Science.gov

Sample records for methamphetamine dependent subjects

  1. 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.

  2. 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

  3. 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

  4. Comparison of striatal dopamine transporter levels in chronic heroin-dependent and methamphetamine-dependent subjects.

    PubMed

    Yuan, Jie; Liu, Xing Dang; Han, Mei; Lv, Rong Bin; Wang, Yuan Kai; Zhang, Guang Ming; Li, Yu

    2017-01-01

    To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by (99m) Tc-TRODAT-1 single-photon emission computed tomography (SPECT) brain images in people with heroin and METH dependence. We recruited 21 healthy human controls, 23 heroin-dependent subjects and 25 METH abusers. The heroin- and METH-dependent subjects exhibited negative urine toxicology after undergoing physiological detoxification. All subjects underwent SPECT brain imaging, and specific tracer uptake ratios (SURs) were assessed bilaterally in the regions of interest. A significant SUR reduction in heroin-dependent subjects and METH-dependent subjects compared with healthy controls was found in the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. There were no significant differences in the heroin group and METH group for the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. The scores of craving, HAMA (Hamilton Anxiety Rating Scale), in heroin abusers were lower than in the METH abusers. Our results show that people with heroin and METH dependence who are currently abstinent had lower DAT levels in the striatum than healthy controls. There were no differences in striatal DAT in heroin and METH users. These results suggest that chronic heroin and METH abuse appears to produce similar effects in striatal DAT in humans. METH users may have more serious craving and anxiety symptoms than heroin users with prolonged abstinence.

  5. 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.

  6. 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

  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

    MedlinePlus

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

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

    PubMed Central

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

    2010-01-01

    Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo-controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at α4β2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over one week to reach 1 mg twice daily, and then was co-administered with 30 mg methamphetamine, delivered in 10 intravenous (iv) infusions of 3 mg each. Varenicline was found to be safe in combination with iv methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence.

  10. PREDICTING ADHERENCE TO TREATMENT FOR METHAMPHETAMINE DEPENDENCE FROM NEUROPSYCHOLOGICAL AND DRUG USE VARIABLES*

    PubMed Central

    Dean, Andy C.; London, Edythe D.; Sugar, Catherine A.; Kitchen, Christina M. R.; Swanson, Aimee-Noelle; Heinzerling, Keith G.; Kalechstein, Ari D.; Shoptaw, Steven

    2009-01-01

    Although some individuals who abuse methamphetamine have considerable cognitive deficits, no prior studies have examined whether neurocognitive functioning is associated with outcome of treatment for methamphetamine dependence. In an outpatient clinical trial of bupropion combined with cognitive behavioral therapy and contingency management (Shoptaw et al., 2008), 60 methamphetamine-dependent adults completed three tests of reaction time and working memory at baseline. Other variables that were collected at baseline included measures of drug use, mood/psychiatric functioning, employment, social context, legal status, and medical status. We evaluated the relative predictive value of all baseline measures for treatment outcome using Classification and Regression Trees (CART; Breiman, 1984), a nonparametric statistical technique that produces easily interpretable decision rules for classifying subjects that are particularly useful in clinical settings. Outcome measures were whether or not a participant completed the trial and whether or not most urine tests showed abstinence from methamphetamine abuse. Urine-verified methamphetamine abuse at the beginning of the study was the strongest predictor of treatment outcome; two psychosocial measures (e.g., nicotine dependence and Global Assessment of Functioning) also offered some predictive value. A few reaction time and working memory variables were related to treatment outcome, but these cognitive measures did not significantly aid prediction after adjusting for methamphetamine usage at the beginning of the study. On the basis of these findings, we recommend that research groups seeking to identify new predictors of treatment outcome compare the predictors to methamphetamine usage variables to assure that unique predictive power is attained. PMID:19608354

  11. Investigating the relationship between subjective drug craving and temporal dynamics of the default mode network, executive control network, and salience network in methamphetamine dependents using rsfMRI

    NASA Astrophysics Data System (ADS)

    Soltanian-Zadeh, Somayyeh; Hossein-Zadeh, Gholam-Ali; Shahbabaie, Alireza; Ekhtiari, Hamed

    2016-03-01

    Resting state functional connectivity (rsFC) studies using fMRI provides a great deal of knowledge on the spatiotemporal organization of the brain. The relationships between and within a number of resting state functional networks, namely the default mode network (DMN), salience network (SN) and executive control network (ECN) have been intensely studied in basic and clinical cognitive neuroscience [1]. However, the presumption of spatial and temporal stationarity has mostly restricted the assessment of rsFC [1]. In this study, sliding window correlation analysis and k-means clustering were exploited to examine the temporal dynamics of rsFC of these three networks in 24 abstinent methamphetamine dependents. Afterwards, using canonical correlation analysis (CCA) the possible relationship between the level of self-reported craving and the temporal dynamics was examined. Results indicate that the rsFC transits between 6 discrete "FC states" in the meth dependents. CCA results show that higher levels of craving are associated with higher probability of transiting from state 4 to 6 (positive FC of DMN-ECN getting weak and negative FC of DMN-SN appearing) and staying in state 4 (positive FC of DMN-ECN), lower probability of staying in state 2 (negative FC of DMN-ECN), transiting from state 4 to 2 (change of positive FC of DMN-ECN to negative FC), and transiting from state 3 to 5 (appearance of negative FC of DMN-SN and positive FC of DMN-ECN with the presence of negative FC of SN-ECN). Quantitative measures of temporal dynamics in large-scale brain networks could bring new added values to increase potentials for applications of rsfMRI in addiction medicine.

  12. Methamphetamine

    MedlinePlus

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

  13. Acute buspirone dosing enhances abuse-related subjective effects of oral methamphetamine.

    PubMed

    Pike, Erika; Stoops, William W; Rush, Craig R

    There is not an approved pharmacotherapy for treating methamphetamine use disorder. This study sought to determine the effects of acute buspirone treatment on the subjective and cardiovascular effects of oral methamphetamine in order to provide an initial assessment of the utility, safety, and tolerability of buspirone for managing methamphetamine use disorder. We predicted that acute buspirone administration would reduce the subjective effects of methamphetamine. We also predicted that the combination of buspirone and methamphetamine would be safe and well tolerated. Ten subjects completed the protocol, which tested three methamphetamine doses (0, 15, and 30mg) in combination with two buspirone doses (0 and 30mg) across 6 experimental sessions. Subjective effects and physiological measures were collected at regular intervals prior to and after dose administration. Methamphetamine produced prototypical subjective and cardiovascular effects. Acute buspirone administration increased some of the abuse-related subjective effects of methamphetamine and also attenuated some cardiovascular effects. The combination of oral methamphetamine and buspirone was safe and well tolerated. Acute buspirone administration may increase the abuse liability of oral methamphetamine. Chronic buspirone dosing studies remain to be conducted, but given preclinical findings and the outcomes of this work, the utility of buspirone for treating methamphetamine use disorder appears limited.

  14. Modafinil administration improves working memory in methamphetamine-dependent individuals who demonstrate baseline impairment.

    PubMed

    Kalechstein, Ari D; De La Garza, Richard; Newton, Thomas F

    2010-01-01

    Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects. This double-blind, placebo-controlled study evaluated whether a daily dose of 400 mg of modafinil, administered over three consecutive days, would enhance performance on a measure of working memory relative to test performance at baseline and following 3 days of placebo administration in 11 methamphetamine addicted, nontreatment-seeking volunteers. The results revealed that participants demonstrating relatively poor performance on the third day of a 3-day washout period (ie, at baseline), showed significant improvement on measures of working memory, but not on measures of episodic memory or information processing speed. In contrast, for participants demonstrating relatively high performance at baseline, modafinil administration did not affect test scores. The findings provide an initial indication that modafinil can reverse methamphetamine-associated impairments in working memory.

  15. Effect of add-on valproate on craving in methamphetamine depended patients: A randomized trial

    PubMed Central

    Kheirabadi, Gholam Reza; Ghavami, Masoud; Maracy, Mohammad Reza; Salehi, Mehrdad; Sharbafchi, Mohammad Reza

    2016-01-01

    Background: Methamphetamine dependence lead to the compulsive use, loss of control, and social and occupational dysfunctions. This study aimed to compare the effect of valproate in reducing the craving in methamphetamine dependents. Materials and Methods: This is a randomized, double-blind, controlled clinical trial on 40 men of 18–40 years old referred to Noor Hospital during December 2012–September 2013 in Isfahan, Iran. The subjects participated in matrix program and randomly were divided into two groups of valproate and placebo. A 4-months program of intervention with valproate or placebo was arranged for each group. The rate of craving to methamphetamine and positive methamphetamine urine tests were evaluated in both groups every 2 weeks using cocaine craving questionnaire-brief (CCQ-Brief) and urine test. After the 4 months (active treatment with valproate and placebo), the drug was tapered and discontinued within 10 days, and patients were introduced to self-help groups and monitored regularly on a weekly basis over another 3 months. Collected data were analyzed with SPSS 20 using analysis of covariance repeated measure, Chi-square, and t-test. Results: CCQ score of the intervention group was significantly less than the placebo group (P < 0.001), except on weeks 1, 3, and 28. The ratio of a positive urine test for methamphetamine in the intervention group was significantly lower than the control group in all screenings except weeks 3 and 28. Conclusion: Adding valproate to matrix program in the treatment of methamphetamine dependence showed significant effect on the reduction of the craving to methamphetamine. PMID:27656618

  16. 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

  17. Rivastigmine reduces "Likely to use methamphetamine" in methamphetamine-dependent volunteers.

    PubMed

    De La Garza, R; Newton, T F; Haile, C N; Yoon, J H; Nerumalla, C S; Mahoney, J J; Aziziyeh, A

    2012-04-27

    We previously reported that treatment with the cholinesterase inhibitor rivastigmine (3mg, PO for 5days) significantly attenuated "Desire for METH". Given that higher dosages of rivastigmine produce greater increases in synaptic ACh, we predicted that 6mg should have more pronounced effects on craving and other subjective measures. In the current study, we sought to characterize the effects of short-term exposure to rivastigmine (0, 3 or 6mg) on the subjective and reinforcing effects produced by administration of methamphetamine (METH) in non-treatment-seeking, METH-dependent volunteers. This was a double-blind, placebo-controlled, crossover study. Participants received METH on day 1, and were then randomized to placebo or rivastigmine on day 2 in the morning and treatment continued through day 8. METH dosing was repeated on day 6. The data indicate that METH (15 and 30mg), but not saline, increased several positive subjective effects, including "Any Drug Effect", "High", "Stimulated", "Desire METH", and "Likely to Use METH" (all p's<0.0001). In addition, during self-administration sessions, participants were significantly more likely to choose METH over saline (p<0.0001). Evaluating outcomes as peak effects, there was a trend for rivastigmine to reduce "Desire METH" (p=0.27), and rivastigmine significantly attenuated "Likely to Use METH" (p=0.01). These effects were most prominent for rivastigmine 6mg when participants were exposed to the low dose (15mg, IV), but not high dose (30mg, IV), of METH. The self-administration data reveal that rivastigmine did not alter total choices for METH (5mg, IV/choice). Overall, the results indicate some efficacy for rivastigmine in attenuating key subjective effects produced by METH, though additional research using higher doses and longer treatment periods is likely needed. These data extend previous findings and indicate that cholinesterase inhibitors, and other drugs that target acetylcholine systems, warrant continued

  18. 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 ...

  19. Prosthodontics treatment considerations for methamphetamine-dependent patients.

    PubMed

    Gantos, Meredith A; Manzotti, Anna; Yuan, Judy Chia-Chun; Afshari, Fatemeh S; Marinis, Aristotelis; Syros, George; Rynn, Michelle Howard; Sukotjo, Cortino

    2015-01-01

    Overt dental disease is a distinguishing comorbidity associated with methamphetamine abuse, necessitating the need for special management to maximize treatment benefits. As this highly addictive stimulant increases in popularity, it has become imperative that clinicians are equipped to thoughtfully provide comprehensive care for these patients. This article reviews the impact of methamphetamine to systemic and oral health and proposes a comprehensive treatment plan and sequence for the methamphetamine-dependent patient. A multidisciplinary approach is recommended. Destructive oral and psychological changes must be identified and controlled. A thorough risk assessment, caries control, and preventative plan should be established before initiating prosthodontic treatment. Patient motivation, support, and a timely recall schedule are integral for dental longevity.

  20. HIV and chronic methamphetamine dependence affect cerebral blood flow.

    PubMed

    Ances, Beau M; Vaida, Florin; Cherner, Mariana; Yeh, Melinda J; Liang, Christine L; Gardner, Carly; Grant, Igor; Ellis, Ronald J; Buxton, Richard B

    2011-09-01

    Human immunodeficiency virus (HIV) and methamphetamine (METH) dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV-/METH-, eight HIV-/METH+, 24 HIV+/METH-, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH dependence. HIV+ individuals had a trend towards a lower baseline CBF (-10%, p = 0.07) and greater CBF changes for the functional task (+32%, p = 0.01) than HIV- subjects. Individuals with a previous history of METH dependence had a lower baseline CBF (-16%, p = 0.007) and greater CBF changes for a functional task (+33%, p = 0.02). However, no interaction existed between HIV serostatus and previous history of METH dependence for either baseline CBF (p = 0.53) or CBF changes for a functional task (p = 0.10). In addition, CBF and volume in the LN were not correlated. A possible additive relationship could exist between HIV infection and a history of METH dependence on CBF with a previous history of METH dependence having a larger contribution. Abnormalities in CBF could serve as a surrogate measure for assessing the chronic effects of HIV and previous METH dependence on brain function.

  1. Extinction of drug cue reactivity in methamphetamine-dependent individuals.

    PubMed

    Price, Kimber L; Saladin, Michael E; Baker, Nathaniel L; Tolliver, Bryan K; DeSantis, Stacia M; McRae-Clark, Aimee L; Brady, Kathleen T

    2010-09-01

    Conditioned responses to drug-related environmental cues (such as craving) play a critical role in relapse to drug use. Animal models demonstrate that repeated exposure to drug-associated cues in the absence of drug administration leads to the extinction of conditioned responses, but the few existing clinical trials focused on extinction of conditioned responses to drug-related cues in drug-dependent individuals show equivocal results. The current study examined drug-related cue reactivity and response extinction in a laboratory setting in methamphetamine-dependent individuals. Methamphetamine cue-elicited craving was extinguished during two sessions of repeated (3) within-session exposures to multi-modal (picture, video, and in-vivo) cues, with no evidence of spontaneous recovery between sessions. A trend was noted for a greater attenuation of response in participants with longer (4-7 day) inter-session intervals. These results indicate that extinction of drug cue conditioned responding occurs in methamphetamine-dependent individuals, offering promise for the development of extinction- based treatment strategies.

  2. Typologies of positive psychotic symptoms in methamphetamine dependence

    PubMed Central

    Bousman, Chad A.; McKetin, Rebecca; Burns, Richard; Woods, Steven Paul; Morgan, Erin E.; Atkinson, J. Hampton; Everall, Ian P.; Grant, Igor

    2014-01-01

    Background and Objectives Understanding methamphetamine associated psychotic (MAP) symptom typologies could aid in identifying individuals at risk of progressing to schizophrenia and guide early intervention. Methods Latent class analysis (LCA) of psychotic symptoms collected from 40 methamphetamine dependent individuals with a history of psychotic symptoms but no history of a primary psychotic disorder. Results Three typologies were identified. In one, persecutory delusions dominated (Type 1), in another persecutory delusions were accompanied by hallucinations (Type 2), and in the third a high frequency of all the assessed hallucinatory and delusional symptoms was observed (Type 3). Discussion and Conclusion MAP is a heterogeneous syndrome with positive symptom typologies. Scientific Significance This study represents the first attempt at identifying typologies of MAP and highlights the potential utility of LCA in future large-scale studies. PMID:25864598

  3. 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.

  4. 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

  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. 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.

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

    PubMed

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

    2016-01-01

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

  8. Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine.

    PubMed

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

    2016-06-01

    Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of D-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and "positive" subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone.Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6 to 7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected.Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like "positive" subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10-mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.

  9. 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

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

    PubMed

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

    2011-03-01

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

  11. Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults.

    PubMed

    Cherner, Mariana; Suarez, Paola; Casey, Corinna; Deiss, Robert; Letendre, Scott; Marcotte, Thomas; Vaida, Florin; Atkinson, J Hampton; Grant, Igor; Heaton, Robert K

    2010-01-15

    Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH-) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n=32) and impaired (n=22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine.

  12. 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.

  13. Differential effects of donepezil on methamphetamine and cocaine dependencies.

    PubMed

    Takamatsu, Yukio; Yamanishi, Yoshiharu; Hagino, Yoko; Yamamoto, Hideko; Ikeda, Kazutaka

    2006-08-01

    Donepezil, a choline esterase inhibitor, has been widely used as a medicine for Alzheimer's disease. Recently, a study showed that donepezil inhibited addictive behaviors induced by cocaine, including cocaine-conditioned place preference (CPP) and locomotor sensitization to cocaine. In the present study, we investigated the effects of donepezil on methamphetamine (METH)-induced behavioral changes in mice. In counterbalanced CPP tests, the intraperitoneal (i.p.) administration of 3 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit METH CPP, whereas pretreatment with 3 mg/kg donepezil abolished the CPP for cocaine (10 mg/kg, i.p.). Similarly, in locomotor sensitization experiments, i.p. administration of 1 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit locomotor sensitivity to METH, whereas pretreatment with 1 mg/kg donepezil significantly inhibited locomotor sensitivity to cocaine (10 mg/kg, i.p.). These results suggest that donepezil may be a useful tool for treating cocaine dependence but not for treating METH dependence. The differences in the donepezil effects on addictive behaviors induced by METH and cocaine might be due to differences in the involvement of acetylcholine in the mechanisms of METH and cocaine dependencies.

