrenia in the PFC. We identified multiple biological functions in the PFC that appear to be commonly altered across methamphetamine-induced sensitization and schizophrenia, and these include synaptic regulation, protein phosphatase signaling, mitochondrial function, and alterations to the inhibitory GABAergic network. These changes could inform how alterations to the PFC could underlie the cognitive and behavioral dysfunction commonly seen across psychoses and places such biological changes as potential mediators in the maintenance of psychosis vulnerability.

  10. Alteration of catecholamine concentrations in rat testis after methamphetamine exposure.

    PubMed

    Janphet, S; Nudmamud-Thanoi, S; Thanoi, S

    2017-03-01

    Methamphetamine (METH) is an illicit drug that can lead to changes in catecholamines in the brain. It also has substantial effects on reproductive function. We investigated whether rat models of METH abuse could induce changes in the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its metabolite, 3,4-dihydroxyphenylglycol (DHPG), in testis. Four groups of rats received vehicle, acute dose (AB), escalating dose (ED) or ED with an acute high dose (ED-binge) METH. DOPAC, NE and DHPG were determined using HPLC. DOPAC was significantly increased in the AB while NE was significantly decreased in the ED-binge. DHPG was also significantly decreased in the ED and ED-binge. METH induces alterations of DOPAC, NE and DHPG testicular concentrations that may result in male reproductive dysfunction.

  11. Prenatal lead exposure enhances methamphetamine sensitization in rats.

    PubMed

    Clifford, P Shane; Hart, Nigel; Thompson, Jeff; Buckman, Sam; Wellman, Paul J; Bratton, Gerald R; Nation, Jack R

    2009-08-01

    Adult female rats were exposed to lead-free sodium acetate via gavage [0 mg (vehicle control)] or to 16 mg lead as lead acetate for 30 days prior to breeding. Following confirmation of breeding, the female animals continued to be exposed to their respective doses throughout gestation and lactation. When weaned, 16 control and 16 lead-exposed offspring were placed on regular water and food (lead-exposure was discontinued) until postnatal day (PND) 70. At this time, one-half of the control animals and one-half of the lead-treatment animals received intraperitoneal (i.p.) injections of the vehicle (saline) for 10 successive days and the remaining animals in each exposure conditions received daily injections of 1.0 mg/kg (+)-methamphetamine (METH) for 10 days (N=8/group). Locomotion in automated chambers was monitored daily for 45 min post-injection. Subsequently, during dose-effect testing, all animals received consecutive daily i.p. injections of 0, 1.0, 2.0, and then 4.0 mg/kg METH. The results of the experiment showed that both control and lead-exposed animals exhibited heightened locomotor activity (i.e. behavioral sensitization) to the repeated administration of 1.0 mg/kg METH. More importantly, animals developmentally (perinatally) exposed to lead showed more rapid sensitization than did their control counterparts. These data indicate that early lead exposure increases sensitivity to the locomotor-stimulating effects of METH. In contrast, identically exposed lead animals exhibit diminished METH dose-effect responding when tested in an intravenous (i.v.) self-administration paradigm [Rocha A., Valles R., Bratton G.R., Nation J.R. Developmental lead exposure alters methamphetamine self-administration in the male rat: acquisition and reinstatement. Drug Alcohol Depend 2008a;95:23-29, Rocha A., Valles R., Hart N., Bratton G.R., Nation J.R. Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio

  12. [Molecular mechanism for methamphetamine-induced memory impairment].

    PubMed

    Nagai, Taku; Yamada, Kiyofumi

    2010-04-01

    Methamphetamine is a highly addictive drug of abuse, addiction to which has increased to epidemic proportions worldwide. It has been suggested that chronic use of methamphetamine causes long-term cognitive deficits, in addition to psychiatric signs such as hallucination and delusions, which are indistinguishable from paranoid schizophrenia. Neuroimaging studies in methamphetamine abusers have demonstrated that the loss of dopamine transporters in the striatum is related to motor and cognitive impairment. In this review, we will focus on the effect of repeated treatment with methamphetamine on cognitive function in rodents. Repeated methamphetamine treatment in mice impairs long-term recognition memory after withdrawal, which is associated with the dysfunction in dopamine D1 receptor-extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the prefrontal cortex. Methamphetamine-induced impairment of recognition memory is reversed by baclofen, clozapine, minocycline and ZSET1446. Repeated methamphetamine treatment in rats also induces impairment of spatial working memory, which is accompanied by the dysfunction of ERK1/2 pathway in the hippocampus. Repeated administration of clozapine, but not haloperidol, improves methamphetamine-induced spatial working memory impairment. These findings suggest that ERK1/2 plays an important role in memory impairments induced by repeated methamphetamine treatment. These animal models of cognitive deficits may be useful to predict the clinical effects of antipsychotics in methamphetamine psychosis and other mental disorders such as schizophrenia.

  13. 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.

  14. 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. PMID:27275252

  15. Acute unilateral visual loss due to a single intranasal methamphetamine abuse.

    PubMed

    Wijaya, J; Salu, P; Leblanc, A; Bervoets, S

    1999-01-01

    An otherwise healthy 35 year old male with insulin-dependent diabetes mellitus (IDDM) presented himself three days after a single intranasal methamphetamine abusus. Directly upon awakening the day after the recreational use of this drug, he discovered an acute and severe visual loss of his right eye. This unilateral loss of vision was permanent and eventually lead to a pale and atrophic optic nerve head. The characteristics of this visual loss, together with the aspect of the optic nerve head was very similar to the classical non-arteritic ischemic optic neuropathy (NAION). We suggest a direct ischemic episode to the short posterior ciliary arteries due to this single intranasal abuse of methamphetamine as the underlying pathogenesis of this acute and permanent visual loss.

  16. 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…

  17. Powerful Behavioral Interactions Between Methamphetamine and Morphine

    PubMed Central

    Trujillo, Keith A.; Smith, Monique L.; Guaderrama, Melissa M.

    2011-01-01

    Use of drugs of abuse in combination is common among recreational users and addicts. The combination of a psychomotor stimulant with an opiate, known as a ‘speedball’, reportedly produces greater effects than either drug alone and has been responsible for numerous deaths. Historically, the most popular speedball combination is that of cocaine and heroin. However, with the growing popularity of methamphetamine in recent years, there has been increased use of this drug in combination with other drugs of abuse, including opiates. Despite this, relatively little research has examined interactions between methamphetamine and opiates. In the current research, behavioral interactions between methamphetamine and the prototypical opiate, morphine, were examined across a variety of dose combinations in Sprague-Dawley rats. The combination of methamphetamine and morphine produced stimulation of behavior that was dramatically higher than either drug alone; however, the magnitude of the interaction was dependent on the dose of the drugs and the specific behaviors examined. The results demonstrate complex behavioral interactions between these drugs, but are consistent with the idea that this combination is used because it produces a greater effect than either drug alone. PMID:21549146

  18. Tips for Teens: The Truth about Methamphetamine

    MedlinePlus

    ... than it’s meant to go. It increases the heart rate, blood pressure, and risk of stroke. Methamphetamine affects your self- ... confusion • Extreme anorexia • Tremors or even convulsions • Increased heart rate,blood pressure,and risk of stroke • Presence of inhaling paraphernalia, ...

  19. 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…

  20. 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…

  1. 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…

  2. Hippocampal leptin suppresses methamphetamine-induced hyperlocomotion.

    PubMed

    Nishio, Masahiro; Watanabe, Yasuhiro

    2010-10-01

    Leptin is an anorexigenic peptide which is synthesized in white adipose tissue. The actions of leptin are mediated by the leptin receptor which is abundantly localized in the hypothalamus and is involved in energy regulation and balance. Recently, there has been evidence suggesting that the leptin receptor is also present in the hippocampus and may be involved with hippocampal excitability and long-term depression. To investigate the physiological function of leptin signalling in the hippocampus, we studied the effects of leptin on methamphetamine-induced ambulatory hyperactivity by utilizing intra-hippocampal infusion (i.h.) in mice. Our results show that the infusion of leptin (5 ng each bilaterally i.h.) does not affect the basal ambulatory activity but significantly suppresses methamphetamine-induced ambulatory hyperactivity as compared to saline-infused controls. Interestingly, higher dose of leptin increases the suppression of the methamphetamine-induced ambulatory hyperactivity. The i.h. infusion of leptin did not activate the JAK-STAT pathway, which is the cellular signalling pathway through which leptin acts in the hypothalamus. The infusion of leptin also did not affect activation of p42/44 MAPK which is known to be another leptin-induced signalling pathway in the brain. These results demonstrate that leptin has a novel potential suppressive effect on methamphetamine-induced hyperlocomotion and also suggest that there must be an alternative pathway in the hippocampus through which leptin signalling is being mediated.

  3. 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

  4. A comparison of pattern of psychiatric symptoms in inpatients with bipolar disorder type one with & without methamphetamine use.

    PubMed

    Gouran Ourimi, Elham; Shabani, Amir; Alavi, Kaveh; Najarzadegan, Mohammad Reza; Mirfazeli, Fatemehsadat

    2016-01-01

    Background: Iran is facing an outbreak of methamphetamine-induced disorders and frequent use of these substances in patients with bipolar disorder. Using or intoxication of methamphetamine in patients with bipolar I disorder may alter the patient's clinical profile; however there is limited studies about impact of methamphetamine on clinical manifestation of bipolar disorders. This study aimed to compare psychiatric symptoms in patients with bipolar I disorder with and without concomitant use of methamphetamine. Methods: In a cross-sectional study, psychiatric symptoms of bipolar I disorder in patients with (Meth+) and without (Meth-) methamphetamine use was evaluated. A number of 57 participants with Meth + and 50 subjects with Meth- were recruited. The clinical picture of bipolar disorder was investigated by Young Mania Rating Scale (YMRS), 17-item Hamilton Depressive Rating Scale (HDRS-17) and the Scale for Assessment of Positive Symptoms (SAPS). Statistical comparisons were performed using the T-test for independent samples and Mann- Whitney test. Results: There was no statistically significant difference between two groups regarding age, duration of illness and hospitalizations. However, male participants were significantly higher in Meth+ group than in Meth- one (p<0.001). The mean (± SD) scores in the two groups of Meth+ and Meth- for YMRS, HDRS, and SAPS were 31.3 (±1.3) and 34.0 (±1.2), 13.7 (±0.7) and 13.5±(0.5), and 50.0 (±1.9) and 48.0 (±2.1), respectively, which were not statistically significant (p<0.05). Conclusion: There was no significant difference in the overall clinical manifestation of bipolar I disorder in patients with and without methamphetamine use. However, in some symptomatology domains, there were some differences between the two groups.

  5. A comparison of pattern of psychiatric symptoms in inpatients with bipolar disorder type one with & without methamphetamine use

    PubMed Central

    Gouran Ourimi, Elham; Shabani, Amir; Alavi, Kaveh; Najarzadegan, Mohammad Reza; Mirfazeli, Fatemehsadat

    2016-01-01

    Background: Iran is facing an outbreak of methamphetamine-induced disorders and frequent use of these substances in patients with bipolar disorder. Using or intoxication of methamphetamine in patients with bipolar I disorder may alter the patient's clinical profile; however there is limited studies about impact of methamphetamine on clinical manifestation of bipolar disorders. This study aimed to compare psychiatric symptoms in patients with bipolar I disorder with and without concomitant use of methamphetamine. Methods: In a cross-sectional study, psychiatric symptoms of bipolar I disorder in patients with (Meth+) and without (Meth-) methamphetamine use was evaluated. A number of 57 participants with Meth + and 50 subjects with Meth- were recruited. The clinical picture of bipolar disorder was investigated by Young Mania Rating Scale (YMRS), 17-item Hamilton Depressive Rating Scale (HDRS-17) and the Scale for Assessment of Positive Symptoms (SAPS). Statistical comparisons were performed using the T-test for independent samples and Mann- Whitney test. Results: There was no statistically significant difference between two groups regarding age, duration of illness and hospitalizations. However, male participants were significantly higher in Meth+ group than in Meth- one (p<0.001). The mean (± SD) scores in the two groups of Meth+ and Meth- for YMRS, HDRS, and SAPS were 31.3 (±1.3) and 34.0 (±1.2), 13.7 (±0.7) and 13.5±(0.5), and 50.0 (±1.9) and 48.0 (±2.1), respectively, which were not statistically significant (p<0.05). Conclusion: There was no significant difference in the overall clinical manifestation of bipolar I disorder in patients with and without methamphetamine use. However, in some symptomatology domains, there were some differences between the two groups. PMID:28210586

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

    PubMed Central

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

    2009-01-01

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

  7. 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.