  14. The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers.

    PubMed

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

    2011-04-01

    Impulsivity and craving have been independently hypothesized to contribute to sustained drug use and relapse in addiction. The primary focus of this project was to determine the relationship between impulsivity and craving in 85 cocaine-dependent and 73 methamphetamine-dependent, non-treatment-seeking volunteers. Drug use was assessed with a 14-item, self-report drug and alcohol use questionnaire. Self report instruments utilized included the Barratt Impulsivity Scale (BIS) and the Visual Analog Scale (VAS), which probed "just before your last use of cocaine (for cocaine-dependent participants) or methamphetamine (for methamphetamine-dependent participants), how much craving did you experience?" The groups were similar with respect to recent use of cocaine or methamphetamine, alcohol, nicotine, and marijuana. Analysis of variance (ANOVA) did not reveal significant differences between cocaine and methamphetamine groups for total impulsivity or total craving. Simple linear regression revealed correlations between total impulsivity and total craving in cocaine (r(2)=0.05, p≤0.03) and methamphetamine users (r(2)=0.09, p≤0.008). Participants were separated into high impulsivity (HIBIS) or low impulsivity (LOBIS) subgroups using a median split. ANOVA revealed significantly higher craving in the HIBIS group versus the LOBIS group in methamphetamine users (p≤0.02), but not in cocaine users. For both cocaine and methamphetamine groups, level of impulsivity and craving were found to be related to some drug use variables including years of alcohol use, severity of withdrawal, and craving level following drug use. Taken together, this study shows a marginal relationship between impulsivity and craving, which may further the understanding of motivational factors contributing to ongoing drug use and addiction in psychostimulant users.

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

    PubMed

    Saika, Fumihiro; Kiguchi, Norikazu; Kishioka, Shiroh

    2015-10-01

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

  16. Frontal white matter changes and aggression in methamphetamine dependence.

    PubMed

    Lederer, Katharina; Fouche, Jean-Paul; Wilson, Don; Stein, Dan J; Uhlmann, Anne

    2016-02-01

    Chronic methamphetamine (MA) use can lead to white matter (WM) changes and increased levels of aggression. While previous studies have examined WM abnormalities relating to cognitive impairment, associations between WM integrity and aggression in MA dependence remain unclear. Diffusion Tensor Imaging (DTI) was used to investigate WM changes in 40 individuals with MA dependence and 40 matched healthy controls. A region of interest (ROI) approach using tract based spatial statistics (TBSS) in FSL was performed. We compared fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ║) and perpendicular diffusivity (λ┴) in WM tracts of the frontal brain. A relationship of WM with aggression scores from the Buss & Perry Questionnaire was investigated. Mean scores for anger (p < 0.001), physical aggression (p = 0.032) and total aggression (p = 0.021) were significantly higher in the MA group relative to controls. ROI analysis showed increased MD (U = 439.5, p = 0.001) and λ┴ (U = 561.5, p = 0.021) values in the genu of the corpus callosum, and increased MD (U = 541.5, p = 0.012) values in the right cingulum in MA dependence. None of the WM changes were significantly associated with aggression scores. This study provides evidence of frontal WM changes and increased levels of aggression in individuals with MA dependence. The lack of significant associations between WM and aggressive behaviour may reflect methodological issues in measuring such behaviour, or may indicate that the neurobiology of aggression is not simply correlated with WM damage but is more complex.

  17. Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

    PubMed Central

    White, Sarah; Laurenzana, Elizabeth; Hendrickson, Howard; Gentry, W. Brooks

    2011-01-01

    We tested the hypothesis that differences in (+)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t1/2λz) of METH and (+)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t1/2λz was 37% longer than METH t1/2λz (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t1/2λz was significantly shorter than metabolite AMP t1/2λz (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death. PMID:21632964

  18. Gestation time-dependent pharmacokinetics of intravenous (+)-methamphetamine in rats.

    PubMed

    White, Sarah; Laurenzana, Elizabeth; Hendrickson, Howard; Gentry, W Brooks; Owens, S Michael

    2011-09-01

    We tested the hypothesis that differences in (+)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t(1/2λz)) of METH and (+)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t(1/2λz) was 37% longer than METH t(1/2λz) (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t(1/2λz) was significantly shorter than metabolite AMP t(1/2λz) (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death.

  19. 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

  20. Childhood Adverse Events and Health Outcomes among Methamphetamine-Dependent Men and Women

    ERIC Educational Resources Information Center

    Messina, Nena P.; Marinelli-Casey, Patricia; Hillhouse, Maureen; Ang, Alfonso; Hunter, Jeremy; Rawson, Richard

    2008-01-01

    To describe the prevalence of childhood adverse events (CAEs) among methamphetamine-dependent men and women, and assess the relationship of cumulative CAEs to health problems. Data for 236 men and 351 women were analyzed assessing CAEs. Dependent variables included 14 self-reported health problems or psychiatric symptom domains. Mental health was…

  1. The Effects of Methylphenidate on Cognitive Control in Active Methamphetamine Dependence Using Functional Magnetic Resonance Imaging

    PubMed Central

    Jan, Reem K.; Lin, Joanne C.; McLaren, Donald G.; Kirk, Ian J.; Kydd, Rob R.; Russell, Bruce R.

    2014-01-01

    Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18–46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive

  2. "Frontal systems" behaviors in comorbid human immunodeficiency virus infection and methamphetamine dependency.

    PubMed

    Marquine, María J; Iudicello, Jennifer E; Morgan, Erin E; Brown, Gregory G; Letendre, Scott L; Ellis, Ronald J; Deutsch, Reena; Woods, Steven Paul; Grant, Igor; Heaton, Robert K

    2014-01-30

    Human immunodeficiency virus (HIV) infection and methamphetamine (MA) dependence are associated with neural injury preferentially involving frontostriatal circuits. Little is known, however, about how these commonly comorbid conditions impact behavioral presentations typically associated with frontal systems dysfunction. Our sample comprised 47 HIV-uninfected/MA-nondependent; 25 HIV-uninfected/MA-dependent; 36 HIV-infected/MA-nondependent; and 28 HIV-infected/MA-dependent subjects. Participants completed self-report measures of "frontal systems" behaviors, including impulsivity/disinhibition, sensation-seeking, and apathy. They also underwent comprehensive neurocognitive and neuropsychiatric assessments that allowed for detailed characterization of neurocognitive deficits and comorbid/premorbid conditions, including lifetime Mood and Substance Use Disorders, Attention-Deficit/Hyperactivity Disorder, and Antisocial Personality Disorder. Multivariable regression models adjusting for potential confounds (i.e., demographics and comorbid/premorbid conditions) showed that MA dependence was independently associated with increased impulsivity/disinhibition, sensation-seeking and apathy, and HIV infection with greater apathy. However, we did not see synergistic/additive effects of HIV and MA on frontal systems behaviors. Global neurocognitive impairment was relatively independent of the frontal systems behaviors, which is consistent with the view that these constructs may have relatively separable biopsychosocial underpinnings. Future research should explore whether both neurocognitive impairment and frontal systems behaviors may independently contribute to everyday functioning outcomes relevant to HIV and MA.

  3. 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.

  4. 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

  5. Does alexithymia explain variation in cue-elicited craving reported by methamphetamine-dependent individuals?

    PubMed

    Saladin, Michael E; Santa Ana, Elizabeth J; LaRowe, Steven D; Simpson, Annie N; Tolliver, Bryan K; Price, Kimber L; McRae-Clark, Aimee L; Brady, Kathleen T

    2012-01-01

    Drug craving is an important motivational phenomenon among addicted individuals, and successful management of craving is essential to both the initiation and maintenance of abstinence. Although craving in response to drug cues is common in drug-dependent individuals, it is not universal. At the present time, it is not known why approximately 20-30% of all addicted persons fail to report appreciable craving in laboratory-based cue reactivity studies. This study examined the possibility that alexithymia, a personality attribute characterized by a difficulty identifying and describing emotions, may contribute to the impoverished cue-elicited craving experienced by some addicts. Specifically, we tested the hypothesis that alexithymia, as measured by the Toronto Alexithymia Scale (TAS), would be inversely related to the magnitude of cue-elicited craving obtained in a cue reactivity protocol. Forty methamphetamine-dependent individuals completed the TAS and provided craving ratings for methamphetamine after presentation of methamphetamine-associated cues. Thirteen participants (32%) reported no methamphetamine cue-elicited craving. Contrary to expectation, TAS factor 1 (a measure of difficulty identifying feelings) scores were positively associated with cue-elicited craving. Thus, the results suggest that increasing difficulty-identifying feelings may be associated with higher cue-elicited craving. Clinical implications for this finding are discussed.

  6. Effect of the environmental enrichment on the severity of psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats.

    PubMed

    Hajheidari, Samira; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2015-01-01

    Previously results have been shown that chronic methamphetamine causes dependence, withdrawal syndrome and drug craving. Also, environmental enrichment (EE) has been shown protective effects in several animal models of addiction. This study evaluated effect of the EE on the anxiety-depression profile and voluntary METH consumption in METH-dependent rats after abstinence. The rats were chronically treated with bi-daily doses (2 mg/kg, at 12 h intervals) of METH over a period of 14 days. METH dependent rats reared in standard environment (SE) or EE during spontaneous METH withdrawal which lasted 30 days. Then, the rats were tested for anxiety (the elevated plus maze-EPM) and depression (forced swim test-FST) and also voluntary consumption of METH using a two-bottle choice paradigm (TBC). The results showed that the EE rats exhibited an increase in EPM open arm time and entries (P < 0.05), lower levels of immobility (P < 0.001) as compared with the SE groups. Preference ratio of METH was less in the METH/EE rats than the SE group during 2 periods of the intake of drug (P < 0.05). Environmental enrichment seems to be one of the strategies in reduction of behavioral deficits and the risk of relapse induced by METH withdrawal.

  7. Elevated Aspartate and Alanine Aminotransferase Levels and Natural Death among Patients with Methamphetamine Dependence

    PubMed Central

    Kuo, Chian-Jue; Tsai, Shang-Ying; Liao, Ya-Tang; Conwell, Yeates; Lee, Wen-Chung; Huang, Ming-Chyi; Lin, Shih-Ku; Chen, Chiao-Chicy; Chen, Wei J.

    2012-01-01

    Background Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methods Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex- and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. Results In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p<0.001) in the group with markedly elevated AST (>80 U/L) and 2.66 (p<0.05) in the group with mildly elevated AST (40–80 U/L), with reference to the control group (<40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p<0.001), and 1.44 (p>0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. Conclusions This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural

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

    PubMed Central

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

    2012-01-01

    Methamphetamine (METH) dependence is frequently comorbid with HIV infection and both have been linked to alterations of brain structure and function. In a previous study, we showed that the brain volume loss characteristic of HIV infection contrasts with METH-related volume increases in striatum and parietal cortex, suggesting distinct neurobiological responses to HIV and METH (Jernigan et al., 2005). fMRI has the potential to reveal functional interactions between the effects of HIV and METH. In the present study, 50 participants were studied in four groups: an HIV+ group, a recently METH dependent group, a dually affected group, and a group of unaffected community comparison subjects. An fMRI paradigm consisting of motor sequencing tasks of varying levels of complexity was administered to examine blood oxygenation level dependent (BOLD) changes. Within all groups, activity increased significantly with increasing task complexity in large clusters within sensorimotor and parietal cortex, basal ganglia, cerebellum, and cingulate. The task complexity effect was regressed on HIV status, METH status, and the HIVxMETH interaction term in a simultaneous multiple regression. HIV was associated with less complexity-related activation in striatum, whereas METH was associated with less complexity-related activation in parietal regions. Significant interaction effects were observed in both cortical and subcortical regions; and, contrary to expectations, the complexity-related activation was less aberrant in dually-affected than in single-risk participants, in spite of comparable levels of neurocognitive impairment among the clinical groups. Thus, HIV and METH dependence, perhaps through their effects on dopaminergic systems, may have opposing functional effects on neural circuits involved in motor programming. PMID:22608157

  9. 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

  10. Influence of Betaxolol on the Methamphetamine Dependence in Mice

    PubMed Central

    Kim, Byoung-Jo; Park, Jong-Il; Eun, Hun-Jeong

    2016-01-01

    Objective The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. Methods The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. Results The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. Conclusion These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP. PMID:27247598

  11. 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.

  12. Dopamine transporter dysfunction in Han Chinese people with chronic methamphetamine dependence after a short-term abstinence.

    PubMed

    Yuan, Jie; Lv, Rongbin; Robert Brašić, James; Han, Mei; Liu, Xingdang; Wang, Yuankai; Zhang, Guangming; Liu, Congjin; Li, Yu; Deng, Yanping

    2014-01-30

    Single-photon emission-computed tomography (SPECT) after the administration of (99m)Tc-TRODAT-1 was performed on healthy subjects and subjects with methamphetamine (METH)dependence at time 1 (T1) after 24-48 h of abstinence, time 2 (T2) after 2 weeks of abstinence, and time 3 (T3) after 4 weeks of abstinence. In contrast to values in controls, the values of the striatal DAT specific uptake ratios (SURs) in subjects with METH dependence were significantly lower at T1 (n=25), T2 (n=9), and T3 (n=8); a mild increase in SURs was observed at T2 and T3, but values were still significantly lower than those in controls. In subjects with METH dependence, there was a trend for a negative correlation of striatal DAT SURs and craving for METH at T1. METH craving, anxiety and depression scores significantly decreased from T1 to T2 to T3. We conclude that Han Chinese people with METH dependence experience significant striatal DAT dysfunction, and that these changes may be mildly reversible after 4 weeks of abstinence, but that DAT levels still remain significantly lower than those in healthy subjects. The mild recovery of striatal DAT may parallel improvements in craving, anxiety and depression.

  13. 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. ...

  14. Time-dependent effects of prazosin on the development of methamphetamine conditioned hyperactivity and context-specific sensitization in mice.

    PubMed

    White, André O; Rauhut, Anthony S

    2014-04-15

    The present experiments examined the effects of prazosin, a selective α₁-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 min prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 h (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-h delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α₁-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes.

  15. Striatum and Insula Dysfunction during Reinforcement Learning Differentiates Abstinent and Relapsed Methamphetamine Dependent Individuals

    PubMed Central

    Stewart, Jennifer L.; Connolly, Colm G.; May, April C.; Tapert, Susan F.; Wittmann, Marc; Paulus, Martin P.

    2013-01-01

    Background and aims Individuals with methamphetamine dependence (MD) exhibit dysfunction in brain regions involved in goal maintenance and reward processing when compared with healthy individuals. We examined whether these characteristics also reflect relapse vulnerability within a sample of MD patients. Design Longitudinal, with functional magnetic resonance imaging (fMRI) and clinical interview data collected at baseline and relapse status collected at one-year follow up interview. Setting Keck Imaging Center, University of California San Diego, USA Participants MD patients (n=60) enrolled in an inpatient drug treatment program at baseline. MD participants remaining abstinent at one year follow-up (Abstinent MD group; n=42) were compared with MD participants who relapsed within this period (Relapsed MD group; n=18). Measurements Behavioral and neural responses to a reinforcement learning (Paper-Scissors-Rock) paradigm recorded during an fMRI session at time of treatment. Findings The Relapsed MD group exhibited greater bilateral inferior frontal gyrus (IFG) and right striatal activation than the Abstinent MD group during the learning of reward contingencies (Cohen’s d range: 0.60–0.83). In contrast, the Relapsed MD group displayed lower bilateral striatum, bilateral insula, left IFG, and left anterior cingulate activation than the Abstinent MD group (Cohen’s d range: 0.90–1.23) in response to winning, tying, and losing feedback. Conclusions Methamphetamine-dependent individuals who achieve abstinence and then relapse show greater inferior frontal gyrus activation during learning, and relatively attenuated striatal, insular, and frontal activation in response to feedback, compared with methamphetamine-dependent people who remain abstinent. PMID:24329936

  16. Childhood maltreatment and amygdala connectivity in methamphetamine dependence: a pilot study

    PubMed Central

    Dean, Andy C; Kohno, Milky; Hellemann, Gerhard; London, Edythe D

    2014-01-01

    Introduction Childhood maltreatment, a well-known risk factor for the development of substance abuse disorders, is associated with functional and structural abnormalities in the adult brain, particularly in the limbic system. However, almost no research has examined the relationship between childhood maltreatment and brain function in individuals with drug abuse disorders. Methods We conducted a pilot study of the relationship between childhood maltreatment (evaluated with the Childhood Trauma Questionnaire; Bernstein and Fink 1998) and resting-state functional connectivity of the amygdala (bilateral region of interest) with functional magnetic resonance imaging in 15 abstinent, methamphetamine-dependent research participants. Within regions that showed connectivity with the amygdala as a function of maltreatment, we also evaluated whether amygdala connectivity was associated positively with negative affect and negatively with healthy emotional processing. Results The results indicated that childhood maltreatment was positively associated with resting-state connectivity between the amygdala and right hippocampus, right parahippocampal gyrus, right inferior temporal gyrus, right orbitofrontal cortex, cerebellum, and brainstem. Furthermore, connectivity between the amygdala and hippocampus was positively related to measures of depression, trait anxiety, and emotion dysregulation, and negatively related to self-compassion and dispositional mindfulness. Conclusions These findings suggest that childhood maltreatment may contribute to increased limbic connectivity and maladaptive emotional processing in methamphetamine-dependent adults, and that healthy emotion regulation strategies may serve as a therapeutic target to ameliorate the associated behavioral phenotype. Childhood maltreatment warrants further investigation as a potentially important etiological factor in the neurobiology and treatment of substance use disorders. PMID:25365801

  17. The impact of clinical and demographic variables on cognitive performance in methamphetamine-dependent individuals in rural South Carolina.