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

    PubMed Central

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

    2016-01-01

    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

  9. Methamphetamine influences on brain and behavior: unsafe at any speed?

    PubMed

    Marshall, John F; O'Dell, Steven J

    2012-09-01

    Methamphetamine damages monoamine-containing nerve terminals in the brains of both animals and human drug abusers, and the cellular mechanisms underlying this injury have been extensively studied. More recently, the growing evidence for methamphetamine influences on memory and executive function of human users has prompted studies of cognitive impairments in methamphetamine-exposed animals. After summarizing current knowledge about the cellular mechanisms of methamphetamine-induced brain injury, this review emphasizes research into the brain changes that underlie the cognitive deficits that accompany repeated methamphetamine exposure. Novel approaches to mitigating or reversing methamphetamine-induced brain and behavioral changes are described, and it is argued that the slow spontaneous reversibility of the injury produced by this drug may offer opportunities for novel treatment development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. A dissociation in attentional control: evidence from methamphetamine dependence.

    PubMed

    Salo, Ruth; Nordahl, Thomas E; Moore, Charles; Waters, Christy; Natsuaki, Yutaka; Galloway, Gantt P; Kile, Shawn; Sullivan, Edith V

    2005-02-01

    Selective attention comprises multiple, dissociable component processes, including task shifting and selective inhibition. The goal of this study was to test whether task-shifting, selective inhibition, or both processes were impaired in long-term but currently abstinent methamphetamine-dependent individuals. Participants were 34 methamphetamine-dependent subjects and 20 nonsubstance abusing controls who were tested on an alternating-runs switch task with conflict sequences that required subjects to switch tasks on every second trial (AABBAABB). Methamphetamine-dependent individuals committed more errors on trials that required inhibition of distracting information compared with controls (methamphetamine = 17%; controls = 13%; p = .02). By contrast, error rates did not differ between the groups on switch trials (methamphetamine = 7%; controls = 6%; p = .68). These results indicate that selective inhibition, but not task switching, is selectively compromised by methamphetamine.

  11. 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

  12. [Establishment and evaluation of animal model with methamphetamine poisoning].

    PubMed

    Xu, Jing; Zhou, Xiao-Li; Zhang, Hao; Deng, Chong; Zhang, Yan; Li, Zhen

    2009-08-01

    Amphetamine-type stimulants (ATS) is the most widespread narcotics in the 21st century. The methamphetamine's intoxication mechanism, psychological dependence, drug resistance and therapeutic drug development are the hot spots in current research. Establishment of animal model with methamphetamine poisoning is the basic for the relative studies, the normalization and standardization of the animal model settles the foundation for methamphetamine's further research. This article reviews the animal model of methamphetamine poisoning in China and abroad, the brief history of the acute, subacute and chronic animal model of methamphetamine poisoning, as well as the principles and methods of the animal model establishment and its evaluation criteria. The necessity, significance and its scientific expansion of performing experimental research on the methamphetamine poisoning animal model are also discussed.

  13. Sex-Specific Alterations of White Matter Developmental Trajectories in Infants With Prenatal Exposure to Methamphetamine and Tobacco.

    PubMed

    Chang, Linda; Oishi, Kenichi; Skranes, Jon; Buchthal, Steven; Cunningham, Eric; Yamakawa, Robyn; Hayama, Sara; Jiang, Caroline S; Alicata, Daniel; Hernandez, Antonette; Cloak, Christine; Wright, Tricia; Ernst, Thomas

    2016-12-01

    showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02). Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

  14. Methamphetamine enhances Hepatitis C virus replication in human hepatocytes.

    PubMed

    Ye, L; Peng, J S; Wang, X; Wang, Y J; Luo, G X; Ho, W Z

    2008-04-01

    Very little is known about the interactions between hepatitis C virus (HCV) and methamphetamine, which is a highly abused psychostimulant and a known risk factor for human immunodeficiency virus (HIV)/HCV infection. This study examined whether methamphetamine has the ability to inhibit innate immunity in the host cells, facilitating HCV replication in human hepatocytes. Methamphetamine inhibited intracellular interferon alpha expression in human hepatocytes, which was associated with the increase in HCV replication. In addition, methamphetamine also compromised the anti-HCV effect of recombinant interferon alpha. Further investigation of mechanism(s) responsible for the methamphetamine action revealed that methamphetamine was able to inhibit the expression of the signal transducer and activator of transcription 1, a key modulator in interferon-mediated immune and biological responses. Methamphetamine also down-regulated the expression of interferon regulatory factor-5, a crucial transcriptional factor that activates the interferon pathway. These in vitro findings that methamphetamine compromises interferon alpha-mediated innate immunity against HCV infection indicate that methamphetamine may have a cofactor role in the immunopathogenesis of HCV disease.

  15. Methamphetamine enhances histoplasmosis by immunosuppression of the host.

    PubMed

    Martinez, Luis R; Mihu, Mircea Radu; Gácser, Attila; Santambrogio, Laura; Nosanchuk, Joshua D

    2009-07-01

    The effect of methamphetamine on the host response to an opportunistic pathogen has not been extensively described. Methamphetamine is a major public health and safety problem in the United States. Chronic methamphetamine abuse is associated with a 2-fold higher risk of human immunodeficiency virus infection and, possibly, additional infections. Histoplasma capsulatum is a dimorphic fungus that is endemic in the Midwest of the United States and that causes respiratory and systemic disease, particularly in individuals with impaired immunity. We showed that methamphetamine abrogates normal macrophage function, resulting in an inability to control histoplasmosis. Methamphetamine decreased phagocytosis and killing of yeast by primary macrophages by alkalization of the phagosome. Furthermore, mice that received methamphetamine prior to H. capsulatum infection were immunologically impaired, with increased fungal burden, increased pulmonary inflammation, and decreased survival. Immunosuppression by methamphetamine may be associated with deregulation of cytokines in the lungs of infected mice, aberrant processing of H. capsulatum within macrophages, and immobilization of MAC-1 receptors on the surface of macrophages that are involved in phagocytosis. Additionally, methamphetamine inhibits T cell proliferation and alters antibody production, which are important components of adaptive immunity. With use of a murine model of histoplasmosis, this study establishes that methamphetamine may alter the immune system of the host and enhance fungal pathogenesis.

  16. Methamphetamine Causes Microglial Activation in the Brains of Human Abusers

    PubMed Central

    Sekine, Yoshimoto; Ouchi, Yasuomi; Sugihara, Genichi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Iwata, Yasuhide; Tsuchiya, Kenji J.; Suda, Shiro; Suzuki, Katsuaki; Kawai, Masayoshi; Takebayashi, Kiyokazu; Yamamoto, Shigeyuki; Matsuzaki, Hideo; Ueki, Takatoshi; Mori, Norio; Gold, Mark S.; Cadet, Jean L.

    2008-01-01

    Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [11C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([11C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [11C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [11C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (> 250% higher, p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence. PMID:18509037

  17. The methamphetamine home: psychological impact on preschoolers in rural Tennessee.

    PubMed

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

    2008-01-01

    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. To examine whether preschoolers who lived in methamphetamine-producing homes are at increased risk for developing psychological problems. The participants were 58 white children between the ages of 4 and 5 years; 31 with a history of living in methamphetamine-producing homes and 27 children who live in non-methamphetamine producing homes in rural Tennessee. The groups were similar in age, gender, and socioeconomic background. The groups were compared for behavioral and emotional adjustment using the behavior assessment system for children-parent rating scale-preschool (BASC-PRS-P) form. Biological or custodian parents completed a rating on their preschoolers that provided information about the children's pattern of behavior and feelings. Preschoolers from the methamphetamine-producing homes showed more externalizing problems than their peers, but were comparable on internalizing problems. On specific behaviors, the data indicate that preschoolers in the methamphetamine group showed higher aggression symptoms than their peers from non-methamphetamine-producing homes. These findings, if replicated, point to the need for mental health screening when a child is removed from a methamphetamine-producing home.

  18. Methamphetamine enhances Hepatitis C virus replication in human hepatocytes

    PubMed Central

    Ye, L.; Peng, J. S.; Wang, X.; Wang, Y. J.; Luo, G. X.; Ho, W. Z.

    2009-01-01

    SUMMARY Very little is known about the interactions between hepatitis C virus (HCV) and methamphetamine, which is a highly abused psychostimulant and a known risk factor for human immunodeficiency virus (HIV)/HCV infection. This study examined whether methamphetamine has the ability to inhibit innate immunity in the host cells, facilitating HCV replication in human hepatocytes. Methamphetamine inhibited intracellular interferon alpha expression in human hepatocytes, which was associated with the increase in HCV replication. In addition, methamphetamine also compromised the anti-HCV effect of recombinant interferon alpha. Further investigation of mechanism(s) responsible for the methamphetamine action revealed that methamphetamine was able to inhibit the expression of the signal transducer and activator of transcription 1, a key modulator in interferon-mediated immune and biological responses. Methamphetamine also down-regulated the expression of interferon regulatory factor-5, a crucial transcriptional factor that activates the interferon pathway. These in vitro findings that methamphetamine compromises interferon alpha-mediated innate immunity against HCV infection indicate that methamphetamine may have a cofactor role in the immunopathogenesis of HCV disease. PMID:18307590

  19. Involvement of PUMA in pericyte migration induced by methamphetamine.

    PubMed

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

    2017-07-01

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

  20. Impaired arterial smooth muscle cell vasodilatory function in methamphetamine users.

    PubMed

    Nabaei, Ghaemeh; Oveisgharan, Shahram; Ghorbani, Askar; Fatehi, Farzad

    2016-11-15

    Methamphetamine use is a strong risk factor for stroke. This study was designed to evaluate arterial function and structure in methamphetamine users ultrasonographically. In a cross-sectional study, 20 methamphetamine users and 21 controls, aged between 20 and 40years, were enrolled. Common carotid artery intima-media thickness (CCA-IMT) marker of early atherogenesis, flow-mediated dilatation (FMD) determinants of endothelium-dependent vasodilation, and nitroglycerine-mediated dilatation (NMD) independent marker of vasodilation were measured in two groups. There were no significant differences between the two groups regarding demographic and metabolic characteristics. The mean (±SD) CCA-IMT in methamphetamine users was 0.58±0.09mm, versus 0.59±0.07mm in the controls (p=0.84). Likewise, FMD% was not significantly different between the two groups [7.6±6.1% in methamphetamine users vs. 8.2±5.1% in the controls; p=0.72], nor were peak flow and shear rate after hyperemia. However, NMD% was considerably decreased in the methamphetamine users [8.5±7.8% in methamphetamine users vs. 13.4±6.2% in controls; p=0.03]. According to our results, NMD is reduced among otherwise healthy methamphetamine users, which represents smooth muscle dysfunction in this group. This may contribute to the high risk of stroke among methamphetamine users. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The profile of psychiatric symptoms exacerbated by methamphetamine use.

    PubMed

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

    2016-04-01

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

  2. 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

  3. A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats.

    PubMed

    Miller, Michelle L; Moreno, Amira Y; Aarde, Shawn M; Creehan, Kevin M; Vandewater, Sophia A; Vaillancourt, Brittani D; Wright, M Jerry; Janda, Kim D; Taffe, Michael A

    2013-04-15

    There are no approved pharmacotherapies for d-methamphetamine (METH) addiction and existing therapies have limited efficacy. Advances in using immunotherapeutic approaches for cocaine and nicotine addiction have stimulated interest in creating a similar approach for METH addiction. This study investigated whether active vaccination against METH could potentially attenuate responses to METH in vivo. Male Sprague Dawley rats (n = 32) received a four-boost series with one of three candidate anti-METH vaccines (MH2[R], MH6, and MH7) or a control keyhole limpet hemocyanin conjugate vaccine. Effects of METH on rectal temperature and wheel activity at 27°C ambient temperature were determined. The most efficacious vaccine, MH6, was then contrasted with keyhole limpet hemocyanin conjugate vaccine in a subsequent experiment (n = 16), wherein radiotelemetry determined home cage locomotor activity and body temperature at 23°C ambient temperature. The MH6 vaccine produced high antibody titers with nanomolar affinity for METH and sequestered METH in the periphery of rats. In experiment 1, the thermoregulatory and psychomotor responses produced by METH at 27°C were blocked in the MH6 group. In experiment 2, METH-induced decreases in body temperature and locomotor activity at 23°C were also attenuated in the MH6 group. A pharmacokinetic study in experiment 2 showed that MH6-vaccinated rats had higher METH serum concentrations, yet lower brain METH concentrations, than control rats, and METH concentrations correlated with individual antibody titer. These data demonstrate that active immunopharmacotherapy provides functional protection against physiological and behavioral disruptions induced by METH. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use.

    PubMed

    Heinzerling, Keith G; Swanson, Aimee-Noelle; Hall, Timothy M; Yi, Yi; Wu, Yingnian; Shoptaw, Steven J

    2014-11-01

    Two previous randomized trials found an effect for bupropion in reducing methamphetamine use in the subgroup with lower frequency of methamphetamine use at baseline. This study aimed to replicate these results by comparing bupropion versus placebo in methamphetamine-dependent participants with less than daily methamphetamine use at baseline. Methamphetamine-dependent volunteers reporting methamphetamine use on ≤29 of past 30 days were randomized to bupropion 150 mg twice daily (n = 41) or placebo (n = 43) and out-patient counseling for 12 weeks. The primary outcome was the proportion achieving end-of-treatment (EOT) methamphetamine abstinence (weeks 11 and 12) for bupropion versus placebo. A post-hoc analysis compared EOT abstinence by medication adherence assessed via plasma bupropion/hydroxybupropion level. There was no significant difference in EOT abstinence between bupropion (29%, 12 of 41) and placebo (14%, six of 43; P = 0.087). Among participants receiving bupropion, EOT abstinence was significantly higher in participants assessed as medication adherent by plasma bupropion/hydroxybupropion levels (54%, seven of 13) compared to non-adherent participants (18%, five of 28; P = 0.018). Medication adherence by plasma levels was low (32%). Bupropion may be efficacious for reducing methamphetamine in people with less than daily baseline methamphetamine use, but the evidence remains inconclusive. © 2014 Society for the Study of Addiction.

  5. Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use

    PubMed Central

    Heinzerling, Keith G.; Swanson, Aimee-Noelle; Hall, Timothy M.; Yi, Yi; Wu, Yingnian; Shoptaw, Steven J.

    2014-01-01

    Aims Two previous randomized trials found an effect for bupropion in reducing methamphetamine use in the subgroup with lower frequency of methamphetamine use at baseline. This study aimed to replicate these results by comparing bupropion versus placebo in methamphetamine dependent participants with less than daily methamphetamine use at baseline. Methods Methamphetamine dependent volunteers reporting methamphetamine use on ≤ 29 of past 30 days were randomized to bupropion 150mg twice daily (N=41) or placebo (N=43) and outpatient counseling for 12 weeks. The primary outcome was the proportion achieving end of treatment (EOT) methamphetamine abstinence (weeks 11 and 12) for bupropion versus placebo. A post hoc analysis compared EOT abstinence by medication adherence assessed via plasma bupropion/hydroxybupropion level. Results There was no significant difference in EOT abstinence between bupropion (29%, 12/41) and placebo (14%, 6/43; p = 0.087). Among participants receiving bupropion, EOT abstinence was significantly higher in participants assessed as medication adherent by plasma bupropion/hydroxybupropion levels (54%, 7/13) compared to non-adherent participants (18%, 5/28; p = 0.018). Medication adherence by plasma levels was low (32%). Conclusions Bupropion may be efficacious for methamphetamine dependence but only in a highly selected subgroup of medication adherent participants with less than daily baseline methamphetamine use. Even a single objective “snapshot” measure of medication adherence is highly associated with treatment outcomes. PMID:24894963

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

    PubMed

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

    2017-07-01

    Methamphetamine use is escalating in Australia and New Zealand, with increasing emergency department attendance and mortality. Cardiac complications play a large role in methamphetamine-related mortality, and it would be informative to assess the frequency of abnormal electrocardiograms (ECGs) amongst methamphetamine users. To determine the frequency and severity of ECG abnormalities amongst methamphetamine users compared to a control group. We conducted a retrospective cohort analysis on 212 patients admitted to a tertiary hospital (106 patients with methamphetamine use, 106 age and gender-matched control patients). Electrocardiograms were analysed according to American College of Cardiology guidelines. Mean age was 33.4 years, with 73.6% male gender, with no significant differences between groups in smoking status, ECG indication, or coronary angiography rates. Methamphetamine users were more likely to have psychiatric admissions (22.6% vs 1.9%, p<0.0001). Overall, ECG abnormalities were significantly more common (71.7% vs 32.1%, p<0.0001) in methamphetamine users, particularly tachyarrhythmias (38.7% vs 26.4%, p<0.0001), right axis deviation (7.5% vs 0.0%, p=0.004), left ventricular hypertrophy (26.4% vs 4.7%, p<0.0001), P pulmonale pattern (7.5% vs 0.9%, p=0.017), inferior Q waves (10.4% vs 0.0%, p=0.001), lateral T wave inversion (3.8% vs 0.0%, p=0.043), and longer QTc interval (436.41±31.61ms vs 407.28±24.38ms, p<0.0001). Transthoracic echocardiogram (n=24) demonstrated left ventricular dysfunction (38%), thrombus (8%), valvular lesions (17%), infective endocarditis (17%), and pulmonary hypertension (13%). Electrocardiograms were only moderately sensitive at predicting abnormal TTE. Electrocardiographic abnormalities are more common in methamphetamine users than age and gender-matched controls. Due to the high frequency of abnormalities, ECGs should be performed in all methamphetamine users who present to hospital. Methamphetamine users with abnormal ECGs

  7. Gender difference in early initiation of methamphetamine use among current methamphetamine users in Muse, Northern Shan State, Myanmar.

    PubMed

    Saw, Yu Mon; Saw, Thu Nandar; Yasuoka, Junko; Chan, Nyein; Kham, Nang Pann Ei; Khine, Wint; Cho, Su Myat; Jimba, Masamine

    2017-05-08

    Globally, methamphetamine (MA) use is a significant public health concern due to unprecedented health effects of its use. However, gender similarities and differences in early age of MA initiation and its risk factors among current MA users have been understudied in a developing country setting. A community-based, cross-sectional study was conducted using a computer assisted self-interviewing program from January to March 2013 in Muse, Northern Shan State, Myanmar. A total of 1362 (775 male and 587 female) self-reported current MA users aged between 18 and 35 years were recruited using respondent-driven sampling. Two gender-stratified multiple logistic regression models (models I and II) were done for analysis. For similarities, 73.0% of males and 60.5% of females initiated MA before their 18th birthday. The early age of MA initiation was positively associated with the reasons and places of the first time MA use among both genders. For differences, males [hazard ratio 1.35; 95% confidence interval, 1.18-1.54] had a significantly higher risk than females to initiate MA at earlier age. Among male users, participants who had bisexual/homosexual preferences were more likely to initiate MA use earlier. In contrast, female users who exchanged sex for money and/or drugs were more likely to initiate MA in earlier age. More than 60.0% of male and female participants initiated MA use early; however, males initiated use earlier than females. Although similarities were found among both genders, differences found in key risk factors for early age MA initiation suggest that gender-specific, MA prevention programs are urgently needed in Myanmar.

  8. Depression ratings, reported sexual risk behaviors, and methamphetamine use: latent growth curve models of positive change among gay and bisexual men in an outpatient treatment program.

    PubMed

    Jaffe, Adi; Shoptaw, Steven; Stein, Judith; Reback, Cathy J; Rotheram-Fuller, Erin

    2007-06-01

    Although the cessation of substance use is the principal concern of drug treatment programs, many individuals in treatment experience co-occurring problems such as mood disruptions and sexual risk behaviors that may complicate their recovery process. This study assessed relationships among dynamic changes tracked over time in methamphetamine use, depression symptoms, and sexual risk behaviors (unprotected anal intercourse) in a sample of 145 methamphetamine-dependent gay and bisexual males enrolled in a 16-week outpatient drug treatment research program. Participants were randomly assigned into 1 of 4 conditions: contingency management (CM), cognitive behavioral therapy (CBT; the control condition), combined CM and CBT, and a tailored gay-specific version of the CBT condition. Using latent growth curve models, the authors assessed the relationship of means (intercepts) and the slopes of the 3 measures of interest over time to test whether changes in methamphetamine use predicted declining rates of depression and risky sexual behavior in tandem. Participants with the greatest downward trajectory in methamphetamine use (urine verified) reported the greatest and quickest decreases in reported depressive symptoms and sexual risk behaviors. The control group reported the most methamphetamine use over the 16 weeks; the tailored gay-specific group reported a more rapidly decreasing slope in methamphetamine use than the other participants. Findings indicate that lowering methamphetamine use itself has a concurrent and synergistic effect on depressive symptoms and risky sexual behavior patterns. This suggests that some users who respond well to treatment may show improvement in these co-occurring problems without a need for more intensive targeted interventions.

  9. Methamphetamine and its impact on dental care.

    PubMed

    Klasser, Gary D; Epstein, Joel

    2005-11-01

    Dental professionals should be aware that methamphetamine (MA) use is on the rise in North America. MA is a potent central nervous system stimulant with limited therapeutic effects. The allure of this drug is its availability in many different forms that are relatively easy to make and distribute and inexpensive to purchase and that produce prolonged euphoria for the user. This euphoria results from alteration of the normal physiologic processing of several centrally acting neurotransmitters, which also causes neurotoxicity and neurodegeneration with long-term use. Long-term use of MA has been associated with severe oral health effects, the most notable being a distinctive pattern of caries called methamphetamine-induced caries. Dental professionals need to recognize and understand patients who may be using MA and the risk factors associated with its deleterious oral effects. This knowledge will allow appropriate and effective preventive and treatment strategies for users of this drug.