    PubMed

    Price, Kimber L; DeSantis, Stacia M; Simpson, Annie N; Tolliver, Bryan K; McRae-Clark, Aimee L; Saladin, Michael E; Baker, Nathaniel L; Wagner, Mark T; Brady, Kathleen T

    2011-01-01

    Inconsistencies in reports on methamphetamine (METH) associated cognitive dysfunction may be attributed, at least in part, to the diversity of study sample features (eg, clinical and demographic characteristics). The current study assessed cognitive function in a METH-dependent population from rural South Carolina, and the impact of demographic and clinical characteristics on performance. Seventy-one male (28.2%) and female (71.8%) METH-dependent subjects were administered a battery of neurocognitive tests including the Test of Memory Malingering (TOMM), Shipley Institute of Living Scale, Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Grooved Pegboard Test, California Verbal Learning Test (CVLT), and Wisconsin Card Sorting Test (WCST). Demographic and clinical characteristics (eg, gender, frequency of METH use) were examined as predictors of performance. Subjects scored significantly lower than expected on one test of attention and one of fine motor function, but performed adequately on all other tests. There were no predictors of performance on attention; however, more frequent METH use was associated with better performance for males and worse for females on fine motor skills. The METH-dependent individuals in this population exhibit very limited cognitive impairment. The marked differences in education, Intellectual Quotient (IQ), and gender in our sample when compared to the published literature may contribute to these findings. Characterization of the impact of clinical and/or demographic features on cognitive deficits could be important in guiding the development of treatment interventions.

  18. Assessing Correlates of the Growth and Extent of Methamphetamine Abuse and Dependence in California

    PubMed Central

    Gruenewald, Paul J.; Johnson, Fred W.; Ponicki, William R.; Remer, Lillian G.; LaScala, Elizabeth A.

    2013-01-01

    Using aggregate-level data, this study performed cross-sectional analyses on all 1,628 populated California zip code areas and longitudinal analyses on 581 consistently defined zip codes over six years (1995– 2000), relating place and population characteristics of these areas to rates of hospital discharges for amphetamine dependence/abuse using linear spatial models. Analyzing the data in two ways, spatial time series cross-sections and spatial difference models, amphetamine dependence/abuse were greatest in rural areas with more young low-income whites, larger numbers of retail and alcohol outlets, and smaller numbers of restaurants. Growth rates of these problems were greater in areas with higher income and larger non-White and Hispanic populations. This suggests that there was some change in the penetration of the methamphetamine epidemic into different population groups during this time. Study implications and limitations are discussed. PMID:20380553

  19. Assessing correlates of the growth and extent of methamphetamine abuse and dependence in California.

    PubMed

    Gruenewald, Paul J; Johnson, Fred W; Ponicki, William R; Remer, Lillian G; Lascala, Elizabeth A

    2010-10-01

    Using aggregate-level data, this study performed cross-sectional analyses on all 1,628 populated California zip code areas and longitudinal analyses on 581 consistently defined zip codes over six years (1995-2000), relating place and population characteristics of these areas to rates of hospital discharges for amphetamine dependence/abuse using linear spatial models. Analyzing the data in two ways, spatial time series cross-sections and spatial difference models, amphetamine dependence/abuse were greatest in rural areas with more young low-income whites, larger numbers of retail and alcohol outlets, and smaller numbers of restaurants. Growth rates of these problems were greater in areas with higher income and larger non-White and Hispanic populations. This suggests that there was some change in the penetration of the methamphetamine epidemic into different population groups during this time. Study implications and limitations are discussed.

  20. Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

    PubMed

    Rezaei, Farzin; Ghaderi, Ebrahim; Mardani, Roya; Hamidi, Seiran; Hassanzadeh, Kambiz

    2016-06-01

    To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P < 0.001) and drug need (P < 0.001). Furthermore, the craving score (duration) significantly declined in the topiramate patients compared to those receiving the placebo. In conclusion, the results of this trial suggest that topiramate may be beneficial for the treatment of methamphetamine dependence.

  1. 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).

  2. HIV infection Heightens Concurrent Risk of Functional Dependence in Persons With Chronic Methamphetamine Use

    PubMed Central

    Blackstone, K.; Iudicello, J. E.; Morgan, E. E.; Weber, E.; Moore, D. J.; Franklin, D. R.; Ellis, R. J.; Grant, I.; Woods, S. P.

    2013-01-01

    Objectives The causes of disability among chronic methamphetamine (MA) users are multifactorial. The current study examined the additive adverse impact of human immunodeficiency virus (HIV) infection, a common comorbidity in MA users, on functional dependence. Methods A large cohort of participants (N=798) stratified by lifetime MA dependence diagnoses (i.e., MA+ or MA−) and HIV serostatus (i.e., HIV+ or HIV−) underwent comprehensive baseline neuromedical, neuropsychiatric, and functional research evaluations, including assessment of neurocognitive symptoms in daily life, instrumental and basic activities of daily living, and employment status. Results Independent, additive effects of MA and HIV were observed across all measures of functional dependence, independent of other demographic, psychiatric, and substance use factors. The prevalence of global functional dependence increased in the expected stepwise fashion across the cohort, with the lowest rates in the MA−/HIV− group (29%) and the highest rates in the MA+/HIV+ sample (69%). The impact of HIV on MA-associated functional dependence was moderated by nadir CD4 count, such that MA use was associated with greater disability among those HIV-infected persons with higher, but not lower nadir CD4. Within the MA+/HIV+ cohort, functional dependence was reliably associated with neurocognitive impairment, lower cognitive reserve, polysubstance use, and major depressive disorder. Conclusions HIV infection confers an increased concurrent risk of MA-associated disability, particularly among HIV-infected persons without histories of immune compromise. Directed referrals, earlier HIV treatment, and compensatory strategies aimed at counteracting the effects of low cognitive reserve, neurocognitive impairment, and psychiatric comorbidities on functional dependence in MA+/HIV+ individuals may be warranted. PMID:23648641

  3. Dynamic Indices of Methamphetamine Dependence and HIV Infection Predict Fluctuations in Affective Distress: A Five-year Longitudinal Analysis

    PubMed Central

    Montoya, Jessica L.; Umlauf, Anya; Abramson, Ian; Badiee, Jayraan; Woods, Steven Paul; Atkinson, J. Hampton; Grant, Igor; Moore, David J.

    2013-01-01

    Background Methamphetamine (METH) use and human immunodeficiency virus (HIV) infection are highly comorbid, and both are associated with increased prevalence of affective distress. Delineating the trajectory of affective distress in the context of METH dependence and HIV infection is important given the implications for everyday functional impairment, adverse health behaviors, and increased risk for adverse health outcomes. Methods We conducted a five-year longitudinal investigation involving 133 METH-dependent (74 HIV seropositive) and 163 non-METH-dependent (90 HIV seropositive) persons to examine both long-standing patterns and transient changes in affective distress. Mixed-effect regression models with random subject-specific slopes and intercepts evaluated the effect of METH dependence, HIV serostatus, and related variables on affective distress, as measured by the Profile of Mood States. Results Transient changes in affective distress were found to be greater among those with a diagnosis of current MDD, briefer durations of abstinence from METH, and higher quantity of METH consumed. Weak associations were observed among static (time-independent predictors) covariates and long-standing patterns in affective distress. Limitations Study lacked data pertaining to the participants’ involvement in METH treatment and relied on respondent-driven sampling. Conclusions Our longitudinal investigation of the trajectory of affective distress indicated that specific and dynamic indices of current METH use were associated with greater transient changes in mood. In the evaluation and treatment of affective distress, recency and quantity of current METH use are important to consider given their association with heightened affective distress and mood instability over time. PMID:24012068

  4. Elevated intraindividual variability in methamphetamine dependence is associated with poorer everyday functioning.

    PubMed

    Morgan, Erin E; Doyle, Katie L; Minassian, Arpi; Henry, Brook L; Perry, William; Marcotte, Thomas D; Woods, Steven Paul; Grant, Igor

    2014-12-15

    Methamphetamine (MA) dependence is associated with executive dysfunction, but no studies have evaluated MA-related elevations in neurocognitive intraindividual variability (IIV), an expression of cognitive dyscontrol linked to poor daily functioning in populations with frontal systems injury. We examined IIV during a vigilance task in a well-characterized sample of 35 MA-dependent (MA+) and 55 non-MA using comparison participants (MA-) as part of a larger neuropsychological battery that included self-report and performance-based measures of everyday functioning. A mixed model ANOVA was conducted while controlling for covariates, including factors that differed between the groups (e.g., education) and those with conceptual relevance to IIV: mean reaction time, global cognitive performance, and HIV-infection (which was comparable across groups; p=0.32). This analysis revealed significantly elevated IIV among MA+ relative to MA- individuals that was comparable in magnitude across all trial blocks of the vigilance task. Within the MA group, elevated IIV was associated with executive dysfunction, psychomotor slowing, and recency of MA use, as well as poorer automobile driving simulator performance, worse laboratory-based functional skills, and more cognitive complaints. MA-users are vulnerable to IIV elevation, likely due to cognitive dyscontrol, which may increase their risk of real-world problems.

  5. Elevated intraindividual variability in methamphetamine dependence is associated with poorer everyday functioning

    PubMed Central

    Morgan, Erin E.; Doyle, Katie L.; Minassian, Arpi; Henry, Brook; Perry, William; Marcotte, Thomas D.; Woods, Steven Paul; Grant, Igor

    2014-01-01

    Methamphetamine (MA) dependence is associated with executive dysfunction, but no studies have evaluated MA-related elevations in neurocognitive intraindividual variability (IIV), an expression of cognitive dyscontrol linked to poor daily functioning in populations with frontal systems injury. We examined IIV during a vigilance task in a well-characterized sample of 35 MA-dependent (MA+) and 55 non-MA using comparison participants (MA−) as part of a larger neuropsychological battery that included self-report and performance-based measures of everyday functioning. A mixed model ANOVA was conducted while controlling for covariates, including factors that differed between the groups (e.g., education) and those with conceptual relevance to IIV: mean reaction time, global cognitive performance, and HIV-infection (which was comparable across groups; p = .32). This analysis revealed significantly elevated IIV among MA+ relative to MA− individuals that was comparable in magnitude across all trial blocks of the vigilance task. Within the MA group, elevated IIV was associated with executive dysfunction, psychomotor slowing, and recency of MA use, as well as poorer automobile driving simulator performance, worse laboratory-based functional skills, and more cognitive complaints. MA-users are vulnerable to IIV elevation, likely due to cognitive dyscontrol, which may increase their risk of real-world problems. PMID:25081313

  6. Predictors of Attrition in a Cohort Study of HIV Infection and Methamphetamine Dependence

    PubMed Central

    Cattie, J.; Marquine, M. J.; Bolden, K. A.; Obermeit, L. C.; Morgan, E. E.; Franklin, D. R.; Umlauf, A; Beck, J. M.; Atkinson, J. H.; Grant, I.; Woods, S. P.

    2015-01-01

    Longitudinal cohort studies of HIV and substance use disorders play an important role in understanding these conditions, but high rates of attrition can threaten their integrity and generalizability. This study aimed to identify factors associated with attrition in a 5-year observational cohort study of 469 individuals with and without HIV infection and methamphetamine (MA) dependence. Rates of attrition in our four study groups were approximately 24% in HIV-MA-, 15% in HIV+MA-, 56% in HIV-MA+, and 47% in HIV+MA+ individuals. Predictors of attrition in the overall cohort included history of MA, alcohol, and other substance dependence, learning impairment, reduced cognitive reserve, and independence in activities of daily living (all ps < .05), but varied somewhat by clinical group. Of particular note, enrollment in a neuroimaging substudy was associated with significantly boosted rates of retention in the MA groups. Results from this investigation highlight the complexity of the clinical factors that influence retention in cohort studies of HIV-infected MA users and might guide the development and implementation of targeted retention efforts. PMID:26752974

  7. Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women.

    PubMed

    van der Plas, Ellen A A; Crone, Eveline A; van den Wildenberg, Wery P M; Tranel, Daniel; Bechara, Antoine

    2009-08-01

    Substance dependence is associated with executive function deficits, but the nature of these executive defects and the effect that different drugs and sex have on these defects have not been fully clarified. Therefore, we compared the performance of alcohol- (n = 33; 18 women), cocaine- (n = 27; 14 women), and methamphetamine-dependent individuals (n = 38; 25 women) with sex-matched healthy comparisons (n = 36; 17 women) on complex decision making as measured with the Iowa Gambling Task, working memory, cognitive flexibility, and response inhibition. Cocaine- and methamphetamine-dependent individuals were impaired on complex decision making, working memory, and cognitive flexibility, but not on response inhibition. The deficits in working memory and cognitive flexibility were milder than the decision-making deficits and did not change as a function of memory load or task switching. Interestingly, decision making was significantly more impaired in women addicted to cocaine or methamphetamine than in men addicted to these drugs. Together, these findings suggest that drug of choice and sex have different effects on executive functioning, which, if replicated, may help tailor intervention.

  8. Striatal Volume Increases in Active Methamphetamine-Dependent Individuals and Correlation with Cognitive Performance

    PubMed Central

    Jan, Reem K.; Lin, Joanne C.; Miles, Sylvester W.; Kydd, Rob R.; Russell, Bruce R.

    2012-01-01

    The effect of methamphetamine (MA) dependence on the structure of the human brain has not been extensively studied, especially in active users. Previous studies reported cortical deficits and striatal gains in grey matter (GM) volume of abstinent MA abusers compared with control participants. This study aimed to investigate structural GM changes in the brains of 17 active MA-dependent participants compared with 20 control participants aged 18–46 years using voxel-based morphometry and region of interest volumetric analysis of structural magnetic resonance imaging data, and whether these changes might be associated with cognitive performance. Significant volume increases were observed in the right and left putamen and left nucleus accumbens of MA-dependent compared to control participants. The volumetric gain in the right putamen remained significant after Bonferroni correction, and was inversely correlated with the number of errors (standardised z-scores) on the Go/No-go task. MA-dependent participants exhibited cortical GM deficits in the left superior frontal and precentral gyri in comparison to control participants, although these findings did not survive correction for multiple comparisons. In conclusion, consistent with findings from previous studies of abstinent users, active chronic MA-dependent participants showed significant striatal enlargement which was associated with improved performance on the Go/No-go, a cognitive task of response inhibition and impulsivity. Striatal enlargement may reflect the involvement of neurotrophic effects, inflammation or microgliosis. However, since it was associated with improved cognitive function, it is likely to reflect a compensatory response to MA-induced neurotoxicity in the striatum, in order to maintain cognitive function. Follow-up studies are recommended to ascertain whether this effect continues to be present following abstinence. Several factors may have contributed to the lack of more substantial cortical and

  9. Neurofeedback Training as a New Method in Treatment of Crystal Methamphetamine Dependent Patients: A Preliminary Study.

    PubMed

    Rostami, R; Dehghani-Arani, F

    2015-09-01

    This study aimed to compare the effectiveness of neurofeedback (NFB) plus pharmacotherapy with pharmacotherapy alone, on addiction severity, mental health, and quality of life in crystal methamphetamine-dependent (CMD) patients. The study included 100 CMD patients undergoing a medical treatment who volunteered for this randomized controlled trial. After being evaluated by a battery of questionnaires that included addiction severity index questionnaire, Symptoms Check List 90 version, and World Health Organization Quality of Life, the participants were randomly assigned to an experimental or a control group. The experimental group received thirty 50-min sessions of NFB in addition to their usual medication over a 2-month period; meanwhile, the control group received only their usual medication. In accordance with this study's pre-test-post-test design, both study groups were evaluated again after completing their respective treatment regimens. Multivariate analysis of covariance showed the experimental group to have lower severity of addiction, better psychological health, and better quality of life in than the control group. The differences between the two groups were statistically significant. These finding suggest that NFB can be used to improve the effectiveness of treatment results in CMD patients.

  10. Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence

    PubMed Central

    Heinzerling, Keith G.; Swanson, Aimee-Noelle; Kim, Soeun; Cederblom, Lisa; Moe, Ardis; Ling, Walter; Steven, Shoptaw

    2010-01-01

    Objective To compare modafinil to placebo for reducing methamphetamine (MA) use, improving retention, and reducing depressive symptoms and MA cravings. Rates of adverse events and cigarette smoking with modafinil versus placebo were also compared. Methods Following a 2-week, non-medication lead-in period, 71 treatment-seeking MA dependent participants were randomly assigned to modafinil (400 mg once daily; N= 34) or placebo (once daily; N= 37) for 12-weeks under double-blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research assessments, and to receive contingency management and weekly cognitive behavioral therapy (CBT) sessions. Results There were no statistically significant effects for modafinil on MA use, retention, depressive symptoms, or MA cravings in pre-planned analyses. Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high frequency of MA use (MA use on >18 of past 30 days), but did not reach statistical significance in these small subgroups. Modafinil was safe and well tolerated and did not increase cigarette smoking. Conclusions Modafinil was no more effective than placebo at 400 mg daily in a general sample of MA users. A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted. PMID:20092966

  11. Psychometric properties of the Barratt Impulsiveness Scale in patients with gambling disorders, hypersexuality, and methamphetamine dependence.