  10. Patterns of methamphetamine abuse and their consequences.

    PubMed

    Cho, Arthur K; Melega, William P

    2002-01-01

    The abuse of methamphetamine (METH) continues to increase throughout all age groups in different regions of the United States. "Ice," the popularized jargon for (+) methamphetamine hydrochloride, is the predominant drug form that is now consumed. "Ice" is effectively absorbed after either smoking or snorting and it is this rapid influx of drug that produces effects similar to those after intravenous administration. The intensity of METH actions in the central and peripheral nervous system shows tolerance after chronic administration, indicating that neuroadaptations have occurred. Thus, the physiological processes and corresponding biochemical mechanisms that regulate neuronal function have been changed by METH exposure. These biological alterations contribute to the craving and dependence associated with METH abuse and the withdrawal syndrome upon abstinence. However, these changes in behavior may also result from METH-induced neurotoxicity. This article reviews aspects of METH pharmacokinetics and related molecular pharmacodynamics that represent METH pharmacology and then relates those actions to their potential to produce neurotoxicity in humans.

  11. 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

  12. Methamphetamine Ingestion Misdiagnosed as Centruroides sculpturatus Envenomation

    PubMed Central

    Strommen, Joshua; Shirazi, Farshad

    2015-01-01

    The authors present a case report of a 17-month-old female child who ingested a large amount of methamphetamine that looked very similar clinically to a scorpion envenomation specific to the southwestern United States by the species Centruroides sculpturatus. The child was initially treated with 3 vials of antivenom specific for that scorpion species and showed a transient, though clinically relevant neurologic improvement. Her clinical course of sympathomimetic toxicity resumed and she was treated with intravenous fluids and benzodiazepines after blood analysis showed significant levels of d-methamphetamine. This case report is to specifically underline the clinical confusion in discerning between these two conditions and the realization of limited and/or expensive resources that may be used in the process. PMID:25649670

  13. Long-term outcomes in methamphetamine psychosis patients after first hospitalisation.

    PubMed

    Kittirattanapaiboon, Phunnapa; Mahatnirunkul, Suwat; Booncharoen, Hathaichonnee; Thummawomg, Pornthip; Dumrongchai, Unchalee; Chutha, Worawan

    2010-07-01

    As a consequence of the methamphetamine epidemic in Thailand, the occurrence of methamphetamine psychosis (MAP) dramatically increased. This study aimed to examine the long-term outcomes of MAP patients following their first presentation to a psychiatric hospital. Methamphetamine psychosis patients who were first hospitalised in Suan Prung psychiatric hospital Thailand in 2000-2001 were identified through a review of the hospital database. Eligible participants were scheduled for visits by trained field researchers in 2007. For those giving consent, a structured face-to-face interview was conducted. Outcomes were collected from both medical records and interviews. A total of 1116 participants were included in the study. Ninety-two (8.2%) participants had died from suicide, accident or AIDS. Due to relocation, only 449 (40.2%) individuals were interviewed. Most of the participants were male (90.6%) with a mean age of 33.3 years (SD = 8.0). The medical records showed that 263 had revisited the hospital in the interim. Of those, 39.2% were re-hospitalised and 38% were given a diagnosis of schizophrenia due to persistent psychosis. The outreach interview found that more than half (55.7%) had experienced psychosis relapse. Mini International Neuropsychiatric Interview revealed the following current conditions: psychotic disorders (15.8%), alcohol use disorders (52.1%) and suicidality (22.3%). Participants who did not have a diagnosis of current methamphetamine abuse could be divided into those with a single episode psychosis (52.6%) and those with chronic course of psychosis (38.8%). Individuals with MAP are likely to have poor outcomes, in terms of premature death, several relapses of psychotic symptoms, chronic psychotic manifestation, and very rates of alcohol use disorder and suicidality. Therefore, those individuals with MAP require long-term monitoring and psychiatric care.

  14. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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

  16. HIV testing and sero-prevalence among methamphetamine users seeking substance abuse treatment in Cape Town.

    PubMed

    Gouse, Hetta; Joska, John A; Lion, Ryan R; Watt, Melissa H; Burnhams, Warren; Carrico, Adam W; Meade, Christina S

    2016-09-01

    Methamphetamine use is highly prevalent in parts of South Africa, and there is concern this will contribute to the country's substantial HIV epidemic. We examined the feasibility of implementing routine HIV testing at a community-based substance abuse treatment centre in Cape Town and determined the HIV sero-prevalence among methamphetamine users seeking treatment at this site. In this cross-sectional study, 293 participants completed measures of demographics, substance use and HIV treatment. HIV sero-prevalence was determined by a rapid finger-prick HIV test, and prior HIV diagnosis was confirmed via clinic records. The majority of participants were male and self-identified as 'Coloured', with a mean age of 28 years. The HIV sero-prevalence was 3.8%. Of the 11 participants who tested HIV positive, four were newly diagnosed. HIV-positive and HIV-negative participants were comparable on demographic and substance use factors. Uptake of HIV testing among all clients at the drug treatment centre increased from <5% prior to study initiation to 89% after study completion. Measures implemented to ensure high rates of HIV testing were regarded as sustainable. Our study suggests that integrating routine HIV testing into substance abuse treatment is feasible in a community-based health centre. The low HIV prevalence among this sample of treatment-seeking methamphetamine users highlights the potential benefits of supporting expanded efforts to optimise HIV prevention with this young adult population. [Gouse H, Joska JA, Lion RR, Watt MH, Burnhams W, Carrico AW, Meade CS. HIV testing and sero-prevalence among methamphetamine users seeking substance abuse treatment in Cape Town. Drug Alcohol Rev 2016;35:580-583]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  17. Psychiatric disorders in individuals with methamphetamine dependence: prevalence and risk factors.

    PubMed

    Akindipe, Taiwo; Wilson, Don; Stein, Dan J

    2014-06-01

    Methamphetamine dependence may be associated with a range of psychiatric disorders. However, relatively few studies have systematically examined these disorders and possible risk factors. This study used a structured diagnostic interview to assess the prevalence and pattern of co-morbid psychiatric disorders in individuals with methamphetamine dependence; and identified risk factors for this comorbidity. One hundred adult volunteers with a diagnosis of methamphetamine dependence and without co-morbid medical disorders were consecutively recruited from three drug rehabilitation centres. Each volunteer was assessed with a socio-demographic questionnaire and evaluated for psychiatric comorbidity using the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). A regression model was used to determine predictors of psychiatric comorbidity. Co-morbid psychiatric disorders were present in 36.0% of the sample; these included mood disorders (16.0%), psychotic disorders (13.0%) and anxiety disorders (7.0%). One in four of these disorders were assessed as being substance-induced. Independent predictors of psychiatric comorbidity included being male (OR = 10.04, 95% C.I = 2.07-48.63, p = 0.004), younger (OR = 0.87, 95% C.I = 0.77-0.99, p = 0.04), and having a previous psychiatric disorder (OR = 18.45, 95% C.I = 3.81-89.33, p < 0.001). Mood, psychotic, and anxiety disorders are common in individuals with methamphetamine dependence. Risk factors for such comorbidity can be identified. These findings underscore the need for an integrated model of care addressing both substance use disorders and psychiatric comorbidity.

  18. [Prevalence and Therapy of Crystal Methamphetamine Dependence].

    PubMed

    Soyka, Michael; Koller, Gabi; Proebstl, Lisa; Kamp, Felicia; Franke, Andreas; Schmidt, Peggy; Baumgärtner, Gerd; Schacht-Jablonowsky, Maik; Sievert, Annegret; Straif, Maximilian; Hamdorf, Willem

    2017-02-01

    Following a short overview on the epidemiology and clinical correlates of amphetamine abuse and dependence, with special emphasis on metamphetamine ("crystal"), current treatment concepts and recent results of therapy research are discussed. The efficacy of two inpatient treatment models for methamphetamine dependence are currently studied in a study funded by the German Ministry of health. The study concept is given and possible implications are discussed. © Georg Thieme Verlag KG Stuttgart · New York.

  19. 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. © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Alternative reinforcer response cost impacts methamphetamine choice in humans.

    PubMed

    Bennett, J Adam; Stoops, William W; Rush, Craig R

    2013-01-01

    Methamphetamine use disorders are a persistent public health concern. Behavioral treatments have demonstrated that providing access to non-drug alternative reinforcers reduces methamphetamine use. The purpose of this human laboratory experiment was to determine how changes in response cost for non-drug alternative reinforcers influenced methamphetamine choice. Seven subjects with past year histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 8 or 16 mg) and completed a battery of subject-rated and physiological measures. During subsequent sessions, subjects then made eight discrete choices between 1/8th of the sampled dose and an alternative reinforcer ($0.25). The response cost to earn a methamphetamine dose was always 500 responses (FR500). The response cost for the alternative reinforcer varied across sessions (FR500, FR1000, FR2000, FR3000). Methamphetamine functioned as a positive reinforcer and produced prototypical stimulant-like effects (e.g., elevated blood pressure, increased ratings of Stimulated). Choice for doses over money was sensitive to changes in response cost for alternative reinforcers in that more doses were taken at higher FR values than at lower FR values. Placebo choices changed as a function of alternative reinforcer response cost to a greater degree than active methamphetamine choices. These findings suggest that manipulating the effort necessary to earn alternative reinforcers could impact methamphetamine use.

  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. 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…

  5. The rise of methamphetamine in Southeast and East Asia.

    PubMed

    McKetin, Rebecca; Kozel, Nicholas; Douglas, Jeremy; Ali, Robert; Vicknasingam, Balasingam; Lund, Johannes; Li, Jih-Heng

    2008-05-01

    Southeast and East Asia has become a global hub for methamphetamine production and trafficking over the past decade. This paper describes the rise of methamphetamine supply and to what extent use of the drug is occurring in the region. The current review uses data collected through the Drug Abuse Information Network for Asia and the Pacific (DAINAP) and other available sources to analyse retrospectively methamphetamine trends within Southeast and East Asia. Southeast and East Asia has experienced a methamphetamine epidemic in the past decade which began around 1997 and peaked in 2000-2001. While the situation has since stabilised in many countries, methamphetamine trafficking and use are still increasing in parts of the Mekong region and there is evidence of large-scale manufacture in Cambodia, Indonesia, Malaysia and the Philippines. Methamphetamine is typically smoked or ingested, but injection of the drug is apparent. While the peak of the methamphetamine epidemic has passed in parts of Southeast and East Asia, attention is needed to minimise the potential consequences of spreading methamphetamine production, trafficking and use in the Mekong region and in the peninsular and archipelago of Southeast Asia.

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. Alternative Reinforcer Response Cost Impacts Methamphetamine Choice in Humans

    PubMed Central

    Bennett, J. Adam; Stoops, William W.; Rush, Craig R.

    2012-01-01

    Methamphetamine use disorders are a persistent public health concern. Behavioral treatments have demonstrated that providing access to non-drug alternative reinforcers reduces methamphetamine use. The purpose of this human laboratory experiment was to determine how changes in response cost for non-drug alternative reinforcers influenced methamphetamine choice. Seven subjects with past year histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 8 or 16 mg) and completed a battery of subject-rated and physiological measures. During subsequent sessions, subjects then made eight discrete choices between 1/8th of the sampled dose and an alternative reinforcer ($0.25). The response cost to earn a methamphetamine dose was always 500 responses (FR500). The response cost for the alternative reinforcer varied across sessions (FR500, FR1000, FR2000, FR3000). Methamphetamine functioned as a positive reinforcer and produced prototypical stimulant-like effects (e.g., elevated blood pressure, increased ratings of “Stimulated”). Choice for doses over money was sensitive to changes in response cost for alternative reinforcers in that more doses were taken at higher FR values than at lower FR values. Placebo choices changed as a function of alternative reinforcer response cost to a greater degree than active methamphetamine choices. These findings suggest that manipulating the effort necessary to earn alternative reinforcers could impact methamphetamine use. PMID:23046851

  17. 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

  18. The patients in recovery (PIR) perspective: teaching physicians about methamphetamine.

    PubMed

    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 highly, stating it would lead to concrete change in their teaching, research, or patient care practices and they would invite the workshop to their institution for presentation. Direct interaction with PIR was the most valued aspect of the workshop. Lessons learned included patient's fear of being "turned in" limits disclosure of methamphetamine use to physicians; active users have little insight into methamphetamine-related changes in physical appearance; and a sense of productivity reinforces ongoing methamphetamine use. Workshops that include small group discussions between physicians and PIR are an innovative, practical, and acceptable method to teach physicians about their role in helping patients with substance dependence.