    PubMed

    Reid, Rory C; Cyders, Melissa A; Moghaddam, Jacquelene F; Fong, Timothy W

    2014-11-01

    Although the Barratt Impulsiveness Scale (BIS; Patton, Stanford, & Barratt, 1995) is a widely-used self-report measure of impulsivity, there have been numerous questions about the invariance of the factor structure across clinical populations (Haden & Shiva, 2008, 2009; Ireland & Archer, 2008). The goal of this article is to examine the factor structure of the BIS among a sample consisting of three populations exhibiting addictive behaviors and impulsivity: pathological gamblers, hypersexual patients, and individuals seeking treatment for methamphetamine dependence to determine if modification to the existing factors might improve the psychometric properties of the BIS. The current study found that the factor structure of the BIS does not replicate in this sample and instead produces a 12-item three-factor solution consisting of motor-impulsiveness (5 items), non-planning impulsiveness (3 items), and immediacy impulsiveness (4 items). The clinical utility of the BIS in this population is questionable. The authors suggest future studies to investigate comparisons with this modified version of the BIS and other impulsivity scales such as the UPPS-P Impulsive Behavior Scale in clinical populations when assessing disposition toward rash action.

  12. The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study.

    PubMed

    Ray, Lara A; Bujarski, Spencer; Courtney, Kelly E; Moallem, Nathasha R; Lunny, Katy; Roche, Daniel; Leventhal, Adam M; Shoptaw, Steve; Heinzerling, Keith; London, Edythe D; Miotto, Karen

    2015-09-01

    Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

  13. Altered Statistical Learning and Decision-Making in Methamphetamine Dependence: Evidence from a Two-Armed Bandit Task.

    PubMed

    Harlé, Katia M; Zhang, Shunan; Schiff, Max; Mackey, Scott; Paulus, Martin P; Yu, Angela J

    2015-01-01

    Understanding how humans weigh long-term and short-term goals is important for both basic cognitive science and clinical neuroscience, as substance users need to balance the appeal of an immediate high vs. the long-term goal of sobriety. We use a computational model to identify learning and decision-making abnormalities in methamphetamine-dependent individuals (MDI, n = 16) vs. healthy control subjects (HCS, n = 16), in a two-armed bandit task. In this task, subjects repeatedly choose between two arms with fixed but unknown reward rates. Each choice not only yields potential immediate reward but also information useful for long-term reward accumulation, thus pitting exploration against exploitation. We formalize the task as comprising a learning component, the updating of estimated reward rates based on ongoing observations, and a decision-making component, the choice among options based on current beliefs and uncertainties about reward rates. We model the learning component as iterative Bayesian inference (the Dynamic Belief Model), and the decision component using five competing decision policies: Win-stay/Lose-shift (WSLS), ε-Greedy, τ-Switch, Softmax, Knowledge Gradient. HCS and MDI significantly differ in how they learn about reward rates and use them to make decisions. HCS learn from past observations but weigh recent data more, and their decision policy is best fit as Softmax. MDI are more likely to follow the simple learning-independent policy of WSLS, and among MDI best fit by Softmax, they have more pessimistic prior beliefs about reward rates and are less likely to choose the option estimated to be most rewarding. Neurally, MDI's tendency to avoid the most rewarding option is associated with a lower gray matter volume of the thalamic dorsal lateral nucleus. More broadly, our work illustrates the ability of our computational framework to help reveal subtle learning and decision-making abnormalities in substance use.

  14. Altered Statistical Learning and Decision-Making in Methamphetamine Dependence: Evidence from a Two-Armed Bandit Task

    PubMed Central

    Harlé, Katia M.; Zhang, Shunan; Schiff, Max; Mackey, Scott; Paulus, Martin P.; Yu, Angela J.

    2015-01-01

    Understanding how humans weigh long-term and short-term goals is important for both basic cognitive science and clinical neuroscience, as substance users need to balance the appeal of an immediate high vs. the long-term goal of sobriety. We use a computational model to identify learning and decision-making abnormalities in methamphetamine-dependent individuals (MDI, n = 16) vs. healthy control subjects (HCS, n = 16), in a two-armed bandit task. In this task, subjects repeatedly choose between two arms with fixed but unknown reward rates. Each choice not only yields potential immediate reward but also information useful for long-term reward accumulation, thus pitting exploration against exploitation. We formalize the task as comprising a learning component, the updating of estimated reward rates based on ongoing observations, and a decision-making component, the choice among options based on current beliefs and uncertainties about reward rates. We model the learning component as iterative Bayesian inference (the Dynamic Belief Model), and the decision component using five competing decision policies: Win-stay/Lose-shift (WSLS), ε-Greedy, τ-Switch, Softmax, Knowledge Gradient. HCS and MDI significantly differ in how they learn about reward rates and use them to make decisions. HCS learn from past observations but weigh recent data more, and their decision policy is best fit as Softmax. MDI are more likely to follow the simple learning-independent policy of WSLS, and among MDI best fit by Softmax, they have more pessimistic prior beliefs about reward rates and are less likely to choose the option estimated to be most rewarding. Neurally, MDI's tendency to avoid the most rewarding option is associated with a lower gray matter volume of the thalamic dorsal lateral nucleus. More broadly, our work illustrates the ability of our computational framework to help reveal subtle learning and decision-making abnormalities in substance use. PMID:26733906

  15. Epigenetic alterations in the brain associated with HIV-1 infection and methamphetamine dependence.

    PubMed

    Desplats, Paula; Dumaop, Wilmar; Cronin, Peter; Gianella, Sara; Woods, Steven; Letendre, Scott; Smith, David; Masliah, Eliezer; Grant, Igor

    2014-01-01

    HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions.

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

    PubMed

    Fletcher, Jesse B; Reback, Cathy J

    2013-09-01

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

  17. Personality Characteristics of Adolescents with Hallucinogen, Methamphetamine, and Cannabis Dependence: A Comparative Study

    ERIC Educational Resources Information Center

    Palmer, Glen A.; Daiss, Doyle D.

    2005-01-01

    A comparison of personality factors on scales of the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) was conducted with a sample of adolescents referred to a residential substance abuse treatment program. A total of sixty adolescents identified with hallucinogen (n = 20), cannabis (n = 20), or methamphetamine (n = 20) as their drug…

  18. The Effects of BDNF Val66Met Gene Polymorphism on Serum BDNF and Cognitive Function in Methamphetamine-Dependent Patients and Normal Controls: A Case-Control Study.

    PubMed

    Su, Hang; Tao, Jingyan; Zhang, Jie; Xie, Ying; Wang, Yue; Zhang, Yu; Han, Bin; Lu, Yuling; Sun, Haiwei; Wei, Youdan; Zou, Shengzhen; Wu, Wenxiu; Zhang, Jiajia; Xu, Ke; Zhang, Xiangyang; He, Jincai

    2015-10-01

    Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may contribute to methamphetamine dependence. We hypothesized that this polymorphism had a role in cognitive deficits in methamphetamine-dependent patients and in the relationship of serum BDNF with cognitive impairments. We conducted a case-control study by assessing 194 methamphetamine-dependent patients and 378 healthy volunteers without history of drug use on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We showed no significant differences in genotype and allele distributions between the methamphetamine-dependent patients and controls. Some aspects of cognitive function significantly differed in the 2 groups. The serum BDNF levels in methamphetamine-dependent patients were significantly higher than those of the healthy controls. In the patients, partial correlation analysis showed a significant positive correlation between serum BDNF and the delayed memory index score. The RBANS scores showed statistically significant BDNF level × genotype interaction. Further regression analyses showed a significant positive association between BDNF levels and the RBANS total score, immediate memory or attention index among Val homozygote patients, whereas a significant negative association of BDNF levels with the RBANS total score, visuospatial/constructional, or language index was found among Met/Val heterozygous patients. We demonstrated significant impairment on some aspects of cognitive function and increased BDNF levels in methamphetamine-dependent patients as well as genotypic differences in the relationships between BDNF levels and RBANS scores on the BDNF Val66Met polymorphism only in these patients.

  19. Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal

    PubMed Central

    Ren, Wenwei; Tao, Jingyan; Wei, Youdan; Su, Hang; Zhang, Jie; Xie, Ying; Guo, Jun; Zhang, Xiangyang; Zhang, Hailing; He, Jincai

    2016-01-01

    Abstract Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal. 179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only). Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28 ± 490.69 vs 1241.27 ± 335.52 pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70 ± 580.59 vs 1621.41 ± 591.07 pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70 ± 580.59 vs 1241.27 ± 335.52 pg/mL; F = 2.29, P = 0.13). Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal. PMID:26844469

  20. Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal.

    PubMed

    Ren, Wenwei; Tao, Jingyan; Wei, Youdan; Su, Hang; Zhang, Jie; Xie, Ying; Guo, Jun; Zhang, Xiangyang; Zhang, Hailing; He, Jincai

    2016-02-01

    Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal.179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only).Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28  ±  490.69 vs 1241.27  ±  335.52  pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70  ±  580.59 vs 1621.41  ±  591.07  pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70  ±  580.59 vs 1241.27  ±  335.52  pg/mL; F = 2.29, P = 0.13).Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal.

  1. 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.

  2. 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

  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. Black agouti (ACI) rats show greater drug- and cue-induced reinstatement of methamphetamine-seeking behavior than Fischer 344 and Lewis rats.

    PubMed

    Xi, Jinlei; Kruzich, Paul J

    2007-05-01

    Fischer 344 (F344) and Lewis (LEW) rats differ in methamphetamine self-administration (SA) and methamphetamine-induced reinstatement of previously extinguished behavior. We sought to determine whether genetic background also influences methamphetamine reinforcement efficacy, conditioned reinstatement, and methamphetamine-primed reinstatement of responding in F344, LEW, and Black Agouti (ACI) rats. We implanted rats with jugular catheters and trained them to self-administer methamphetamine (0.06 mg/kg/infusion) under a progressive ratio (PR) schedule of reinforcement during daily 2-h SA sessions. A compound stimulus (light+tone; LT) was paired with each infusion. Dose-dependent intake was determined for each rat. Rats then entered the extinction phase of the experiment where responding resulted in no programmed consequences. Following extinction sessions, rats underwent conditioned reinstatement testing. For conditioned reinstatement, rats received response-contingent presentations of the LT and no methamphetamine. Last, methamphetamine-primed reinstatement test sessions where conducted where subjects received experimenter delivered infusions of methamphetamine (0.06, 0.12, or 0.24 mg/kg). The strains did not differ in PR responding across the doses tested. The ACI rats demonstrated the highest behavioral output during extinction training, conditioned- and methamphetamine-primed reinstatement of previously extinguished behavior compared to the other strains. These data suggest that genetic background differentially influences extinction, conditioned reinstatement and methamphetamine-primed reinstatement in rats.

  5. 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.

  6. 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

  7. Impact of prospectively-determined A118G polymorphism on treatment response to injectable naltrexone among methamphetamine-dependent patients: An open-label, pilot study

    PubMed Central

    Pal, Reshmi; Mendelson, John E.; Flower, Keith; Garrison, Kathleen; Yount, Garret; Coyle, Jeremy R.; Galloway, Gantt P.

    2015-01-01

    Objectives Methamphetamine (MA) addiction has no known effective pharmacotherapy. Small trials showed beneficial effects for oral naltrexone in amphetamine users. Trials in alcohol dependent subjects showed better response in persons with the A118G single nucleotide polymorphism (SNP) of the µ-opioid receptor. We conducted a pharmacogenetic trial of sustained release intramuscular naltrexone to examine the role of the A118G SNP in MA dependence. Method All eligible A118G subjects screened were enrolled; an equal number of wild type (A118A) subjects were selected using modified urn randomization, balanced on gender and frequency of recent MA use. Enrolled subjects received a single 380 mg naltrexone injection and weekly psychotherapy for four weeks. Self-report of MA use and urine toxicology for MA was assessed twice weekly. Urine samples with <1,000 ng/mL of MA were considered negative. Results Eleven A118G and 11 A118A subjects were enrolled. There were no significant differences between the groups in days of abstinence from MA use (11.5 v. 14.8, respectively, p = 0.51), number of MA-negative urine samples (1.7 v. 1.8, respectively, p = 0.97), consecutive MA-negative urine samples (1.0 v. 1.5, respectively, p = 0.91), or number of MA-negative urine samples before first relapse (0.9 v. 1.5, respectively, p = 0.86). Conclusions Although A118G polymorphism has been shown to be associated with improved treatment response to naltrexone among alcoholics, whether this polymorphism impacts naltrexone treatment response among MA users is unclear at this time. PMID:25622123

  8. Methamphetamine (Meth)

    MedlinePlus

    ... from heart attack or stroke caused by the drug’s effects on the neurotransmitter norepinephrine, which raises heart beat ... know that methamphetamine is "worse" than any other drug, but its effects can last longer than some. I think the ...

  9. Methamphetamine (Meth)

    MedlinePlus

    ... but will still get the rest of the drug's effects. After the first rush, a meth high is ... away, even after a user stops taking the drug. One well-known effect of methamphetamine use is severe dental problems, also ...

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

    PubMed

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

    2005-12-15

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

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

    SciTech Connect

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

    2005-12-15

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

  12. Gravity dependence of subjective visual vertical variability.

    PubMed

    Tarnutzer, A A; Bockisch, C; Straumann, D; Olasagasti, I

    2009-09-01

    The brain integrates sensory input from the otolith organs, the semicircular canals, and the somatosensory and visual systems to determine self-orientation relative to gravity. Only the otoliths directly sense the gravito-inertial force vector and therefore provide the major input for perceiving static head-roll relative to gravity, as measured by the subjective visual vertical (SVV). Intraindividual SVV variability increases with head roll, which suggests that the effectiveness of the otolith signal is roll-angle dependent. We asked whether SVV variability reflects the spatial distribution of the otolithic sensors and the otolith-derived acceleration estimate. Subjects were placed in different roll orientations (0-360 degrees, 15 degrees steps) and asked to align an arrow with perceived vertical. Variability was minimal in upright, increased with head-roll peaking around 120-135 degrees, and decreased to intermediate values at 180 degrees. Otolith-dependent variability was modeled by taking into consideration the nonuniform distribution of the otolith afferents and their nonlinear firing rate. The otolith-derived estimate was combined with an internal bias shifting the estimated gravity-vector toward the body-longitudinal. Assuming an efficient otolith estimator at all roll angles, peak variability of the model matched our data; however, modeled variability in upside-down and upright positions was very similar, which is at odds with our findings. By decreasing the effectiveness of the otolith estimator with increasing roll, simulated variability matched our experimental findings better. We suggest that modulations of SVV precision in the roll plane are related to the properties of the otolith sensors and to central computational mechanisms that are not optimally tuned for roll-angles distant from upright.

  13. Differences in maternal behavior and development of their pups depend on the time of methamphetamine exposure during gestation period.

    PubMed

    Malinová-Ševčíková, M; Hrebíčková, I; Macúchová, E; Nová, E; Pometlová, M; Šlamberová, R

    2014-01-01

    The present study examined the hypothesis that the extension of noxious effect of methamphetamine (MA) on maternal behavior and postnatal development on the pups may differ in dependence with time of application. Female rats were injected with MA (5 mg/kg) or saline during first (embryonic day (ED) 1-11) or second (ED 12-22) half of gestation. Our results demonstrated that MA exposure on ED 12-22 led to decreased birth weight and weight gained during lactation period relative to rats treated on ED 1-11. Both sexes treated prenatally with MA on ED 1-11 opened eyes earlier compared to animals treated on ED 12-22. As a matter of sensorimotor development application of MA on ED 1-11 impaired the righting reflex, while MA exposure on ED 12-22 impaired the performance of beam balance test in male rats. There were no differences in maternal behavior. Therefore, it seems that MA exposure in the first half of the gestation impaired the early sensorimotor development that is under control of the brain stem, while the MA exposure in the second half of gestation affected the beam balance performance that is dependent on the function of the cerebellum.

  14. The effects of modafinil treatment on neuropsychological and attentional bias performance during 7-day inpatient withdrawal from methamphetamine dependence.

    PubMed

    Hester, Robert; Lee, Nicole; Pennay, Amy; Nielsen, Suzi; Ferris, Jason

    2010-12-01

    The cognitive benefits of modafinil to patients undergoing 7-day inpatient withdrawal from methamphetamine (MA) dependence were examined as part of a double-blind, randomized, placebo-controlled pilot trial. Recent evidence has identified modafinil-related improvements in treatment outcomes for MA-dependent patients; however, the benefits to cognition function, which is critical to treatment success but known to be impaired, has yet to be examined. The first 20 participants recruited to the study were administered either 200 mg of modafinil (once daily) or placebo, and a neuropsychological test battery (including an MA version of the emotional Stroop task) at admission (n = 17) and discharge (n = 14). Follow-up interviews were conducted at 1-month postdischarge (n = 13). After participant withdrawals (3 in each group), treatment was associated with a significant improvement in immediate verbal memory recall and nonsignificant trend toward improvement on executive function and delayed memory tasks. No benefit was seen for measures of verbal learning, visual memory, processing speed, or verbal fluency. All participants showed a significant attentional bias for MA-related stimuli on the emotional Stroop task. The magnitude of bias predicted both retention in treatment and relapse potential at follow-up but was not significantly ameliorated by modafinil treatment. While nonsignificant, the effect sizes of modafinil-related improvements in executive function and memory were consistent with those found in more robustly powered studies of cognitive benefits in attention-deficit/hyperactivity disorder and schizophrenia, supporting the need for further research.