  19. Baclofen decreases methamphetamine self-administration in rats.

    PubMed

    Ranaldi, Robert; Poeggel, Kerry

    2002-07-02

    In the present study we tested the hypothesis that baclofen, a GABA-B receptor agonist, attenuates methamphetamine self-administration. Fifteen rats were trained to self-administer i.v. injections of methamphetamine (0, 0.0625, 0.125 and 0.25 mg/kg/injection) on a progressive ratio schedule of reinforcement, and then were tested under the influence of two doses of baclofen (2.5 or 5.0 mg/kg, i.p.). Baclofen significantly reduced break points at all doses of methamphetamine, producing a dose-orderly shift of the methamphetamine dose-response function to the right. These data suggest that pretreatment with baclofen reduces methamphetamine reward. These data are consistent with other studies showing impairment of drug reward after pretreatment with baclofen and add further support to the idea that GABA-B agonists may be useful in the treatment of drug addiction.

  20. Antemortem and postmortem methamphetamine blood concentrations: three case reports.

    PubMed

    McIntyre, Iain M; Nelson, Craig L; Schaber, Bethann; Hamm, Catherine E

    2013-01-01

    We compare antemortem whole-blood to postmortem peripheral blood concentrations of methamphetamine and its metabolite amphetamine in three medical examiner cases. Antemortem specimens, initially screened positive for methamphetamine by ELISA, were subsequently confirmed, together with the postmortem specimens, by GC-MS analysis following solid-phase extraction. Methamphetamine peripheral blood to antemortem blood ratios averaged 1.51 (± 0.049; n = 3) and amphetamine peripheral blood to antemortem blood ratios averaged 1.50 (n = 2). These data show that postmortem redistribution occurs for both methamphetamine and amphetamine, revealing that postmortem blood concentrations are ∼1.5 times greater than antemortem concentrations. Furthermore, as both methamphetamine and amphetamine have previously been shown to have liver/peripheral blood (L/P) ratios of 5-8, it can be proposed that drugs displaying L/P ratios ranging from 5 to 10 may exhibit postmortem concentrations up to twice those concentrations circulating in blood before death.

  1. Pharmacotherapeutic agents in the treatment of methamphetamine dependence.

    PubMed

    Morley, Kirsten C; Cornish, Jennifer L; Faingold, Alon; Wood, Katie; Haber, Paul S

    2017-05-01

    Methamphetamine use is a serious public health concern in many countries and is second to cannabis as the most widely abused illicit drug in the world. Effective management for methamphetamine dependence remains elusive and the large majority of methamphetamine users relapse following treatment. Areas covered: Progression in the understanding of the pharmacological basis of methamphetamine use has provided us with innovative opportunities to develop agents to treat dependence. The current review summarizes relevant literature on the neurobiological and clinical correlates associated with methamphetamine use. We then outline agents that have been explored for potential treatments in preclinical studies, human laboratory phase I and phase II trials over the last ten years. Expert opinion: No agent has demonstrated a broad and strong effect in achieving MA abstinence in Phase II trials. Agents with novel therapeutic targets appear promising. Advancement in MA treatment, including translation into practice, faces several clinical challenges.

  2. Structural brain changes in prenatal methamphetamine-exposed children.

    PubMed

    Roos, Annerine; Jones, Gaby; Howells, Fleur M; Stein, Dan J; Donald, Kirsten A

    2014-06-01

    The global use of methamphetamine (MA) has increased substantially in recent years, but the effect of MA on brain structure in prenatally exposed children is understudied. Here we aimed to investigate potential changes in brain volumes and cortical thickness of children with prenatal MA-exposure compared to unexposed controls. Eighteen 6-year old children with MA-exposure during pregnancy and 18 healthy controls matched for age, gender and socio-economic background underwent structural imaging. Brain volumes and cortical thickness were assessed using Freesurfer and compared using ANOVA. Left putamen volume was significantly increased, and reduced cortical thickness was observed in the left hemisphere of the inferior parietal, parsopercularis and precuneus areas of MA-exposed children compared to controls. Compared to control males, prenatal MA-exposed males had greater volumes in striatal and associated areas, whereas MA-exposed females predominantly had greater cortical thickness compared to control females. In utero exposure to MA results in changes in the striatum of the developing child. In addition, changes within the striatal, frontal, and parietal areas are in part gender dependent.

  3. Capillary microextraction: A new method for sampling methamphetamine vapour.

    PubMed

    Nair, M V; Miskelly, G M

    2016-11-01

    Clandestine laboratories pose a serious health risk to first responders, investigators, decontamination companies, and the public who may be inadvertently exposed to methamphetamine and other chemicals used in its manufacture. Therefore there is an urgent need for reliable methods to detect and measure methamphetamine at such sites. The most common method for determining methamphetamine contamination at former clandestine laboratory sites is selected surface wipe sampling, followed by analysis with gas chromatography-mass spectrometry (GC-MS). We are investigating the use of sampling for methamphetamine vapour to complement such wipe sampling. In this study, we report the use of capillary microextraction (CME) devices for sampling airborne methamphetamine, and compare their sampling efficiency with a previously reported dynamic SPME method. The CME devices consisted of PDMS-coated glass filter strips inside a glass tube. The devices were used to dynamically sample methamphetamine vapour in the range of 0.42-4.2μgm(-3), generated by a custom-built vapour dosing system, for 1-15min, and methamphetamine was analysed using a GC-MS fitted with a ChromatoProbe thermal desorption unit. The devices showed good reproducibility (RSD<15%), and a curvilinear pre-equilibrium relationship between sampling times and peak area, which can be utilised for calibration. Under identical sampling conditions, the CME devices were approximately 30 times more sensitive than the dynamic SPME method. The CME devices could be stored for up to 3days after sampling prior to analysis. Consecutive sampling of methamphetamine and its isotopic substitute, d-9 methamphetamine showed no competitive displacement. This suggests that CME devices, pre-loaded with an internal standard, could be a feasible method for sampling airborne methamphetamine at former clandestine laboratories.

  4. Risk of Cardiovascular Diseases and Stroke Events in Methamphetamine Users: A 10-Year Follow-Up Study.

    PubMed

    Huang, Ming-Chyi; Yang, Shu-Yu; Lin, Shih-Ku; Chen, Kuan-Yu; Chen, Ying-Yeh; Kuo, Chian-Jue; Hung, Yen-Ni

    2016-10-01

    Long-term follow-up data regarding the association between methamphetamine use and cardiovascular and cerebrovascular complications are scarce. We investigated the risk of complications in methamphetamine users over a decade. A total of 1,315 inpatients treated for methamphetamine use were recruited from the Psychiatric Inpatient Medical Claims database in Taiwan between January 1, 1997, and December 31, 2000, and matched with a population proxy comparison group at a ratio of 1:4 through propensity score matching. All patients were monitored for any incident complication until December 31, 2010. Cox proportional hazards model was used to estimate the risk of ICD-9-CM cardiovascular diseases and stroke events. The patients were mostly male, and approximately half were younger than 30 years. The methamphetamine cohort had higher incidences of cardiovascular diseases and stroke events than the comparison cohort (87.5/10,000 vs 55.3/10,000 person-years, P < .001) and was significantly associated with an increased risk of the complications (hazard ratio [HR] = 1.55, P < .001), particularly arrhythmia (HR = 1.92, P = .014) and hemorrhagic stroke (HR = 2.09, P = .001). The risk of cardiovascular sequelae was more significant in younger patients (< 30 y) (HR = 2.22, P = .001), whereas the risk of stroke events was higher among the older patients (≥ 30 y) (HR = 1.86, P = .001). Methamphetamine use is significantly associated with a risk of subsequent cardiovascular and cerebrovascular complications. Age appears to be an effect modifier for the risk estimation.

  5. Extended-release naltrexone for methamphetamine dependence among men who have sex with men: a randomized placebo-controlled trial.

    PubMed

    Coffin, Phillip O; Santos, Glenn-Milo; Hern, Jaclyn; Vittinghoff, Eric; Santos, Deirdre; Matheson, Tim; Colfax, Grant; Batki, Steven L

    2017-07-22

    Methamphetamine use is increasingly prevalent and associated with HIV transmission. Early-phase human studies suggested naltrexone reduced amphetamine use among dependent individuals. We tested if extended-release naltrexone (XRNTX) reduces methamphetamine use and associated sexual risk behaviors among high-risk methamphetamine-dependent men who have sex with men (MSM). Double-blind, placebo-controlled, randomized trial of XRTNX versus placebo over 12 weeks from 2012 to 2015. San Francisco Department of Public Health, California, USA. One hundred community-recruited, sexually-active, actively-using methamphetamine-dependent MSM. Mean age was 43.2 years; 96% were male, 3% transfemale, and 1% transmale; 55.0% were white, 19.0% African American, and 18.0% Latino. XRNTX 380 mg (n = 50) or matched placebo (n = 50) administered by gluteal injection at 4-week intervals. Regression estimated average level and change in level of positive urines during the period 2-12 weeks (primary outcomes) and sexual risk behaviors (secondary outcome). Ninety per cent of visits were completed. By intent-to-treat, participants assigned to XRNTX had similar differences during 2-12 weeks in methamphetamine-positive urines as participants assigned to placebo [incidence rate ratio (IRR) = 0.95, 95% confidence interval (CI) = 0.76-1.20; Bayes factor < 0.3]. Observed urine positivity declined from 78 to 70% in the XRNTX arm and 74 to 64% in the placebo arm. Adherence to injections was 96.7% in the XRNTX arm and 91.3% in the placebo arm. Sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug and no differences in frequency of adverse events by treatment arm. Notwithstanding very high medication adherence for this study, extended-release naltrexone does not appear to reduce methamphetamine use or sexual risk behaviors among methamphetamine-dependent men who have sex with men compared with

  6. Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers.

    PubMed

    Verrico, Christopher D; Mahoney, James J; Thompson-Lake, Daisy G Y; Bennett, Ryan S; Newton, Thomas F; De La Garza, Richard

    2014-02-01

    Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine. Additionally, the effects of treatment with varenicline on the cardiovascular and reinforcing effects of methamphetamine were determined. We conducted a double-blind, placebo-controlled, within-subjects trial of varenicline vs. placebo in methamphetamine-dependent volunteers who were not seeking treatment. Participants were randomly assigned to receive one dose of varenicline (0, 1, or 2 mg) po BID, titrated up to the target dose over days 1-7, during each of three separate inpatient phases. Safety measures included the frequency, duration, severity, and relatedness of adverse events reported. Positive subjective effects included 'Any drug effect', 'High', 'Good effects', 'Stimulated', and 'Drug liking', which were rated by participants before and for 1 h after smoking methamphetamine (0, 10, and 30 mg). There were no serious adverse events and no differences in adverse events reported during the three phases. Varenicline (2 mg) significantly reduced ratings of 'Any drug effect' and 'Stimulated', as well as attenuated ratings of 'High', 'Drug liking', and 'Good effects', produced by methamphetamine (30 mg). The ability of varenicline to attenuate the positive subjective effects of methamphetamine in the laboratory suggests that varenicline should continue to be explored as a treatment for methamphetamine dependence.

  7. Discriminative stimulus and subject-rated effects of methamphetamine, d-amphetamine, methylphenidate, and triazolam in methamphetamine-trained humans.

    PubMed

    Sevak, Rajkumar J; Stoops, William W; Hays, Lon R; Rush, Craig R

    2009-03-01

    Methamphetamine abuse is a significant public health concern. Although widely studied in laboratory animals, little is known about the abuse-related behavioral effects of methamphetamine relative to other abused stimulants in controlled laboratory settings in humans. The aim of this study was to examine the discriminative stimulus, subject-rated, performance, and cardiovascular effects of methamphetamine in humans. In the present study, subjects first learned to discriminate 10 mg of oral methamphetamine from placebo. After acquiring the discrimination (> or = 80% drug-appropriate responding on four consecutive sessions), a range of oral doses of methamphetamine (2.5-15 mg), d-amphetamine (2.5-15 mg), methylphenidate (5-30 mg), and triazolam (0.0625-0.375 mg) was tested. Methamphetamine functioned as a discriminative stimulus and produced prototypical stimulant-like subject-rated effects. d-Amphetamine and methylphenidate produced dose-related increases in methamphetamine-appropriate responding, whereas triazolam did not. d-Amphetamine and methylphenidate produced stimulant-like behavioral effects, whereas triazolam produced sedative-like effects. Methamphetamine, but no other drug, increased heart rate, systolic pressure, and diastolic pressure significantly above placebo levels. Performance in the Digit-Symbol Substitution Test was not affected by any of the drugs tested. Overall, these results demonstrate that the acute behavioral effects of methamphetamine, d-amphetamine, and methylphenidate overlap extensively in humans, which is concordant with findings from preclinical studies. Future studies should assess whether the similarity in the behavioral effects of methamphetamine and related stimulants can be extended to other behavioral assays, such as measures of reinforcement, in humans.

  8. Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers

    PubMed Central

    Verrico, Christopher D.; Mahoney, James J.; Thompson-Lake, Daisy G. Y.; Bennett, Ryan S.; Newton, Thomas F.; De La Garza, Richard

    2015-01-01

    Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine. Additionally, the effects of treatment with varenicline on the cardiovascular and reinforcing effects of methamphetamine were determined. We conducted a double-blind, placebo-controlled, within-subjects trial of varenicline vs. placebo in methamphetamine-dependent volunteers who were not seeking treatment. Participants were randomly assigned to receive one dose of varenicline (0, 1, or 2 mg) po BID, titrated up to the target dose over days 1–7, during each of three separate inpatient phases. Safety measures included the frequency, duration, severity, and relatedness of adverse events reported. Positive subjective effects included ‘Any drug effect’, ‘High’, ‘Good effects’, ‘Stimulated’, and ‘Drug liking’, which were rated by participants before and for 1 h after smoking methamphetamine (0, 10, and 30 mg). There were no serious adverse events and no differences in adverse events reported during the three phases. Varenicline (2 mg) significantly reduced ratings of ‘Any drug effect’ and ‘Stimulated’, as well as attenuated ratings of ‘High’, ‘Drug liking’, and ‘Good effects’, produced by methamphetamine (30 mg). The ability of varenicline to attenuate the positive subjective effects of methamphetamine in the laboratory suggests that varenicline should continue to be explored as a treatment for methamphetamine dependence. PMID:24393456

  9. Brain levels of neuropeptides in human chronic methamphetamine users.

    PubMed

    Frankel, Paul S; Alburges, Mario E; Bush, Lloyd; Hanson, Glen R; Kish, Stephen J

    2007-09-01

    Animal data show that neuropeptide systems in the dopamine-rich brain areas of the striatum (caudate, putamen, and nucleus accumbens) are influenced by exposure to psychostimulants, suggesting that neuropeptides are involved in mediating aspects of behavioral responses to drugs of abuse. To establish in an exploratory study whether levels of neuropeptides are altered in brain of human methamphetamine users, we measured tissue concentrations of dynorphin, metenkephalin, neuropeptide Y, neurotensin, and substance P in autopsied brains of 16 chronic methamphetamine users and 17 matched control subjects. As expected, levels of most neuropeptides were enriched in dopamine-linked brain regions such as the nucleus accumbens and striatum of normal human brain. In contrast to animal findings of increased neuropeptide levels following short-term methamphetamine exposure, striatal neuropeptide concentrations were either normal or moderately decreased in the methamphetamine users. In other examined dopamine-poor cortical and subcortical brain areas, neuropeptide levels were generally either normal or variably reduced. Although the neuropeptide differences might be explained by methamphetamine-induced damage to neuropeptide-containing neurons, our human data are consistent with the possibility that, at least in the human striatum, long-term methamphetamine exposure leads to an adaptive process that is distinct from that which increases neuropeptide levels after acute methamphetamine exposure.

  10. Methamphetamine-induced neural and cognitive changes in rodents.

    PubMed

    Marshall, John F; Belcher, Annabelle M; Feinstein, Erin M; O'Dell, Steven J

    2007-04-01

    Although psychostimulant drug abuse carries with it several potential health risks, the chronic abuse of amphetamines carries the danger of permanent brain injury. The purpose of these experiments is to develop animal models to understand the long-lasting influences of methamphetamine exposure on cerebral cortex and cognitive function. The approach taken is to administer a regimen of methamphetamine known to be neurotoxic to dopamine and serotonin nerve terminals in the rat, and to investigate the influences of that dosing regimen on (i) cortical neuron integrity and function using anatomical stains and (ii) novel object recognition memory. In rodents, repeated administration of methamphetamine during a single day produces long-lasting damage to striatal dopamine and forebrain serotonin terminals as well as degeneration of somatosensory cortical neurons. The degeneration of somatosensory cortical neurons may represent only the most visible form of long-term deleterious effects on cerebral cortex, as exposure of rats to methamphetamine can reduce the immediate early gene responses of neurons in widespread cortical areas, even long after exposure to the drug. Together with the death and long-lasting functional impairments of cortical neurons, rats exposed to methamphetamine have impaired cognitive function. When tested for object recognition memory, methamphetamine-treated rats show deficiencies lasting for at least 3 weeks after drug exposure. Using a rodent model, these findings provide an avenue to study the cortical influences of methamphetamine and their cognitive sequelae.

  11. Assessment of therapeutic potential of amantadine in methamphetamine induced neurotoxicity.

    PubMed

    Thrash-Williams, Bessy; Ahuja, Manuj; Karuppagounder, Senthilkumar S; Uthayathas, Subramaniam; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

    2013-10-01

    Methamphetamine epidemic has a broad impact on world's health care system. Its abusive potential and neurotoxic effects remain a challenge for the anti-addiction therapies. In addition to oxidative stress, mitochondrial dysfunction and apoptosis, excitotoxicity is also involved in methamphetamine induced neurotoxicity. The N-methyl-D-aspartate (NMDA) type of glutamate receptor is thought to be one of the predominant mediators of excitotoxicity. There is growing evidence that NMDA receptor antagonists could be one of the therapeutic options to manage excitotoxicity. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was found to possess NMDA antagonistic properties and has shown to release dopamine from the nerve terminals. The current study aimed to evaluate the effect of amantadine pre-treatment against methamphetamine induced neurotoxicity. Results showed that methamphetamine treatment had depleted striatal dopamine, generated of reactive oxygen species and decreased activity of complex I in the mitochondria. Interestingly, amantadine, at high dose (10 mg/kg), did not prevent dopamine depletion moreover it exacerbated the behavioral manifestations of methamphetamine toxicity such as akinesia and catalepsy. Only lower dose of amantadine (1 mg/kg) produced significant scavenging of the reactive oxygen species induced by methamphetamine. Overall results from the present study suggest that amantadine should not be used concomitantly with methamphetamine as it may results in excessive neurotoxicity.

  12. 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.

  13. The risk of psychotic symptoms associated with recreational methamphetamine use.

    PubMed

    McKetin, Rebecca; Hickey, Karina; Devlin, Kristina; Lawrence, Kerri

    2010-07-01

    To determine whether recreational methamphetamine use is associated with an increased risk of psychotic symptoms. A cross-sectional survey of 157 people attending dance events in Sydney, Australia. Participants were assessed for psychotic symptoms in the past year using items from the Psychosis Screen. Participants with and without psychotic symptoms were compared on methamphetamine use, polydrug use and other demographic factors. An ordinal logistic regression was used to determine the probability of psychotic symptoms by methamphetamine use and level of polydrug use. Psychotic symptoms in the past year were predicted by methamphetamine use and heavier polydrug use in the past year, and a history of a psychotic disorder (schizophrenia, schizoaffective or bipolar affective disorder). After removing participants with a history of a psychotic disorder (n = 16) and adjusting for polydrug use, methamphetamine use increased the probability of two or more psychotic symptoms (indicative of psychosis risk) from 9% to 21%. There was a non-significant increase in the risk of psychotic symptoms with higher levels of polydrug use. Methamphetamine use was typically monthly or less often (83%), and most users described their use as recreational (85%). Within the context of polydrug use, recreational methamphetamine use is associated with a twofold to threefold increase in the probability of psychotic symptoms.

  14. Reduced amygdala and hippocampal volumes in patients with methamphetamine psychosis.

    PubMed

    Orikabe, Lina; Yamasue, Hidenori; Inoue, Hideyuki; Takayanagi, Yoichiro; Mozue, Yuriko; Sudo, Yasuhiko; Ishii, Tatsuji; Itokawa, Masanari; Suzuki, Michio; Kurachi, Masayoshi; Okazaki, Yuji; Kasai, Kiyoto

    2011-11-01

    The similarity between psychotic symptoms in patients with schizophrenia such as hallucinations and delusions and those caused by administration of methamphetamine has been accepted. While the etiology of schizophrenia remains unclear, methamphetamine induced psychosis, which is obviously occurred by methamphetamine administration, had been widely considered as a human pharmaceutical model of exogenous psychosis. Although volume reductions in medial temporal lobe structure in patients with schizophrenia have repeatedly been reported, those in patients with methamphetamine psychosis have not yet been clarified. Magnetic resonance images (MRI) were obtained from 20 patients with methamphetamine psychosis and 20 age, sex, parental socio-economic background, and IQ matched healthy controls. A reliable manual tracing methodology was employed to measure the gray matter volume of the amygdala and the hippocampus from MRIs. Significant gray matter volume reductions of both the amygdala and hippocampus were found bilaterally in the subjects with methamphetamine psychosis compared with the controls. The degree of volume reduction was significantly greater in the amygdala than in hippocampus. While the total gray, white matter and intracranial volumes were also significantly smaller-than-normal in the patients; the regional gray matter volume reductions in these medial temporal structures remained statistically significant even after these global brain volumes being controlled. The prominent volume reduction in amygdala rather than that in hippocampus could be relatively specific characteristics of methamphetamine psychosis, since previous studies have shown significant volume reductions less frequently in amygdala than in hippocampus of the other psychosis such as schizophrenia.

  15. How profitable is methamphetamine dealing in Australia?

    PubMed

    Gong, Wendy; Ritter, Alison; Bright, David; Doran, Chris

    2012-05-01

    The illicit drug trade is the largest in value among global illicit commodities, at some $320 billion US dollars, according to the UN World Drug Report. Endeavours to control such a large illicit market would be enhanced by improved understanding of the economics of the trade. However, due to its illicit nature many aspects of the illicit drug market are largely unknown. This study explored one economic aspect of illicit drug dealing, profitability, with the aim of developing a better picture of the financial gains from illicit drug dealing. Data were obtained from judges sentencing remarks, key informants from law enforcement, and other published reports which detail the prices paid for methamphetamine in Australia. The financial margins attained from non-crystal methamphetamine dealing in Australia were calculated by examining the best fit for the relationship between prices and quantities: in this case a power law. If it is assumed that a single deal is divided ("cut") between 4 times and 20 times before selling to the next customer, the mark-ups can range from 24% to 59%. The mark-ups appear low compared with those found in US research, but similar to those found in UK research. To our knowledge, this is the first attempt to analyse profitability of methamphetamine dealing in Australia. The findings of this study will help in understanding the motivations and decisions of drug dealers, and potentially assist drug law enforcement agencies to design better strategies to dismantle supply chain linkages which generate excessive profits. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Prefrontal glutamate correlates of methamphetamine sensitization and preference

    PubMed Central

    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.