  15. Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5'-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study.

    PubMed

    Yoon, Sujung J; Lyoo, In Kyoon; Kim, Hengjun J; Kim, Tae-Suk; Sung, Young Hoon; Kim, Namkug; Lukas, Scott E; Renshaw, Perry F

    2010-04-01

    Cytidine-5'-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy ((1)H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n=16) or placebo (n=15) for 4 weeks. Prefrontal NAA and Cho levels were examined using (1)H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p=0.005) and Cho (p=0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p=0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence.

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

    PubMed

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

    2017-03-01

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

  17. Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence

    PubMed Central

    Ballard, Michael E.; Mandelkern, Mark A.; Monterosso, John R.; Hsu, Eustace; Robertson, Chelsea L.; Ishibashi, Kenji; Dean, Andy C.

    2015-01-01

    Background: Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence. Methods: Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [18F]fallypride. Results: MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5). Conclusions: These results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed. PMID:25603861

  18. An Investigation of Cigarettes Smoking Behavior and Nicotine Dependence among Chinese Methamphetamine Users in Two Provinces

    PubMed Central

    Wang, Ziyun; Bao, Yanping; Yan, Shiyan; Lian, Zhi; Jia, Zhenjun; Liu, Zhimin

    2014-01-01

    Objective. To survey cigarette behaviors and nicotine dependence among Chinese MA users, explore risk factors for high nicotine dependence, and analyze the relationship between nicotine dependence and MA-related euphoria and sexual impulse. Methods. A cross-sectional study, applying a self-designed questionnaire with the Fagerström Test for Nicotine Dependence (FTND) and Visual Analog Scale (VAS), was performed among 391 MA users in Beijing and Guangdong, China. Results. Most MA users were smokers, including 159 having high dependence on nicotine (HD users, FTND > 5) and 197 low or medium dependent (LMD users, FTND ≤ 5). Men or married users were more likely to be highly dependent than women or unmarried users. Higher MA dose and ever-use of ketamine or alcohol were associated with higher likelihood of high nicotine dependence. HD users reported significantly higher euphoria and stronger sexual impulse after using MA, indicated by higher VAS scores. Conclusions. Potential risk factors for high nicotine dependence among MA users may include male gender, being married, higher MA dosage, and ever-use of ketamine or alcohol, which should be taken into consideration in individualized health promotion on smoking cessation. Severe nicotine dependence was associated with stronger MA-related euphoria and sexual impulse and it should be confirmed by further studies. PMID:25025035

  19. 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

  20. 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.

  1. Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: Link to impulsivity in methamphetamine users

    PubMed Central

    Kohno, Milky; Okita, Kyoji; Morales, Angelica M.; Robertson, Chelsea; Dean, Andy C.; Ghahremani, Dara G.; Sabb, Fred; Mandelkern, Mark A.; Bilder, Robert M.; London, Edythe D.

    2015-01-01

    Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC), and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between midbrain and striatum, orbitofrontal cortex, and insula in methamphetamine-dependent participants but a positive relationship in the control group. In Study 2, an interaction of group with RSFC on impulsivity was observed. Methamphetamine-dependent participants users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals. PMID:26830141

  2. Methylphenidate vs. resperidone in treatment of methamphetamine dependence: A clinical trial

    PubMed Central

    Solhi, Hassan; Jamilian, Hamid Reza; Kazemifar, Amir Mohammad; Javaheri, Javad; Rasti Barzaki, Akram

    2013-01-01

    Background and aims Currently, there is no widely accepted evidence-based pharmacotherapy regime for the treatment of psychostimulant dependence. Yet, different pharmacological approaches have been tried in the treatment of MA addiction. The present study was conducted to compare efficiency of methylphenidate which is relatively easily accessible in our country, with resperidone for this purpose. Methods Eighty-six patients with MA dependence according to criteria defined by DSM IV-TR were divided into two groups. Patients in group R were given oral resperidone 1 mg daily for 1 week; then 2 mg daily in a divided dose for 3 weeks. Patients in group M were given oral methylphenidate 10 mg daily for 2 weeks, 7.5 mg daily for 1 week, then 5 mg daily for 1 week. They were evaluated for drug craving, psychological, neurologic and somatic symptoms at the start and end of the study. Findings Both drugs were useful for lowering drug craving in patients; however resperidone was more effective (6.31 ± 8.31 vs.19.6 ± 12.45 cravings per week, respectively). The effects of resperidone were more notable in lowering frequency and intensity of psychiatric, neurologic, cardiac and somatic symptoms of the patients after discontinuation of MA abuse; however methylphenidate was effective too; though with a lower potency. Conclusion The present study confirmed that both methylphenidate and resperidone can successfully be used for treatment of MA dependence, in order to reduce drug craving and psychological, neurologic, and somatic problems in patients. However, the efficacy of methylphenidate was estimated to be less than that of resperidone for this purpose. PMID:25061402

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

    PubMed

    Sirova, Jana; Kristofikova, Zdenka; Vrajova, Monika; Fujakova-Lipski, Michaela; Ripova, Daniela; Klaschka, Jan; Slamberova, Romana

    2016-08-01

    Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to

  4. Effects of environmental enrichment during induction of methamphetamine dependence on the behavioral withdrawal symptoms in rats.

    PubMed

    Hajheidari, Samira; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2015-09-25

    This study was designed to examine the effect of environmental enrichment during METH administration on the behavioral withdrawal symptoms after drug abstinence in rats. Rats reared in standard (SE) or enriched environment (EE) during induction of METH dependence with bi-daily injections of METH (2mg/kg, at 12-h. intervals) for 14 days. Then, rats were evaluated for behavioral withdrawal symptoms, and also for anxiety (elevated plus maze-EPM) and depression (Forced swim test-FST) over a ten day period of abstinence. The results showed that stereotypic behaviors score and the number of rearing were significantly lower in METH/EE rats compared to the SE group during 1-4 days. Also, The METH/EE group exhibited more weight gain during 6-10 days of abstinence. The METH/EE rats exhibited lower levels of immobility after METH abstinence than control group in the FST. EE had no effect on anxiety-like behavior. This study showed that exposure to EE diminished the severity of withdrawal symptoms and depressive-like behavior during spontaneous withdrawal from METH.

  5. 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.

  6. 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.

  7. Progressive gene dose-dependent disruption of the methamphetamine-sensitive circadian oscillator-driven rhythms in a knock-in mouse model of Huntington's disease.

    PubMed

    Ouk, Koliane; Aungier, Juliet; Morton, A Jennifer

    2016-12-01

    Huntington's disease (HD) is a progressive genetic neurodegenerative disorder characterised by motor and cognitive deficits, as well as sleep and circadian abnormalities. In the R6/2 mouse, a fragment model of HD, rest-activity rhythms controlled by the suprachiasmatic nucleus disintegrate completely by 4months of age. Rhythms driven by a second circadian oscillator, the methamphetamine-sensitive circadian oscillator (MASCO), are disrupted even earlier, and cannot be induced after 2months of age. Here, we studied the effect of the HD mutation on the expression of MASCO-driven rhythms in a more slowly developing, genetically relevant mouse model of HD, the Q175 'knock-in' mouse. We induced expression of MASCO output by administering low dose methamphetamine (0.005%) chronically via the drinking water. We measured locomotor activity in constant darkness in wild-type and Q175 mice at 2 (presymptomatic), 6 (early symptomatic), and 12 (symptomatic) months of age. At 2months, all mice expressed MASCO-driven rhythms, regardless of genotype. At older ages, however, there was a progressive gene dose-dependent deficit in MASCO output in Q175 mice. At 6months of age, these rhythms could be observed in only 45% of heterozygous and 15% of homozygous mice. By 1year of age, 90% of homozygous mice had an impaired MASCO output. There was also an age-dependent disruption of MASCO output seen in wild-type mice. The fact that the progressive deficit in MASCO-driven rhythms in Q175 mice is HD gene dose-dependent suggests that, whatever its role in humans, abnormalities in MASCO output may contribute to the HD circadian phenotype.

  8. Amphetamine and methamphetamine have a direct and differential effect on BV2 microglia cells.

    PubMed

    Shanks, R A; Anderson, J R; Taylor, J R; Lloyd, S A

    2012-12-01

    A comparative analysis of the direct effects of amphetamine and methamphetamine exposure on BV2 microglia cells in the presence and absence of cellular debris was performed. A significant dose-dependent and treatment-dependent effect of amphetamine and methamphetamine on BV2 cells was demonstrated: methamphetamine, but not amphetamine, inhibited phagocytosis, and a differential regulation of cytokines was observed in response to amphetamine and methamphetamine.

  9. 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.

  10. 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

  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. Methamphetamine Use and Pulmonary Hypertension

    MedlinePlus

    Methamphetamine Use Pulmonary & PH Hypertension Did you know that if you have used methamphetamines you are at risk for Pulmonary Hypertension? www. ... are made every year. PH in Association with Methamphetamine Use My doctor recently told me that I ...

  13. The beta-lactam antibiotic ceftriaxone inhibits physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and clorazepate in planarians.

    PubMed

    Rawls, Scott M; Cavallo, Federica; Capasso, Anna; Ding, Zhe; Raffa, Robert B

    2008-04-28

    Ceftriaxone (a beta-lactam antibiotic) has recently been identified as having the rare ability to increase the expression and functional activity of the glutamate transporter subtype 1 (GLT-1) in rat spinal cord cultures. GLT-1 has been implicated in diverse neurological disorders and in opioid dependence and withdrawal. It has been speculated that it might also be involved in the physical dependence and withdrawal of other abused drugs, but demonstration of this property can be difficult in mammalian models. Here, we demonstrate for the first time using a planarian model that ceftriaxone attenuates both the development of physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and a benzodiazepine (clorazepate) in a concentration-related manner. These results suggest that physical dependence and withdrawal from several drugs involve a common - beta-lactam-sensitive - mechanism in planarians. If these findings can be shown to extend to mammals, beta-lactam antibiotics might represent a novel pharmacotherapy or adjunct approach for treating drug abuse or serve as a template for drug discovery efforts aimed at treating drug abuse, recovery from drug abuse, or ameliorating the withdrawal from chronic use of therapeutic medications.

  14. 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

  15. 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.

  16. PREDICTORS OF INPATIENT TREATMENT COMPLETION OF SUBJECTS WITH HEROIN DEPENDENCE

    PubMed Central

    Samantaray, P.K.; Ray, R.; Chandiramani, K.

    1997-01-01

    One hundred and four subjects with heroin dependence, consecutive new admission to a ward were studied prospectively to assess treatment retention. All these subjects were admitted voluntarily after pre-admission counselling wherein treatment package (four week′s stay), ward routine, rules and regulation were explained. Socio-demographic parameters, drug use history, motivation as understood by “readiness to change”, reasons for seeking treatment were obtained. Reasons for non completion were noted. Thirty two subjects (31%) completed treatment. Out of 72 non-completers, 38 subjects (36%) left against medical advice and 34(33%) were discharged prematurely by the treating team for violating ward norms. Multivariate analysis showed that readiness to change (being in action stage), age of onset of heroin use (late), legal problems (high) and self confidence regarding recovery (high) in order of significance, predicted treatment completion. Therapeutic strategies to minimise drop-out. are discussed. PMID:21584093

  17. 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.

  18. Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: low doses induce hypolocomotion.

    PubMed

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

    2012-12-01

    The overall goal of the present study was to determine the effects of different doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four experiments were designed to test a wide range of meth doses in BALB/c female mice. In Experiment 1, we examined locomotor activity induced by an acute administration of low doses of meth (0.01 and 0.03mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3-10mg/kg). In Experiment 3, separate sets of mice were pre-treated with various meth doses once or twice (one injection/week) prior to a locomotor challenge with a low meth dose. Finally, in Experiment 4, we tested whether locomotor activation would be affected by pretreatment with a low or moderate dose of meth one month prior to the low meth dose challenge. Results show that low doses of meth induce hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior exposure to either one moderate or high dose of meth or to two, low doses of meth attenuated the hypolocomotor effect of a low meth dose one week later. This effect was also attenuated in mice tested one month after administration of a moderate meth dose. These results show that low and high doses of meth can have opposing effects on locomotor activity. Further, prior exposure to the drug leads to tolerance, rather than sensitization, of the hypolocomotor response to low meth doses.

  19. 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.

  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. Influence of aripiprazole pretreatment on the reinforcing effects of methamphetamine in humans.

    PubMed

    Stoops, William W; Bennett, J Adam; Lile, Joshua A; Sevak, Rajkumar J; Rush, Craig R

    2013-12-02

    Methamphetamine use disorders remain a significant public health concern. Methamphetamine produces its behavioral effects by facilitating release of monoamines like dopamine (DA) and serotonin (5-HT). Results from animal studies show that acute pretreatment with DA and 5-HT antagonists attenuates the effects of methamphetamine, but this area remains largely unexplored in humans. This study sought to assess whether aripiprazole, a partial agonist at D2/5-HT1A receptors and an antagonist at 5-HT2A receptors, would attenuate the reinforcing and subject-rated effects of oral methamphetamine. Seven subjects with histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 4, 8 or 16 mg) following acute pretreatment with aripiprazole (0 and 15 mg). During each Sampling Session, subjects also completed a battery of subject-rated, cardiovascular, and other performance measures. In subsequent Self-Administration Sessions, subjects were provided the opportunity to earn the previously sampled methamphetamine dose on a progressive-ratio procedure. Methamphetamine functioned as a reinforcer, and produced prototypical stimulant-like subject-rated and cardiovascular effects (e.g., increased ratings of Stimulated; elevated blood pressure). Aripiprazole reduced methamphetamine self-administration and attenuated some of the positive subject-rated effects of methamphetamine (e.g., ratings of Like Drug). These results indicate that acute aripiprazole pretreatment attenuates the abuse-related effects of methamphetamine.

  2. 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.

  3. A dysbiotic subpopulation of alcohol-dependent subjects

    PubMed Central

    de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie

    2015-01-01

    The vast majority of studies that assessed the importance of biological factors for the development of psychiatric disorders focused on processes occurring at the brain level. Alcohol-dependence is a very frequent psychiatric disorder where psycho-pharmacological interventions are only of moderate efficacy. Our laboratory has recently described that a subpopulation of alcohol-dependent subjects, that accounted for approximately 40% of individuals tested, presented with an increased intestinal permeability, with a dysbiosis, with alterations in the metabolomic content of faeces - that could play a role in the increased permeability - and finally with a more severe profile of alcohol-dependence than the other non-dysbiotic subpopulation. In this addendum, we discuss the implications of our observations for the pathophysiology of alcohol dependence where we try to discriminate which addiction dimensions are likely related to the gut microbiota alterations and whether these alterations are the cause or the consequence of drinking habits. PMID:26727422

  4. A dysbiotic subpopulation of alcohol-dependent subjects.

    PubMed

    de Timary, Philippe; Leclercq, Sophie; Stärkel, Peter; Delzenne, Nathalie

    2015-01-01

    The vast majority of studies that assessed the importance of biological factors for the development of psychiatric disorders focused on processes occurring at the brain level. Alcohol-dependence is a very frequent psychiatric disorder where psycho-pharmacological interventions are only of moderate efficacy. Our laboratory has recently described that a subpopulation of alcohol-dependent subjects, that accounted for approximately 40% of individuals tested, presented with an increased intestinal permeability, with a dysbiosis, with alterations in the metabolomic content of faeces--that could play a role in the increased permeability--and finally with a more severe profile of alcohol-dependence than the other non-dysbiotic subpopulation. In this addendum, we discuss the implications of our observations for the pathophysiology of alcohol dependence where we try to discriminate which addiction dimensions are likely related to the gut microbiota alterations and whether these alterations are the cause or the consequence of drinking habits.

  5. Context-Dependent Effects of a Single Administration of Mirtazapine on the Expression of Methamphetamine-Induced Conditioned Place Preference

    PubMed Central

    Voigt, Robin M.; Napier, T. Celeste

    2012-01-01

    Re-exposure to cues repeatedly associated with methamphetamine (Meth) can trigger Meth-seeking and relapse in the abstinent abuser. Weakening the conditioned Meth-associated memory during cue re-exposure may provide a means for relapse-reduction pharmacotherapy. Accordingly, we sought to determine if the atypical antidepressant mirtazapine disrupted the persistence of Meth-induced conditioned place preference (CPP) when administered in conjunction with re-exposure to contextual conditioning cues, and if this effect was altered by Meth being present during cue re-exposure. First, we evaluated the effect of mirtazapine on the maintenance of Meth-induced CPP during re-exposure to either the saline- or Meth-paired chamber 12 days after conditioning. Meth-conditioned rats subsequently administered mirtazapine expressed CPP independent of re-exposure to the saline- or Meth-paired chamber; but the magnitude of CPP was significantly less for mirtazapine-treated rats re-exposed to the Meth-paired chamber. Next, we evaluated the effect of mirtazapine on a “reinforced re-exposure” to the Meth-paired context. Administration of mirtazapine vehicle and Meth, prior to re-exposure to the Meth-paired chamber did not disrupt the ability of rats to demonstrate CPP 15 days after conditioning; however, CPP was disrupted when rats were administered mirtazapine and Meth prior to re-exposure to the Meth-paired chamber. These results indicate that the capacity of mirtazapine to diminish Meth-induced CPP is promoted if mirtazapine treatment is coupled with Meth administration in the Meth-associated context and thus appears to be the consequence of disrupting processes necessary to reconsolidate CPP following activation of drug-associated memories. PMID:22347852

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Does Posttraumatic Stress Disorder (PTSD) Affect Post-Treatment Methamphetamine Use?

    PubMed Central

    Glasner-Edwards, Suzette; Mooney, Larissa J.; Ang, Alfonso; Hillhouse, Maureen; Rawson, Richard

    2013-01-01

    Objective Although trauma is a well-established risk factor for substance use disorders, little is known about the association between posttraumatic stress disorder (PTSD) and treatment outcomes among methamphetamine users. In the present study, we examine the relationship between PTSD and post-treatment methamphetamine use outcomes, hospitalizations, and overall psychiatric impairment. Methods Using data from 526 adults in the largest psychosocial clinical trial of methamphetamine users conducted to date, this study examined: (1) treatment outcomes of methamphetamine users with concomitant PTSD three years after psychosocial treatment for methamphetamine dependence; and (2) PTSD symptom clusters as risk factors for post-treatment relapse to methamphetamine use. Results PTSD was associated with poorer methamphetamine use outcomes; methamphetamine use frequency throughout the 3-year follow-up was significantly greater among individuals with a PTSD diagnosis, and those with PTSD had more than five times the odds of reporting methamphetamine use in the 30 days prior to the follow-up interview, OR= 5.2, 95% CI [2.0–13.3]. Additionally, higher levels of other Axis I psychopathology were observed among methamphetamine users with PTSD. Avoidance and arousal symptoms predicted post-treatment methamphetamine use. Conclusions Addressing these high risk PTSD symptoms and syndromes in methamphetamine users may be helpful as a means of improving treatment outcomes in this population. PMID:24065875

  11. Bupropion for the Treatment of Methamphetamine Dependence in Non-Daily Users: a Randomized, Double-Blind, Placebo-Controlled Trial*

    PubMed Central

    Anderson, Ann L.; Li, Shou-Hua; Markova, Denka; Holmes, Tyson H.; Chiang, Nora; Kahn, Roberta; Campbell, Jan; Dickerson, Daniel L.; Galloway, Gantt P.; Stock, Christopher; Elkashef, Ahmed M.

    2015-01-01

    Aims Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users. Methods A randomized, double-blind, placebo-controlled trial, with 12-week treatment and 4-week follow-up, was conducted with 204 treatment-seeking participants having MA dependence per DSM-IV, who used MA on a less-than-daily basis. 104 were randomized to matched placebo and 100 to bupropion, sustained-release 150mg, twice daily. Participants were seen three times weekly to obtain urine for MA and bupropion assays, study assessments, and thrice weekly, 90-minute, group psychotherapy. There was no biomarker for placebo adherence. The primary outcome was achievement of abstinence throughout the last two weeks of treatment; ‘success’ requiring at least two urine samples during each of Weeks 11 and 12, and all samples MA-negative (<300ng/mL). Results Bupropion and placebo groups did not differ significantly in the percentage achieving abstinence for the last 2 weeks of treatment (chi-square, p=0.32). Subgroup analysis of participants with lower baseline MA use (≤18 of last 30 days before consent) also revealed no difference in success between groups (p=0.73). Medication adherence per protocol (detectable bupropion, >5ng/mL, in ≥50% of urine samples from Study Weeks 1–10 and ≥66% of urine samples from Weeks 11–12) was achieved by 47% of participants taking bupropion. Conclusions These data indicate that bupropion did not increase abstinence in dependent participants who were using MA less-than-daily. Medication non-adherence was a limitation in this trial. Psychosocial therapy remains the mainstay of treatment for MA dependence. Further research on subgroups who may respond to bupropion may be warranted. Trial Registration www.ClinicalTrials.gov : NCT00687713. PMID:25818061

  12. Detrimental impact of remote methamphetamine dependence on neurocognitive and everyday functioning in older but not younger HIV+ adults: evidence for a legacy effect?

    PubMed

    Iudicello, Jennifer E; Morgan, Erin E; Gongvatana, Assawin; Letendre, Scott L; Grant, Igor; Woods, Steven Paul

    2014-02-01

    Prior studies examining the combined adverse effects of HIV and methamphetamine (MA) on the central nervous system (CNS) have focused on younger to middle-aged adults with recent MA use diagnoses. Aging, HIV, and MA all converge on prefrontal and temporolimbic neural systems and confer independent risk for neurocognitive and functional decline. Thus, this study sought to determine the residual impact of a remote history of MA dependence on neurocognitive and real-world outcomes in older people living with HIV (PLWH). Participants included 116 older (≥50 years) and 94 younger (<40 years) adults classified into one of six study groups based on HIV serostatus (HIV+/HIV-) and lifetime histories of MA dependence (MA+/MA-): older HIV-MA- (n = 36), older HIV+MA- (n = 49), older HIV+MA+ (n = 31), younger HIV-MA- (n = 27), younger HIV+MA- (n = 33), and younger HIV+MA+ (n = 34). No participant-met criteria for current MA use disorders and histories of MA dependence were remote in both the older (average of nearly 9 years prior to evaluation) and younger (average of over 2 years prior to evaluation) HIV+MA+ groups. Findings revealed that a remote history of MA dependence exerts a significant detrimental impact on specific aspects of neurocognitive performance (e.g., memory) and a broad range of real-world functioning outcomes (e.g., employment) among older, but not younger PLWH. These results suggest that MA-associated neurotoxicity may have significant "legacy" effects on both neurocognitive and functional outcomes to which older PLWH are particularly vulnerable.

  13. Detrimental Impact of Remote Methamphetamine Dependence on Neurocognitive and Everyday Functioning in Older but not Younger HIV+ Adults: Evidence for a Legacy Effect?

    PubMed Central

    Iudicello, Jennifer E.; Morgan, Erin E.; Gongvatana, Assawin; Letendre, Scott L.; Grant, Igor; Woods, Steven Paul

    2014-01-01

    Prior studies examining the combined adverse effects of HIV and methamphetamine (MA) on the central nervous system (CNS) have focused on younger to middle-aged adults with recent MA use diagnoses. Aging, HIV, and MA all converge on prefrontal and temporolimbic neural systems and confer independent risk for neurocognitive and functional decline. Thus, this study sought to determine the residual impact of a remote history of MA dependence on neurocognitive and real-world outcomes in older people living with HIV (PLWH). Participants included 116 older (≥50 years) and 94 younger (<40 years) adults classified into one of six study groups based on HIV serostatus (HIV+/HIV-) and lifetime histories of MA dependence (MA+/MA-): Older HIV-MA- (n=36), Older HIV+MA- (n=49), Older HIV+MA+ (n=31), Younger HIV-MA- (n=27), Younger HIV+MA- (n=33), and Younger HIV+MA+ (n=34). No participant met criteria for current MA use disorders and histories of MA dependence were remote in both the Older (average of nearly 9 years prior to evaluation) and Younger (average of over 2 years prior to evaluation) HIV+MA+ groups. Findings revealed that a remote history of MA dependence exerts a significant detrimental impact on specific aspects of neurocognitive performance (e.g., memory) and a broad range of real-world functioning outcomes (e.g., employment) among Older, but not Younger PLWH. These results suggest that MA-associated neurotoxicity may have significant “legacy” effects on both neurocognitive and functional outcomes to which older PLWH are particularly vulnerable. PMID:24470237

  14. 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.

  15. 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…

  16. 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

  17. Hypothalamic-pituitary-adrenal axis responses to stress in subjects with 3,4-methylenedioxy-methamphetamine ('ecstasy') use history: correlation with dopamine receptor sensitivity.

    PubMed

    Gerra, Gilberto; Bassignana, Sara; Zaimovic, Amir; Moi, Gabriele; Bussandri, Monica; Caccavari, Rocco; Brambilla, Francesca; Molina, Enzo

    2003-09-30

    Fifteen 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') users who did not have other drug dependencies or prolonged alcohol abuse and 15 control subjects were studied. All the subjects were exposed to the same psychosocial stressor (Stroop Color-Word Interference Task, public speaking and mental arithmetic in front of an audience) 3 weeks after MDMA discontinuation. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were measured immediately before the tests began and at their end, 30 min later. Growth hormone (GH) responses to the dopaminergic agonist bromocriptine and psychometric measures (Tridimensional Personality Questionnaire, Minnesota Multiphasic Personality Inventory, Buss-Durkee Hostility Inventory) were also obtained 4 weeks after MDMA discontinuation for the same subjects. ACTH and cortisol basal levels were significantly higher in ecstasy users than in control subjects. In contrast, ACTH and cortisol responses to stress were significantly blunted in MDMA users. The sensitivity of dopamine D2 receptors, reflected by GH responses to bromocriptine challenge, was reduced in MDMA users compared with controls. The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and cortisol delta peaks) correlated directly with GH areas under curves in response to bromocriptine, and inversely with psychometric measures of aggressiveness and novelty seeking. No correlation was found between hormonal measures and the extent of MDMA exposure. Reduced D2 receptor sensitivity, HPA basal hyperactivation and reduced responsiveness to stress may represent a complex neuroendocrine dysfunction associated with MDMA use. The present findings do not exclude the possibility that dopamine dysfunction partly predated MDMA exposure.

  18. 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

  19. Mind Over Matter: Methamphetamine

    MedlinePlus

    ... things, including inability to sleep, paranoia, aggressiveness, and hallucinations. The Brain's Response to Methamphetamine Hi, my name's ... things, including inability to sleep, paranoia, aggressiveness, and hallucinations. I'll tell you more about these later. ...

  20. Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression.

    PubMed

    Jiang, Mingjin; Chen, Yifei; Li, Chan; Peng, Qiuxian; Fang, Miao; Liu, Wei; Kang, Qunzhao; Lin, Yingbo; Yung, Ken Kin Lam; Mo, Zhixian

    2016-07-04

    Others and we have reported that rhynchophylline reverses amphetamine-induced conditioned place preference (CPP) effect which may be partly mediated by amelioration of central neurotransmitters and N-methyl-d-aspartate receptor 2B (NR2B) levels in the rat brains. The current study investigated the inhibiting effects of rhynchophylline on methamphetamine-induced (METH-induced) CPP in adult zebrafish and METH-induced locomotor activity in tyrosine hydroxylase-green fluorescent protein (TH-GFP) transgenic zebrafish larvae and attempted to confirm the hypothesis that these effects were mediated via regulation of neurotransmitters and dopaminergic and glutamatergic systems. After baseline preference test (on days 1-3), zebrafish were injected intraperitoneally METH (on days 4, 6 and 8) or the same volume of fish physiological saline (on days 5 and 7) and were immediately conditioned. Rhynchophylline was administered at 12h after injection of METH. On day 9, zebrafish were tested for METH-induced CPP. Results revealed that rhynchophylline (100mg/kg) significantly inhibited the acquisition of METH-induced CPP, reduced the content of dopamine and glutamate and down-regulated the expression of TH and NR2B in the CPP zebrafish brains. Furthermore, the influence of rhynchophylline on METH-induced locomotor activity was also observed in TH-GFP transgenic zebrafish larvae. Results showed that rhynchophylline (50mg/L) treatment led to a significant reduction on the locomotor activity and TH expression in TH-GFP transgenic zebrafish larvae. Taken together, these data indicate that the inhibition of the formation of METH dependence by rhynchophylline in zebrafish is associated with amelioration of the neurotransmitters dopamine and glutamate content and down-regulation of TH and NR2B expression.

  1. 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 ...

  2. Naltrexone and bupropion, alone or combined, do not alter the reinforcing effects of intranasal methamphetamine.

    PubMed

    Stoops, William W; Pike, Erika; Hays, Lon R; Glaser, Paul E; Rush, Craig R

    2015-02-01

    Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of good effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use.

  3. Naltrexone and Bupropion, Alone or Combined, Do Not Alter the Reinforcing Effects of Intranasal Methamphetamine

    PubMed Central

    Stoops, William W.; Pike, Erika; Hays, Lon R.; Glaser, Paul E.; Rush, Craig R.

    2014-01-01

    Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of Good Effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use. PMID:25459104

  4. 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.

  5. Neurobehavioral Effects from Developmental Methamphetamine Exposure.

    PubMed

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

    2016-01-01

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

  6. 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.

  7. 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

  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.

  9. Extinction-dependent alterations in corticostriatal mGluR2/3 and mGluR7 receptors following chronic methamphetamine self-administration in rats.

    PubMed

    Schwendt, Marek; Reichel, Carmela M; See, Ronald E

    2012-01-01

    Methamphetamine (meth) is a highly addictive and widely abused psychostimulant. Repeated use of meth can quickly lead to dependence, and may be accompanied by a variety of persistent psychiatric symptoms and cognitive impairments. The neuroadaptations underlying motivational and cognitive deficits produced by chronic meth intake remain poorly understood. Altered glutamate neurotransmission within the prefrontal cortex (PFC) and striatum has been linked to both persistent drug-seeking and cognitive dysfunction. Therefore, the current study investigated changes in presynaptic mGluR receptors within corticostriatal circuitry after extended meth self-administration. Rats self-administered meth (or received yoked-saline) in 1 hr/day sessions for 7 days (short-access) followed by 14 days of 6 hrs/day (long-access). Rats displayed a progressive escalation of daily meth intake up to 6 mg/kg per day. After cessation of meth self-administration, rats underwent daily extinction or abstinence without extinction training for 14 days before being euthanized. Synaptosomes from the medial PFC, nucleus accumbens (NAc), and the dorsal striatum (dSTR) were isolated and labeled with membrane-impermeable biotin in order to measure surface mGluR2/3 and mGluR7 receptors. Extended access to meth self-administration followed by abstinence decreased surface and total levels of mGluR2/3 receptors in the NAc and dSTR, while in the PFC, only a loss of surface mGluR2/3 and mGluR7 receptors was detected. Daily extinction trials reversed the downregulation of mGluR2/3 receptors in the NAc and dSTR and mGluR7 in the PFC, but downregulation of surface mGluR2/3 receptors in the PFC was present regardless of post-meth experience. Thus, extinction learning can selectively restore some populations of downregulated mGluRs after prolonged exposure to meth. The present findings could have implications for our understanding of the persistence (or recovery) of meth-induced motivational and cognitive

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

    ERIC Educational Resources Information Center

    Beaudreault, Amy R.

    2013-01-01

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

  11. Subjective experience of difficulty depends on multiple cues

    PubMed Central

    Desender, Kobe; Van Opstal, Filip; Van den Bussche, Eva

    2017-01-01

    Human cognition is characterized by subjective experiences that go along with our actions, but the nature and stability of these experiences remain largely unclear. In the current report, the subjective experience of difficulty is studied and it is proposed that this experience is constructed by integrating information from multiple cues. Such an account can explain the tight relationship between primary task performance and subjective difficulty, while allowing for dissociations between both to occur. Confirming this hypothesis, response conflict, reaction time and response repetition were identified as variables that contribute to the experience of difficulty. Trials that were congruent, fast or required the same response as the previous trial were more frequently rated as easy than trials that were incongruent, slow or required a different response as the previous trial. Furthermore, in line with theoretical accounts that relate metacognition to learning, a three day training procedure showed that the influence of these variables on subjective difficulty judgments can be changed. Results of the current study are discussed in relation to work on meta-memory and to recent theoretical advancements in the understanding of subjective confidence. PMID:28287137

  12. METHAMPHETAMINE SELF-ADMINISTRATION IN HUMANS DURING D-AMPHETAMINE MAINTENANCE

    PubMed Central

    Pike, Erika; Stoops, William W.; Hays, Lon R.; Glaser, Paul E. A.; Rush, Craig R.

    2014-01-01

    Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted d-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested two d-amphetamine maintenance conditions in counter-balanced order (0 and 40 mg/day). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled one of four doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug-effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 13 items of the drug-effects questionnaires, 10 of which were attenuated by d-amphetamine maintenance (e.g., increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by d-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during d-amphetamine maintenance and no adverse events occurred. Although d-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that d-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders. PMID:25154010

  13. Excess of autorefraction over subjective refraction: dependence on age.

    PubMed

    Joubert, L; Harris, W F

    1997-06-01

    The purpose of this study was to examine the difference between subjective refraction and autorefraction for different age groups. We call the difference (autorefraction minus subjective refraction) the excess of autorefraction over subjective refraction or the autorefractive excess. Five age groups of 50 subjects each were used. Subjects in group 1 were aged between 1 and 10 years, group 2 between 11 and 20 years, group 3 between 21 and 30 years, group 4 between 31 and 40 years, and group 5 consisted of subjects over 41 years of age. Automatic refraction was performed with an Allergan Humphrey model 580 autorefractor. The data were analyzed using recently developed statistical methods for the analyzing of dioptric power. These methods include the use of the coordinate vector h as a representation of dioptric power. The results indicate that there is a statistically significant mean autorefractive excess and that the mean is different for different age groups. The behavior of the left and right eyes appears to be essentially the same. In terms of vector h the mean autorefractive excess for both the left and the right eyes of group 1 (1 to 10 years of age) is approximately (-0.25 0.00-0.43)'. It increases by roughly delta h = (0.10 0.00 0.10)' per decade. In more conventional terms the nearest equivalent sphere of the mean excess for group 1 is approximately -0.34 D for the right and for the left eyes. The mean autorefractive excess for group 1 is approximately -0.25 -0.18 x 180. The astigmatic component appears to be the same for all age groups, whereas the spherical component increases by approximately 0.1 D per decade. The standard deviations of the autorefractive excesses are relatively large for components h1, and h3 of h: they were between approximately 0.4 and 0.7 D, possibly decreasing slightly with age. The standard deviation of h2 remains at 0.2 D or less for all age groups. The greatest variation of autorefractive excess appears to be approximately in the

  14. 5-HT(1A)-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians.