    2016-01-01

    Methamphetamine (MA) is a widely abused, highly addictive, psychostimulant that elicits pronounced deficits in neurocognitive function related to hypo-functioning of the prefrontal cortex (PFC). Our understanding of how repeated methamphetamine impacts excitatory glutamatergic transmission within the PFC is limited, as is information about the relation between PFC glutamate and addiction vulnerability/resiliency. In vivo microdialysis and immunoblotting studies characterized the effects of methamphetamine (10 injections of 2 mg/kg, IP) 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 versus low MA-drinking selectively bred mouse lines (MAHDR versus MALDR, respectively) and inbred C57BL/6J mice exhibiting spontaneously divergent place-conditioning phenotypes. Repeated methamphetamine sensitized drug-induced glutamate release and lowered indices of NMDA receptor expression in C57BL/6J mice, but did not alter basal extracellular glutamate content or total protein expression of Homer proteins, or metabotropic or AMPA glutamate receptors. Elevated basal glutamate, blunted methamphetamine-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 versus low methamphetamine drinking, and Homer2a/b levels were inversely correlated with the motivational valence of methamphetamine in C57BL/6J mice. These data provide novel evidence that repeated, low-dose, methamphetamine 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 methamphetamine addiction vulnerability/resiliency. PMID:26742098

  17. 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.

  18. Perseverative behavior in rats with methamphetamine-induced neurotoxicity.

    PubMed

    Son, Jong-Hyun; Kuhn, James; Keefe, Kristen A

    2013-04-01

    Methamphetamine induces monoamine depletions thought to contribute to cognitive and behavioral dysfunctions. Previously, we reported that methamphetamine-induced neurotoxicity is associated with impaired formation of stimulus-response associations. Additionally, subjective observations suggested that behavioral flexibility might be affected. Thus, the present study examined whether methamphetamine neurotoxicity induces perseverative behavior. Rats were pretreated with (±)-methamphetamine (4 × 10 mg/kg, 2-hr intervals) or saline. Three weeks later, rats were trained to press a lever on one side of an operant chamber and then retrieve the reinforcer from a magazine on the opposite side until they reached criterion (>50 reinforcers/30-min). After four consecutive sessions performing the task at criterion, rats were sacrificed and brains removed for monoamine determinations. Methamphetamine-pretreated rats had ∼50% loss of striatal dopamine and prefrontal serotonin. Methamphetamine- and saline-pretreated rats were not different in the number of sessions required to reach criterion or in the total numbers of lever presses and/or head entries made across the four consecutive sessions at criterion-level performance. However, methamphetamine-pretreated rats earned fewer reinforcers, because they made extra lever-presses and head entries when they should have been retrieving the reinforcer or returning to the lever. Latencies for methamphetamine-pretreated rats to switch between the two behaviors also were significantly slower than latencies for controls. Interestingly, the degree of additional lever-presses negatively correlated with serotonin-transporter binding in the prefrontal cortex, even in saline-pretreated controls. These data suggest that methamphetamine-induced partial monoamine toxicity is associated with perseveration and that the degree of perseveration may depend on serotonin innervation of the frontal cortex. Copyright © 2012 Elsevier Ltd. All rights

  19. 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.

  20. 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

  1. Recurrent corneal ulcerations associated with smokeable methamphetamine abuse.

    PubMed

    Chuck, R S; Williams, J M; Goldberg, M A; Lubniewski, A J

    1996-05-01

    We studied a case of chronic, recurrent, bilateral, corneal ulcerations associated with smokeable methamphetamine abuse, commonly known as "ice," in an otherwise healthy 31-year-old woman. Every few months the patient had recurrent corneal ulcerations. Each time, she was hospitalized and treated successfully with topical antibiotics. Even though she had undergone numerous formal attempts at drug rehabilitation, she continued to have relapses, and ulceration recurred only during periods of smokeable methamphetamine abuse. Illicit use of smokeable methamphetamine may result in corneal ulceration.

  2. The insults of illicit drug use on male fertility.

    PubMed

    Fronczak, Carolyn M; Kim, Edward D; Barqawi, Al B

    2012-01-01

    One-third of infertile couples may have a male factor present. Illicit drug use can be an important cause of male factor infertility and includes use of anabolic-androgenic steroids, marijuana, opioid narcotics, cocaine, and methamphetamines. The use of these illicit drugs is common in the United States, with a yearly prevalence rate for any drug consistently higher in males compared with females. We aim to provide a review of recent literature on the prevalence and effects of illicit drug use on male fertility and to aid health professionals when counseling infertile men whose social history suggests illicit drug use. Anabolic-androgenic steroids, marijuana, cocaine, methamphetamines, and opioid narcotics all negatively impact male fertility, and adverse effects have been reported on the hypothalamic-pituitary-testicular axis, sperm function, and testicular structure. The use of illicit drugs is prevalent in our society and likely adversely impacting the fertility of men who abuse drugs.

  3. Evaluation of modafinil effects on cardiovascular, subjective, and reinforcing effects of methamphetamine in methamphetamine-dependent volunteers.

    PubMed

    De La Garza, Richard; Zorick, Todd; London, Edythe D; Newton, Thomas F

    2010-01-15

    Methamphetamine is a highly addictive stimulant and long-term exposure leads to reductions in dopamine. One therapeutic strategy is to develop and test compounds that normalize dopamine. The primary aim of this study was to determine the safety of modafinil treatment during methamphetamine exposure in a controlled clinical setting. Methamphetamine-dependent volunteers (N=13), who were not seeking treatment, were randomized to receive either modafinil (200mg, PO) or matching placebo over three days (Days 1-3 or Days 8-10). On Day 1, subjects were randomized to modafinil or placebo in the morning, and then 3 and 6h later received infusions of methamphetamine (0 and 30 mg, i.v.), after which cardiovascular and subjective effects were assessed. On Day 3, participants completed i.v. self-administration sessions during which they made 10 choices for low doses of methamphetamine (3mg, i.v.) or saline. Days 4-7 were used as a washout period. On Day 8 participants were assigned to the alternate study medication (placebo or modafinil), and the same testing procedures were repeated through Day 10. The data reveal that modafinil treatment was well-tolerated and not associated with increased incidence of adverse events. In general, modafinil reduced by approximately 25% ratings of methamphetamine-induced "Any Drug Effect", "High", and "Want Methamphetamine", and reduced total number of choices for methamphetamine and monetary value of methamphetamine, though none of these measures reached statistical significance. Given these encouraging, though non-significant trends, the primary conclusion is that it appears safe to proceed with modafinil in further clinical evaluations of therapeutic efficacy. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. Is the self-report of recent cocaine or methamphetamine use reliable in illicit stimulant drug users who present to the Emergency Department with chest pain?

    PubMed

    Lee, Moon O; Vivier, Patrick M; Diercks, Deborah B

    2009-08-01

    Use of illicit drugs results in an increased risk of morbidity and mortality, which is often seen in the Emergency Department (ED). Chest pain is frequently associated with cocaine and methamphetamine use. To determine if the self-report of recent cocaine or methamphetamine use is reliable in illicit stimulant drug users who present to the ED with chest pain. A retrospective review of patients presenting to the ED from July 1, 2004 through June 30, 2006 was undertaken. Inclusion criteria were: age >or= 18 years, chief complaint of chest pain, documented social history of drug abuse, positive urine toxicology screen and myoglobin and troponin levels measured, sent from the ED. For the 318 patients who met the inclusion criteria, the self-report rate of cocaine or methamphetamine use was 51.8% (95% confidence interval [CI] 0.46-0.57). No difference was found in the self-report rate between users of methamphetamine vs. cocaine (odds ratio [OR] 1.12, 95% CI 0.7-1.7). There also was no difference in the self-report rate by patient age < 50 years compared to patient age >or= 50 years (OR 0.67, 95% CI 0.42-1.08). The self-report rate for males compared to females was not significantly different (OR 0.87, 95% CI 0.54-1.4). Patients who had a positive troponin were not significantly more likely to self-report drug use than patients who did not have a positive troponin (OR 1.1, 95% CI 0.55-2.2). The self-report rate among cocaine- or methamphetamine-using patients presenting to the ED with chest pain was 51.8%. There seems to be no significant difference in the self-report rate among those who use methamphetamine vs. those who use cocaine, nor by gender, nor stratified by age over 50 years.

  6. Relationship between gender and psychotic symptoms in cocaine-dependent and methamphetamine-dependent participants.

    PubMed

    Mahoney, James J; Hawkins, Rollin Y; De La Garza, Richard; Kalechstein, Ari D; Newton, Thomas F

    2010-10-01

    women with regard to age, ethnicity, years of use, route of administration, or amount used in the past week. In the "while abstinent" condition, women were significantly more likely than men to report feeling that something was wrong with the way a part of their body looked (72% vs 32%, respectively; P = 0.009), olfactory hallucinations (39% vs 8%; P = 0.010) and dressing inappropriately (22% vs 0%; P = 0.010). During the "while high" condition, women were more likely than men to report delusions of grandeur (33% vs 16%, respectively; P = 0.030), paranoia (50% vs 16%; P = 0.017), and tactile hallucinations (61% vs 32%; P = 0.050). The findings of the present study revealed that cocaine- and methamphetamine-dependent women were more likely than their male counterparts to report experiencing various psychotic symptoms. This information may be useful for clinicians and mental health professionals, who should take these symptoms into account as potential barriers that may impede effective treatment. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

  7. 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

  8. Monitoring the prevalence of methamphetamine-related presentations at psychiatric hospitals in Cape Town, South Africa.

    PubMed

    Plüddemann, A; Dada, S; Parry, C D H; Kader, R; Parker, J S; Temmingh, H; van Heerden, S; de Clercq, C; Lewis, I

    2013-01-01

    This study aimed to determine a demographic profile of methamphetamine (MA)-related admissions to major psychiatric services in Cape Town, obtain a substance use profile from admitted patients, a profile of common MA-related symptoms encountered during the assessment of the patients presenting with MA-related problems, and a brief profile of the psychiatric diagnoses made. Staff in six psychiatric hospitals or wards in Cape Town collected data on methamphetamine related admissions between July and December 2008 using a one-page record review form. The data collection form consisted of the patient's demographic details, presenting symptoms, previous admission details, current MA and other substance use information, and DSM-IV diagnosis. A total of 235 forms were completed. Most patients were male (69%) and the mean age was 25 years. The most common presenting symptoms were aggressive behaviour (74%), followed by delusions (59%) and hallucinations (57%). Males were two times more likely to present with aggression as compared to females, while females were significantly more likely to present with depressed mood or euphoric/elevated mood. The majority of patients had substance-induced psychotic disorder (41%), followed by schizophrenia (31%). Twelve percent (12%) had bipolar mood disorder. MA-related psychiatric admissions pose serious challenges to all health services dealing with these patients. Further training and treatment protocol development and distribution is indicated.

  9. What You Need to Know about Drugs: Methamphetamines

    MedlinePlus

    ... the body and brain, especially with repeated use. Long-term use of methamphetamines can cause brain damage that causes problems with memory and body movement, mood swings, and violent behavior. ...