    PubMed

    Rawls, Scott M; Shah, Hardik; Ayoub, George; Raffa, Robert B

    2010-10-29

    No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 μM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal) than either methamphetamine-naïve planarians tested in water or methamphetamine-exposed planarians tested in methamphetamine. A concentration-related inhibition of withdrawal was observed when methamphetamine-exposed planarians were placed into a solution containing either methamphetamine and 5-HT (0.1-100 μM) or methamphetamine and the 5-HT(1A) receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) (10, 20 μM). Planarians with prior methamphetamine exposure displayed enhanced withdrawal when tested in a solution of the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) (1 μM). Methamphetamine-induced withdrawal was not affected by the 5-HT(2B/2C) receptor agonist meta-chlorophenylpiperazine (m-CPZ) (0.1-20 μM). These results provide pharmacological evidence that serotonin-enhancing drugs inhibit expression of methamphetamine physical dependence in an invertebrate model of withdrawal, possibly through a 5-HT(1A)-like receptor-dependent mechanism.

  15. 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.

  16. Methamphetamine affects cell proliferation in the medial prefrontal cortex: a new niche for toxicity.

    PubMed

    Kim, Airee; Mandyam, Chitra D

    2014-11-01

    Methamphetamine addicts demonstrate impaired frontal cortical-dependent cognitive function that could result from methamphetamine-induced maladaptive plasticity in the prefrontal cortex. Reduced adult gliogenesis observed in a rodent model of compulsive methamphetamine self-administration could contribute to the maladaptive plasticity in the medial prefrontal cortex (mPFC) as excessive methamphetamine intake is associated with loss of gliogenesis. The present study explored the vulnerability of mPFC progenitors to the duration of various sessions of methamphetamine self-administration in limited and extended access schedule of reinforcement. Proliferation of progenitors via Ki-67 labeling and apoptosis via activated caspase-3 labeling were studied in rats that intravenously self-administered methamphetamine in a limited access (1h/day: short access (ShA)) or extended access (6h/day: long access (LgA)) paradigm over 4, 13, 22 or 42 sessions, and in rats that experienced 22 sessions and were withdrawn from self-administration for a period of 4weeks. Four sessions of LgA methamphetamine enhanced proliferation and apoptosis and forty-two sessions of ShA and LgA methamphetamine reduced proliferation without effecting apoptosis. Withdrawal from twenty-two sessions of methamphetamine enhanced proliferation in LgA animals. Our findings demonstrate that proliferation of mPFC progenitors is vulnerable to psychostimulant exposure and withdrawal with distinct underlying mechanisms relating to methamphetamine toxicity. The susceptibility of mPFC progenitors to even modest doses of methamphetamine could account for the pronounced neuroadaptation in the mPFC linked to methamphetamine abuse.

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

    PubMed Central

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

    2012-01-01

    Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4×5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2×90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum. PMID:23056363

  18. Intracellular methamphetamine prevents the dopamine-induced enhancement of neuronal firing.

    PubMed

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

    2014-08-08

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

  19. Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure.

    PubMed

    Roussotte, Florence F; Rudie, Jeffrey D; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Narr, Katherine L; Sowell, Elizabeth R

    2012-01-01

    Various abnormalities in frontal and striatal regions have been reported in children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI study, we observed a correlation between accuracy on a working-memory task and functional activation in the putamen in children with prenatal methamphetamine and polydrug exposure. Because the putamen is part of the corticostriatal motor loop whereas the caudate is involved in the executive loop, we hypothesized that a loss of segregation between distinct corticostriatal networks may occur in these participants. The current study was designed to test this hypothesis using functional connectivity MRI. We examined 50 children ranging in age from 7 to 15, including 19 with prenatal methamphetamine exposure (15 of whom had concomitant prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not methamphetamine, and 18 unexposed controls. We measured the coupling between blood oxygenation level dependent (BOLD) fluctuations during a working-memory task in four striatal seed regions and those in the rest of the brain. We found that the putamen seeds showed increased connectivity with frontal brain regions involved in executive functions while the caudate seeds showed decreased connectivity with some of these regions in both groups of exposed subjects compared to controls. These findings suggest that localized brain abnormalities resulting from prenatal exposure to alcohol and/or methamphetamine lead to a partial rewiring of corticostriatal networks. These results represent important progress in the field, and could have substantial clinical significance in helping devise more targeted treatments and remediation strategies designed to better serve the needs of this population.

  20. Carrier-dependent and Ca2+-dependent 5-HT and dopamine release induced by (+)-amphetamine, 3,4-methylendioxy-methamphetamine, p-chloroamphetamine and (+)-fenfluramine

    PubMed Central

    Crespi, Daniela; Mennini, Tiziana; Gobbi, Marco

    1997-01-01

    The mechanism underlying 5-hydroxytryptamine (5-HT) and/or dopamine release induced by (+)-amphetamine ((+)-Amph), 3,4-methylendioxymethamphetamine (MDMA), p-chloroamphetamine (pCA) and (+)-fenfluramine ((+)-Fen) was investigated in rat brain superfused synaptosomes preloaded with the 3H neurotransmitters. Their rank order of potency for [3H]-5-HT-releasing activity was the same as for inhibition of 5-HT uptake (pCA⩾MDMA⩾(+)-Fen>>(+)-Amph). Similarly, their rank order as [3H]-dopamine releasers and dopamine uptake inhibitors was the same ((+)-Amph>>pCA=MDMA>>(+)-Fen). We also confirmed that the release induced by these compounds was prevented by selective transporter inhibitors (indalpine or nomifensine). [3H]-5-HT and/or [3H]-dopamine release induced by all these compounds was partially (31–80%), but significantly Ca2+-dependent. Lack of extracellular Ca2+ did not alter uptake mechanisms nor did it modify the carrier-dependent dopamine-induced [3H]-dopamine release. (+)-Amph-induced [3H]-dopamine release and pCA- and MDMA-induced [3H]-5-HT release were significantly inhibited by ω-agatoxin-IVA, a specific blocker of P-type voltage-operated Ca2+-channels, similar to the previous results on (+)-Fen-induced [3H]-5-HT release. Methiothepin inhibited the Ca2+-dependent component of (+)-Amph-induced [3H]-dopamine release with high potency (70 nM), as previously found with (+)-Fen-induced [3H]-5-HT release. The inhibitory effect of methiothepin was not due to its effects as a transporter inhibitor or Ca2+-channel blocker and is unlikely to be due to its antagonist properties on 5-HT1/2, dopamine or any other extracellular receptor. These results indicate that the release induced by these compounds is both ‘carrier-mediated' and Ca2+-dependent (possibly exocytotic-like), with the specific carrier allowing the amphetamines to enter the synaptosome. The Ca2+-dependent release is mediated by Ca2+-influx (mainly through P-type Ca2+-channels), possibly triggered by

  1. Frequency dependency of temporal contrast adaptation in normal subjects.

    PubMed

    Hohberger, Bettina; Rössler, Christopher W; Jünemann, Anselm G M; Horn, Folkert K; Kremers, Jan

    2011-06-21

    The aim of this study was to determine the influence of temporal frequency of temporal contrast adaptation on contrast sensitivity in healthy subjects. Temporal contrast sensitivities (TCS) were measured monocularly in seven healthy subjects with a modified ERG full-field bowl stimulator at eight different test temporal frequencies (9, 15, 20, 25, 31, 37, 44, 51 Hz) using a two-alternative-forced-choice strategy. Before each presentation of the test stimulus, a 100% contrast adapting flicker stimulus was presented (frequencies: 9, 15, 20, 25, 31, 37, 44, 51, 100 Hz). At each adapting frequency, a complete set of TCSs was measured. All temporal contrast sensitivities decreased with increasing temporal frequencies. Adaptation led to a general temporal contrast sensitivity decrease. Largest adaptation effects were seen at an adaptation frequency of 25 Hz. Reduction of contrast sensitivity was significantly larger at 25 Hz adaptation than at 9 Hz adaptation (t-test of paired samples, Bonferroni corrected). The results of this study showed a general TCS decrease with the largest effect at an adaptation frequency of 25 Hz. This finding indicates that the contrast adaptation probably occurred in the magnocellular-pathway. In future clinical studies adaptation effects could be investigated in patients with reduced temporal contrast sensitivity.

  2. Phosphodiesterase 1B differentially modulates the effects of methamphetamine on locomotor activity and spatial learning through DARPP32-dependent pathways: evidence from PDE1B-DARPP32 double-knockout mice.

    PubMed

    Ehrman, L A; Williams, M T; Schaefer, T L; Gudelsky, G A; Reed, T M; Fienberg, A A; Greengard, P; Vorhees, C V

    2006-10-01

    Mice lacking phosphodiesterase 1B (PDE1B) exhibit an exaggerated locomotor response to D-methamphetamine and increased in vitro phosphorylation of DARPP32 (dopamine- and cAMP-regulated phosphoprotein, M r 32 kDa) at Thr34 in striatal brain slices treated with the D1 receptor agonist, SKF81297. These results indicated a possible regulatory role for PDE1B in pathways involving DARPP32. Here, we generated PDE1B x DARPP32 double-knockout (double-KO) mice to test the role of PDE1B in DARPP32-dependent pathways in vivo. Analysis of the response to d-methamphetamine on locomotor activity showed that the hyperactivity experienced by PDE1B mutant mice was blocked in PDE1B-/- x DARPP32-/- double-KO mice, consistent with participation of PDE1B and DARPP32 in the same pathway. Further behavioral testing in the elevated zero-maze revealed that DARPP32-/- mice showed a less anxious phenotype that was nullified in double-mutant mice. In contrast, in the Morris water maze, double-KO mice showed deficits in spatial reversal learning not observed in either single mutant compared with wild-type mice. The data suggest a role for PDE1B in locomotor responses to psychostimulants through modulation of DARPP32-dependent pathways; however, this modulation does not necessarily impact other behaviors, such as anxiety or learning. Instead, the phenotype of double-KOs observed in these latter tasks may be mediated through independent pathways.

  3. A rodent "self-report" measure of methamphetamine craving? Rat ultrasonic vocalizations during methamphetamine self-administration, extinction, and reinstatement.

    PubMed

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

    2013-01-01

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

  4. Objective and subjective memory ratings in cannabis-dependent adolescents

    PubMed Central

    McClure, Erin A.; Lydiard, Jessica B.; Goddard, Scott D.; Gray, Kevin M.

    2015-01-01

    Background and Objectives Cannabis is the most widely used illicit substance worldwide, with an estimated 160 million users. Among adolescents, rates of cannabis use are increasing, while the perception of detrimental effects of cannabis use is declining. Difficulty with memory is one of the most frequently noted cognitive deficits associated with cannabis use, but little data exists exploring how well users can identify their own memory deficits, if present. Methods The current secondary analysis sought to characterize objective verbal and visual memory performance via a neurocognitive battery in cannabis-dependent adolescents enrolled in a pharmacotherapeutic cannabis cessation clinical trial (N=112) and compare this to a single self-reported item assessing difficulties with memory loss. Exploratory analyses also assessed dose-dependent effects of cannabis on memory performance. Results A small portion of the study sample (10%) endorsed a “serious problem” with memory loss. Those participants reporting “no problem” or “serious problem” scored similarly on visual and verbal memory tasks on the neurocognitive battery. Exploratory analyses suggested a potential relationship between days of cannabis use, amount of cannabis used, and gender with memory performance. Conclusions and Scientific Significance This preliminary and exploratory analysis suggests that a sub-set of cannabis users may not accurately perceive difficulties with memory. Further work should test this hypothesis with the use of a control group, comprehensive self-reports of memory problems, and adult populations that may have more years of cannabis use and more severe cognitive deficits. PMID:25823635

  5. Effects of maternal separation and methamphetamine exposure on protein expression in the nucleus accumbens shell and core.

    PubMed

    Dimatelis, J J; Russell, V A; Stein, D J; Daniels, W M

    2012-09-01

    Early life adversity has been suggested to predispose an individual to later drug abuse. The core and shell sub-regions of the nucleus accumbens are differentially affected by both stressors and methamphetamine. This study aimed to characterize and quantify methamphetamine-induced protein expression in the shell and core of the nucleus accumbens in animals exposed to maternal separation during early development. Isobaric tagging (iTRAQ) which enables simultaneous identification and quantification of peptides with tandem mass spectrometry (MS/MS) was used. We found that maternal separation altered more proteins involved in structure and redox regulation in the shell than in the core of the nucleus accumbens, and that maternal separation and methamphetamine had differential effects on signaling proteins in the shell and core. Compared to maternal separation or methamphetamine alone, the maternal separation/methamphetamine combination altered more proteins involved in energy metabolism, redox regulatory processes and neurotrophic proteins. Methamphetamine treatment of rats subjected to maternal separation caused a reduction of cytoskeletal proteins in the shell and altered cytoskeletal, signaling, energy metabolism and redox proteins in the core. Comparison of maternal separation/methamphetamine to methamphetamine alone resulted in decreased cytoskeletal proteins in both the shell and core and increased neurotrophic proteins in the core. This study confirms that both early life stress and methamphetamine differentially affect the shell and core of the nucleus accumbens and demonstrates that the combination of early life adversity and later methamphetamine use results in more proteins being affected in the nucleus accumbens than either treatment alone.

  6. 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.

  7. Complex role of zinc in methamphetamine toxicity in vitro.

    PubMed

    Aizenman, E; McCord, M C; Saadi, R A; Hartnett, K A; He, K

    2010-11-24

    Methamphetamine is a drug of abuse that can induce oxidative stress and neurotoxicity to dopaminergic neurons. We have previously reported that oxidative stress promotes the liberation of intracellular Zn(2+) from metal-binding proteins, which, in turn, can initiate neuronal injurious signaling processes. Here, we report that methamphetamine mobilizes Zn(2+) in catecholaminergic rat pheochromocytoma (PC12) cells, as measured by an increase in Zn(2+)-regulated gene expression driven by the metal response element transcription factor-1. Moreover, methamphetamine-liberated Zn(2+) was responsible for a pronounced enhancement in voltage-dependent K(+) currents in these cells, a process that normally accompanies Zn(2+)-dependent cell injury. Overnight exposure to methamphetamine induced PC12 cell death. This toxicity could be prevented by the cell-permeant zinc chelator N,N,N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), and by over-expression of the Zn(2+)-binding protein metallothionein 3 (MT3), but not by tricine, an extracellular Zn(2+) chelator. The toxicity of methamphetamine to PC12 cells was enhanced by the presence of co-cultured microglia. Remarkably, under these conditions, TPEN no longer protected but, in fact, dramatically exacerbated methamphetamine toxicity, tricine again being without effect. Over-expression of MT3 in PC12 cells did not mimic these toxicity-enhancing actions of TPEN, suggesting that the chelator affected microglial function. Interestingly, P2X receptor antagonists reversed the toxicity-enhancing effect of TPEN. As such, endogenous levels of intracellular Zn(2+) may normally interfere with the activation of P2X channels in microglia. We conclude that Zn(2+) plays a significant but complex role in modulating the cellular response of PC12 cells to methamphetamine exposure in both the absence and presence of microglia.

  8. 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

  9. Self-vaccination by methamphetamine glycation products chemically links chronic drug abuse and cardiovascular disease

    PubMed Central

    Treweek, Jennifer; Wee, Sunmee; Koob, George F.; Dickerson, Tobin J.; Janda, Kim D.

    2007-01-01

    Methamphetamine abuse is spreading rapidly throughout the United States and is characterized by significant health consequences. The powerfully rewarding effects of methamphetamine are attributed to multiple neuropharmacological actions such as its ability to block plasma membrane transporters of all monoamines, reduce dopamine transporter expression, and inhibit monoamine oxidase activity while increasing tyrosine hydroxylase activity. However, subsequent neuroreceptor changes including monoamine deficits complement this striking increase in monoamine release. Chronic methamphetamine abuse, as studied via self-administration paradigms in rodents, causes progressive dopaminergic neurotoxicity, a neuroanatomical change accompanied by increasing drug tolerance and escalating intake, two behavioral parameters of addiction. We have recently proposed that methamphetamine covalently glycates endogenous proteins. Such an event spurs antibody production against these immunoconjugates, possibly leading to drug sequestration by antibody binding of drug. Here we demonstrate that this drug-dependent glycation mechanism is operative in vivo through the dose-dependent detection of antibodies against methamphetamine-derived advanced glycation end products in rats chronically self-administering methamphetamine. Furthermore, increased levels of proinflammatory cytokines, evidence of potent immunoactivation, were also detected. Given the known role of advanced glycation end products in the alteration of protein function in vivo and the participation of these molecules in various diseases, methamphetamine-derived advanced glycation end products provide an unrecognized molecular mechanism for the development of vasculitis and other cardiovascular maladies reported with high incidence in chronic methamphetamine users. PMID:17592122

  10. Insanity, methamphetamine and psychiatric expertise in New Zealand courtrooms.

    PubMed

    Thom, Katey; Finlayson, Mary; McKenna, Brian

    2011-06-01

    The use of methamphetamine in New Zealand has increased significantly over the last decade. Due to the potential of methamphetamine to induce, exacerbate and precipitate psychotic symptoms, this drug has also taken centre stage in several criminal trials considering the sanity of defendants. Highly publicised and often involving contested expert evidence, these criminal trials have illustrated the limits of using psychiatric expertise to answer legal questions. This article considers the implications of such cases in light of material from a qualitative study that aimed to generate insights into the difficulties forensic psychiatrists and their instructing lawyers face when providing expert evidence on the relationship between methamphetamine, psychosis and insanity. It reports material from 31 in-depth interviews with lawyers and forensic psychiatrists and observation of one criminal trial that considered the relationship between methamphetamine and legal insanity. The findings are correlated with the clinical and medico-legal literature on the topic and subjected to scrutiny through the lens of "sanism". The article concludes that the continued use of forensic psychiatry to meet the legal objectives of insanity, where methamphetamine is involved, has the potential to reinforce sanist attitudes and practices.