  10. Remediation of Methamphetamine in Clandestine Laboratories. A Literature Review

    EPA Science Inventory

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

  11. Methamphetamine use and methicillin-resistant Staphylococcus aureus skin infections.

    PubMed

    Cohen, Adam L; Shuler, Carrie; McAllister, Sigrid; Fosheim, Gregory E; Brown, Michael G; Abercrombie, Debra; Anderson, Karen; McDougal, Linda K; Drenzek, Cherie; Arnold, Katie; Jernigan, Daniel; Gorwitz, Rachel

    2007-11-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections and methamphetamine use are emerging public health problems. We conducted a case-control investigation to determine risk factors for MRSA skin and soft tissue infections (SSTIs) in residents of a largely rural southeastern community in the United States. Case-patients were persons >12 years old who had culturable SSTIs; controls had no SSTIs. Of 119 SSTIs identified, 81 (68.1%) were caused by MRSA. Methamphetamine use was reported in 9.9% of case-patients and 1.8% of controls. After we adjusted for age, sex, and race, patients with MRSA SSTIs were more likely than controls to have recently used methamphetamine (odds ratio 5.10, 95% confidence interval 1.55-16.79). MRSA caused most SSTIs in this population. Transmission of MRSA may be occurring among methamphetamine users in this community.

  12. Methamphetamine Use and Methicillin-Resistant Staphylococcus aureus Skin Infections

    PubMed Central

    Shuler, Carrie; McAllister, Sigrid; Fosheim, Gregory E.; Brown, Michael G.; Abercrombie, Debra; Anderson, Karen; McDougal, Linda K.; Drenzek, Cherie; Arnold, Katie; Jernigan, Daniel; Gorwitz, Rachel

    2007-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections and methamphetamine use are emerging public health problems. We conducted a case–control investigation to determine risk factors for MRSA skin and soft tissue infections (SSTIs) in residents of a largely rural southeastern community in the United States. Case-patients were persons >12 years old who had culturable SSTIs; controls had no SSTIs. Of 119 SSTIs identified, 81 (68.1%) were caused by MRSA. Methamphetamine use was reported in 9.9% of case-patients and 1.8% of controls. After we adjusted for age, sex, and race, patients with MRSA SSTIs were more likely than controls to have recently used methamphetamine (odds ratio 5.10, 95% confidence interval 1.55–16.79). MRSA caused most SSTIs in this population. Transmission of MRSA may be occurring among methamphetamine users in this community. PMID:18217555

  13. Remediation of Manufactured Methamphetamine in Clandestine Laboratories. A Literature Review

    EPA Science Inventory

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

  14. 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

  15. Lobeline effects on tonic and methamphetamine-induced dopamine release

    PubMed Central

    Wilhelm, Clare J.; Johnson, Robert A.; Eshleman, Amy J.; Janowsky, Aaron

    2008-01-01

    The mechanisms of interaction between lobeline and the dopamine transporter (DAT) or the vesicular monoamine transporter (VMAT-2) are not clear. The goal of this study was to elucidate the effects of lobeline on these transporters in a cell system co-expressing the DAT and VMAT-2. Lobeline caused release of [3H]dopamine to a similar extent as reserpine (VMAT-2 inhibitor), but was less efficacious than methamphetamine or dopamine. Additionally, lobeline decreased the [3H]dopamine releasing effects of methamphetamine, unlike reserpine which increased release by methamphetamine. These results suggest that lobeline has unique properties at the DAT and VMAT-2 which may make it useful as a pharmacotherapeutic to treat methamphetamine abuse. PMID:18191815

  16. Crystal methamphetamine smoking among regular ecstasy users in Australia: increases in use and associations with harm.

    PubMed

    Kinner, Stuart A; Degenhardt, Louisa

    2008-05-01

    This study examined (a) changes in crystal methamphetamine use among regular ecstasy users (REU) in Australia and (b) associations of crystal use and smoking with demographics, drug use and harm. Cross-sectional surveys (2000-06) of REU in three Australian capital cities, and in 2006, 750 REU in all Australian capital cities. The interview included: demographics, drug use, risk behaviour, recent criminal activity and methamphetamine dependence using Severity of Dependence Scale. There was little change in overall methamphetamine use, but a marked increase in crystal methamphetamine smoking. Among recent methamphetamine users in 2006 (n = 606), crystal methamphetamine users (n = 364) reported more frequent methamphetamine use and higher levels of dependence. Compared with those who had used only other forms of methamphetamine, recent crystal methamphetamine users were more likely to 'binge' on drugs for > or = 48 hours, engage in crime and experience financial and legal problems related to drug use. Non-smoking crystal methamphetamine users (n = 78) more often reported recent injecting and heroin use. Recent smokers were more likely to have: greater polydrug use, recently overdosed on a 'party drug', and accessed medical services for their drug use. Many of these associations were accounted for by their injecting and heavier methamphetamine use, rather than smoking per se. Crystal methamphetamine smoking among REU has increased markedly and is associated with significant harm. This appears related to smokers' heavier levels of methamphetamine use. Effective harm reduction strategies should be tailored to these specific risks.

  17. The Impact of Age, HIV Serostatus and Seroconversion on Methamphetamine Use

    PubMed Central

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

    2016-01-01

    Background Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. Objectives Study aims were to investigate whether 1) methamphetamine use differs by age and HIV serostatus and 2) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. Methods This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. Results Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (β = −.16, p = .01) and a fewer number of days (β = −.18, p = .004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e., grams per day used) was greater among the younger, relative to the older, HIV+ group (p = .02), and increased for both age groups following seroconversion (p < .001). Conclusion These analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum. PMID:26837461

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

    PubMed

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

    2016-03-01

    Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. Study aims were to investigate whether (i) methamphetamine use differs by age and HIV serostatus, and (ii) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (β = -0.16, p = 0.01) and a fewer number of days (β = -0.18, p = 0.004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e. grams per day used) was greater among the younger, relative to the older, HIV+ group (p = 0.02), and increased for both age groups following seroconversion (p < 0.001). These analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum.

  19. Neural correlates of affect processing and aggression in methamphetamine dependence.

    PubMed

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

    2011-03-01

    Methamphetamine abuse is associated with high rates of aggression but few studies have addressed the contributing neurobiological factors. To quantify aggression, investigate function in the amygdala and prefrontal cortex, and assess relationships between brain function and behavior in methamphetamine-dependent individuals. In a case-control study, aggression and brain activation were compared between methamphetamine-dependent and control participants. Participants were recruited from the general community to an academic research center. 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. 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. 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 the bilateral ventral inferior frontal gyrus. During affect labeling, participants recruited the 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 correlated inversely with self-reported aggression in control participants

  20. Is cognitive functioning impaired in methamphetamine users? A critical review.

    PubMed

    Hart, Carl L; Marvin, Caroline B; Silver, Rae; Smith, Edward E

    2012-02-01

    The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy.

  1. Prospective memory impairment in former users of methamphetamine.

    PubMed

    Rendell, Peter G; Mazur, Magdalena; Henry, Julie D

    2009-04-01

    Considerable research indicates that methamphetamine use is associated with neurocognitive impairment, but no empirical study to date has assessed whether these difficulties extend to memory for future intentions (prospective memory). The present study assessed prospective performance on a laboratory measure of prospective memory that closely represents the types of prospective memory tasks that actually occur in everyday life and provides an opportunity to investigate the different sorts of prospective memory failures that occur ("Virtual Week"). Twenty adults with confirmed history of methamphetamine use and dependence, currently engaged in rehabilitation and confirmed to be abstinent for an average period of 6 months, and 20 methamphetamine-naive participants were tested on Virtual Week. Various other aspects of cognitive function were also assessed, including retrospective memory and executive functioning. Methamphetamine users were significantly impaired on Virtual Week, and these deficits did not vary as a function of specific prospective memory task demands. Of all the cognitive measures, cognitive inhibition shared greatest variance with group effects on the prospective memory measure. Prospective memory performance is sensitive to prior methamphetamine use even well into abstinence. Methamphetamine users experience generalized difficulties with prospective memory, suggesting that these deficits are likely to have important implications for day-to-day functioning.

  2. Support for selection of a methamphetamine cleanup standard in Colorado.

    PubMed

    Hammon, Tracy L; Griffin, Susan

    2007-06-01

    Methamphetamine production for illicit use occurs in makeshift labs and is associated with the release of numerous chemicals, including methamphetamine residues. These methamphetamine residues may pose a health risk to residents who reoccupy these structures after property seizures. Several states have established technology-based cleanup standards for methamphetamine, but none have examined the health-protectiveness of these standards. In response to Colorado House Bill 04-1182, exposure intakes correlated with three technology-based standards were calculated for various groups of individuals. Intakes were assessed for a 1-year-old infant, 6-year-old child, and a female of childbearing age. Exposure intakes were compared to toxicity reference values developed from developmental endpoints following methamphetamine exposure from the available literature. Uncertainty factors were applied to the lowest adverse effect levels observed in these studies to arrive at the toxicity reference values. These reference values were greater than the calculated intakes from each proposed technology standard, suggesting that all of the proposed standards would be protective of human health exposure. The cost and practicality of attaining each of the proposed standards was also factored into the decision making process. In their final regulation (6 CCR 1014-3), the CDPHE selected 0.5 microg/100 cm(2) as the final cleanup standard for methamphetamine residues.

  3. Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review

    PubMed Central

    Hart, Carl L; Marvin, Caroline B; Silver, Rae; Smith, Edward E

    2012-01-01

    The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy. PMID:22089317

  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. The sigma receptor agonist SA4503 both attenuates and enhances the effects of methamphetamine

    PubMed Central

    Rodvelt, Kelli R.; Oelrichs, Clark E.; Blount, Lucas R.; Fan, Kuo-Hsien; Lever, Susan Z.; Lever, John R.; Miller, Dennis K.

    2011-01-01

    Background Methamphetamine’s behavioral effects have been attributed to its interaction with monoamine transporters; however, methamphetamine also has affinity for sigma receptors. Method The present study investigated the effect of the sigma receptor agonist SA 4503 and the sigma receptor antagonists BD-1047 and BD-1063 on methamphetamine-evoked [3H] dopamine release from preloaded rat striatal slices. The effect of SA 4503 on methamphetamine-induced hyperactivity and on the discriminative stimulus properties of methamphetamine also was determined. Results SA 4503 attenuated methamphetamine-evoked [3H]dopamine release in a concentration-dependent manner. BD-1047 and BD-1063 did not affect release. SA 4503 dose-dependently potentiated and attenuated methamphetamine-induced hyperactivity. SA 4503 pretreatment augmented the stimulus properties of methamphetamine. Conclusions Our findings indicate that SA 4503 both enhances and inhibits methamphetamine’s effects and that sigma receptors are involved in the neurochemical, locomotor stimulatory and discriminative stimulus properties of methamphetamine. PMID:21277708

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and the methamphetamine they contain is being used as a substitute for amphetamine tablets... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers...

  7. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and the methamphetamine they contain is being used as a substitute for amphetamine tablets... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers...

  8. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and the methamphetamine they contain is being used as a substitute for amphetamine tablets... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers...

  9. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and the methamphetamine they contain is being used as a substitute for amphetamine tablets... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers...

  10. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and the methamphetamine they contain is being used as a substitute for amphetamine tablets... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers...

  11. Posttraumatic stress disorder symptoms, emotion dysregulation, and aggressive behavior among incarcerated methamphetamine users.

    PubMed

    Wahlstrom, Laura C; Scott, Jillian Panuzio; Tuliao, Antover P; DiLillo, David; McChargue, Dennis E

    2015-01-01

    Methamphetamine use remains a prevalent problem in the United States and is linked to numerous deleterious outcomes, including aggressive behavior, criminal activity, and incarceration. Given these associations, a greater understanding of factors that contribute to aggression among users of methamphetamine is needed, particularly within criminal justice settings, where users of this drug are overrepresented. The presen