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

    PubMed

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

    2015-05-01

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

  12. Primary health-care responses to methamphetamine use in Australian Indigenous communities.

    PubMed

    MacLean, Sarah; Harney, Angela; Arabena, Kerry

    2015-01-01

    Crystal methamphetamine (commonly known as 'ice') use is currently a deeply concerning problem for some Australian Indigenous peoples and can cause serious harms to individual, families and communities. This paper is intended to support best practice responses by primary health-care staff working with Australian Indigenous people who use methamphetamine. It draws on a systematic search of relevant databases to identify literature from January 1999 to February 2014, providing an overview of prevalence, treatment, education and harm reduction, and community responses. The prevalence of methamphetamine use is higher in Indigenous than non-Indigenous communities, particularly in urban and regional settings. No evidence was identified that specifically related to effective treatment and treatment outcomes for Indigenous Australians experiencing methamphetamine dependence or problematic use. While studies involving methamphetamine users in the mainstream population suggest that psychological and residential treatments show short-term promise, longer-term outcomes are less clear. Community-driven interventions involving Indigenous populations in Australia and internationally appear to have a high level of community acceptability; however, outcomes in terms of methamphetamine use are rarely evaluated. Improved national data on prevalence of methamphetamine use among Indigenous people and levels of treatment access would support service planning. We argue for the importance of a strength-based approach to addressing methamphetamine use, to counteract the stigma and despair that frequently accompanies it.

  13. 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.

  14. Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection?

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2011-01-01

    In the present study, light and electron microscopy were used to examine heat shock protein (HSP 72 kD) expression during acute methamphetamine (METH) intoxication in rats and evaluate its relationships with brain temperature and alterations in a number of other histochemical and morphological parameters. Freely moving rats received METH at the same dose (9 mg/kg, sc) but at different ambient temperatures (23 and 29°C), showing a wide range of brain temperature elevations (37.6-42.5°C); brains were taken for histochemical and morphological evaluations at peak of brain temperature increase. We found that acute METH intoxication induces massive and wide-spread HSP expression in neural and glial cells examined in detail in the cortex, hippocampus, thalamus, and hypothalamus. In each of these structures, the number of HSP-positive cells tightly correlated with brain temperature elevation. The changes in HSP immunoreactivity were also tightly related to alterations in permeability of the blood-brain barrier, acute glial activation, and brain edema assessed by albumin and GFAP immunoreactivity and measuring tissue water content, respectively. While robust and generalized HSP production normally appears to be the part of an adaptive brain response associated with METH-induced metabolic activation, activation of this protective mechanism has its natural limits and could not counteract the damaging effects of oxidative stress, high temperature, and edema--the leading factors of METH-induced neurotoxicity.

  15. Meth math: modeling temperature responses to methamphetamine.

    PubMed

    Molkov, Yaroslav I; Zaretskaia, Maria V; Zaretsky, Dmitry V

    2014-04-15

    Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants.

  16. Meth math: modeling temperature responses to methamphetamine

    PubMed Central

    Molkov, Yaroslav I.; Zaretskaia, Maria V.

    2014-01-01

    Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants. PMID:24500434

  17. Duration effects in contingency management treatment of methamphetamine disorders.

    PubMed

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

    2013-09-01

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

  18. Methamphetamine induces Shati/Nat8L expression in the mouse nucleus accumbens via CREB- and dopamine D1 receptor-dependent mechanism

    PubMed Central

    Uno, Kyosuke; Miyazaki, Toh; Sodeyama, Kengo; Miyamoto, Yoshiaki

    2017-01-01

    Shati/Nat8L significantly increased in the nucleus accumbens (NAc) of mice after repeated methamphetamine (METH) treatment. We reported that Shati/Nat8L overexpression in mouse NAc attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference. We recently found that Shati/Nat8L overexpression in NAc regulates the dopaminergic neuronal system via the activation of group II mGluRs by elevated N-acetylaspartylglutamate following N-acetylaspartate increase due to the overexpression. These findings suggest that Shati/Nat8L suppresses METH-induced responses. However, the mechanism by which METH increases the Shati/Nat8L mRNA expression in NAc is unclear. To investigate the regulatory mechanism of Shati/Nat8L mRNA expression, we performed a mouse Shati/Nat8L luciferase assay using PC12 cells. Next, we investigated the response of METH to Shati/Nat8L expression and CREB activity using mouse brain slices of NAc, METH administration to mice, and western blotting for CREB activity of specific dopamine receptor signals in vivo and ex vivo. We found that METH activates CREB binding to the Shati/Nat8L promoter to induce the Shati/Nat8L mRNA expression. Furthermore, the dopamine D1 receptor antagonist SCH23390, but not the dopamine D2 receptor antagonist sulpiride, inhibited the upregulation of Shati/Nat8L and CREB activities in the mouse NAc slices. Thus, the administration of the dopamine D1 receptor agonist SKF38393 increased the Shati/Nat8L mRNA expression in mouse NAc. These results showed that the Shati/Nat8L mRNA was increased by METH-induced CREB pathway via dopamine D1 receptor signaling in mouse NAc. These findings may contribute to development of a clinical tool for METH addiction. PMID:28319198

  19. The Effects of Levetiracetam on Alcohol Consumption in Alcohol-Dependent Subjects: An Open Label Study

    PubMed Central

    Sarid-Segal, Ofra; Piechniczek-Buczek, Joanna; Knapp, Clifford; Afshar, Maryam; Devine, Eric; Sickles, Laurie; Uwodukunda, Emma; Richambault, Courtney; Koplow, Jillian; Ciraulo, Domenic

    2017-01-01

    The aim of this open-label pilot study was to assess the efficacy and safety of the novel anticonvulsant agent, levetiracetam, for the treatment of alcohol dependence. A maximal dose of 2000 mg was administered daily for 10 weeks to alcohol dependent subjects (n = 20). Mean reported ethanol intake declined significantly from 5.3 to 1.7 standard drinks per day. Levetiracetam was well tolerated by most subjects. PMID:18584574

  20. Methamphetamine Lab Incidents, 2004-2014

    MedlinePlus

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

  1. Neurocognitive deficits are associated with unemployment in chronic methamphetamine users

    PubMed Central

    Weber, Erica; Blackstone, Kaitlin; Iudicello, Jennfer E.; Morgan, Erin E.; Grant, Igor; Moore, David J.; Woods, Steven Paul

    2013-01-01

    Background Unemployment rates are high among chronic methamphetamine (MA) users and carry a significant economic burden, yet little is known about the neurocognitive and psychiatric predictors of employment in this vulnerable population. Methods The present study examined this issue in 63 participants with recent MA dependence and 47 comparison subjects without histories of MA use disorders. All participants completed a comprehensive neurocognitive, psychiatric and neuromedical evaluation. Individuals with HIV infection, severe neuropsychological or psychiatric conditions that might affect cognition (e.g., seizure disorder, schizophrenia), or a positive Breathalyzer or urine toxicology screen on the day of testing were excluded. Results Consistent with previous research, a logistic regression revealed MA dependence as a significant, independent predictor of full-time unemployment status. Within the MA-dependent sample, greater impairment in global neurocognitive functioning and history of injection drug use emerged as significant independent predictors of unemployment status. The association between worse global cognitive functioning and unemployment was primarily driven by deficits in executive functions, learning, verbal fluency, and working memory. Conclusion These findings indicate that neurocognitive deficits play a significant role in the higher unemployment rates of MA-dependent individuals, and highlight the need for vocational rehabilitation and supported employment programs that assess and bolster cognitive skills in this population. PMID:22560676

  2. Impaired reproduction of three-dimensional objects by cocaine-dependent subjects.

    PubMed

    Elman, Igor; Chi, Won H; Gurvits, Tamara V; Ryan, Elizabeth T; Lasko, Natasha B; Lukas, Scott E; Pitman, Roger K

    2008-01-01

    This study employed a perceptual-motor task of figure copying in 27 cocaine-dependent, 26 marijuana-abusing or dependent, and 33 healthy subjects. Cocaine-dependent and healthy individuals did not differ in their scores on the copying of a two-dimensional diamond and a cross. In contrast, cocaine-dependent subjects displayed significantly poorer ability to copy a three-dimensional Necker cube, a smoking pipe, a hidden line elimination cube, a pyramid, and a dissected pyramid. Marijuana users' performance on all copied figures was comparable to that of the healthy comparison subjects. Considering that decreased three-dimensional copying ability has been found to be associated with fatal injuries, further studies are needed to investigate possible underlying mechanisms (e.g., parietal lobe damage) and their role in the pathophysiology of cocaine dependence.

  3. Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse treatment

    PubMed Central

    Brensilver, Matthew; Heinzerling, Keith G.; Swanson, Aimee-Noelle; Telesca, Donatello; Furst, Benjamin A.; Shoptaw, Steven J.

    2012-01-01

    Introduction and Aims Cigarette smoking occurs frequently among individuals with methamphetamine dependence. Preclinical and clinical evidence has suggested that the common co-abuse of methamphetamine and cigarettes represents a pharmacologically meaningful pattern. Methods The present study is a secondary analysis of a randomised, placebo-controlled trial of bupropion treatment for methamphetamine dependence (bupropion n=36; placebo n=37). A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non-smokers. Among smokers, relations between cigarettes smoked and MA use were assessed. Results Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition. In the placebo condition, increased cigarette use was associated with an increased probability of methamphetamine use during the same time period. This effect was not observed in the bupropion condition. Discussion and Conclusions Initial smoking status did not impact treatment outcomes. Among smokers, results suggest that bupropion may dissociate cigarette and methamphetamine use. The effect was modest and a precise pharmacologic mechanism remains elusive. Cholinergic systems may be relevant for methamphetamine use outcomes. Future studies should continue to assess the role of smoking in methamphetamine treatment outcomes. PMID:22385210

  4. 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…

  5. Deposition characteristics of methamphetamine and amphetamine in fingernail clippings and hair sections.

    PubMed

    Lin, Dong-Liang; Yin, Rea-Ming; Liu, Hsiu-Chuan; Wang, Chung-Yi; Liu, Ray H

    2004-09-01

    Fingernail clippings collected from 97 consenting females, who admitted amphetamines and/or opiates use and are currently under treatment, were quantitatively analyzed for the presence of methamphetamine and amphetamine. Sixty-two subjects were found positive for methamphetamine/amphetamine. Paired nail-hair specimens were collected from 6 of these subjects for a 12-week period and analyzed to determine the duration of detectability and deposition characteristics of amphetamines in fingernails; whether data derived from the analysis of nail clippings and hair sections are reflective of drug use patterns; and whether there is a relationship between the analytical data derived from the paired nail-hair specimens. Typical sample pre-treatment procedures and GC-MS protocols were evaluated to establish the validity of various analytical parameters and to ensure that the resulting data can be properly interpreted. Major findings include 1. Methamphetamine was found in the nails of 62 subjects collected in Week 0. The distribution of methamphetamine concentrations (ng/mg) in these nail samples are range, 0.46-61.50; mean, 9.96; and standard deviation: 13.33. The corresponding data for amphetamine are < 0.20-5.42, 0.93, and 1.01, respectively. 2. Sectional analyses of hair samples collected from 6 subjects in Week 0 show methamphetamine concentrations peak at different distances from the root. 3. The concentrations of methamphetamine and amphetamine in nail clippings are generally lower than the first 1.5-cm section of hair samples collected at the same time from the same individual. 4. Amphetamine/ methamphetamine concentration ratios in nail clippings and hair samples are comparable. 5. Methamphetamine concentration in the nail clippings collected at Weeks 0, 4, 8, and 12 decreases in a pattern similar to that exhibited by the first 1.5-cm sections of the hair samples collected at the same time.

  6. Volume reductions in frontopolar and left perisylvian cortices in methamphetamine induced psychosis.

    PubMed

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

    2013-07-01

    Consumption of methamphetamine disturbs dopaminergic transmission and sometimes provokes schizophrenia-like-psychosis, named methamphetamine-associated psychosis (MAP). While previous studies have repeatedly reported regional volume reductions in the frontal and temporal areas as neuroanatomical substrates for psychotic symptoms, no study has examined whether such neuroanatomical substrates exist or not in patients with MAP. Magnetic resonance images obtained from twenty patients with MAP and 20 demographically-matched healthy controls (HC) were processed for voxel-based morphometry (VBM) using Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra. An analysis of covariance model was adopted to identify volume differences between subjects with MAP and HC, treating intracranial volume as a confounding covariate. The VBM analyses showed significant gray matter volume reductions in the left perisylvian structures, such as the posterior inferior frontal gyrus and the anterior superior temporal gyrus, and the frontopolar cortices, including its dorsomedial, ventromedial, dorsolateral, and ventrolateral portions, and white matter volume reduction in the orbitofrontal area in the patients with MAP compared with the HC subjects. The smaller regional gray matter volume in the medial portion of the frontopolar cortex was significantly correlated with the severe positive symptoms in the individuals with MAP. The volume reductions in the left perisylvian structure suggest that patients with MAP have a similar pathophysiology to schizophrenia, whereas those in the frontopolar cortices and orbitofrontal area suggest an association with antisocial traits or vulnerability to substance dependence.

  7. Reduced Prefrontal Cortex Hemodynamic Response in Adults with Methamphetamine Induced Psychosis: Relevance for Impulsivity

    PubMed Central

    Yamamuro, Kazuhiko; Kimoto, Sohei; Iida, Junzo; Kishimoto, Naoko; Nakanishi, Yoko; Tanaka, Shohei; Ota, Toyosaku; Makinodan, Manabu; Kishimoto, Toshifumi

    2016-01-01

    Patients with methamphetamine abuse/dependence often exhibit high levels of impulsivity, which may be associated with the structural abnormalities and functional hypoactivities observed in the frontal cortex of these subjects. Although near-infrared spectroscopy (NIRS) is a simple and non-invasive method for characterizing the clinical features of various psychiatric illnesses, few studies have used NIRS to directly investigate the association between prefrontal cortical activity and inhibitory control in patients with methamphetamine-induced psychosis (MAP). Using a 24-channel NIRS system, we compared hemodynamic responses during the Stroop color-word task in 14 patients with MAP and 21 healthy controls matched for age, sex and premorbid IQ. In addition, we used the Barrett Impulsivity Scale-11 (BIS-11) to assess impulsivity between subject groups. The MAP group exhibited significantly less activation in the anterior and frontopolar prefrontal cortex accompanied by lower Stroop color-word task performance, compared with controls. Moreover, BIS-11 scores were significantly higher in the MAP group, and were negatively correlated with the hemodynamic responses in prefrontal cortex. Our data suggest that reduced hemodynamic responses in the prefrontal cortex might reflect higher levels of impulsivity in patients with MAP, providing new insights into disrupted inhibitory control observed in MAP. PMID:27050450

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Effects of Self-Administered Methamphetamine on Discrimination Learning and Reversal in Nonhuman Primates

    PubMed Central

    Kangas, Brian D.; Bergman, Jack

    2015-01-01

    Rationale Frequent exposure to methamphetamine has been reported to adversely influence cognitive behavior and, in particular, inhibitory control processes. Objective The present studies were conducted in squirrel monkeys to assess the effects of daily intravenous methamphetamine self-administration on touchscreen-based repeated acquisition and discrimination reversal tasks thought to reflect behavioral dimensions of, respectively, learning and response inhibition. Methods First, stable methamphetamine-maintained behavior was established (0.35-1.6 mg/kg/session) and, subsequently, a second daily session of discrimination learning was conducted (20 hr later). Subjects first learned to discriminate between two simultaneously presented stimuli (acquisition) and, subsequently, to re-learn the discrimination with the contingencies switched (reversal). The role of the interval between self-administration and touchscreen sessions was evaluated, as well as the effects of abrupt methamphetamine discontinuation. Results Results indicate that daily methamphetamine self-administration markedly disrupted the development of discrimination learning, initially requiring nearly twice the number of trials to master discriminations. The magnitude of adverse effects in individual subjects correlated to the level of daily methamphetamine intake. Importantly, however, behavioral disruption of discrimination learning was surmounted following remedial training. Once criterion levels of discrimination performance were achieved, subsequent development of reversal performance was largely unaffected except when the interval between self-administration and touchscreen session was short and, thus, likely vulnerable to methamphetamine’s direct effects. Discontinuation of methamphetamine produced no disruption in acquisition or reversal. Conclusion These results indicate that self-administered methamphetamine can markedly disrupt learning processes and, as well, highlights key differences in

  15. 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.

  16. 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

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

    PubMed

    Dew, Brian J

    2010-05-14

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

  18. The development of antibody-based immunotherapy for methamphetamine abuse: immunization, and virus-mediated gene transfer approaches.

    PubMed

    Chen, Yun-Hsiang; Chen, Chia-Hsiang

    2013-02-01

    Methamphetamine is a highly addictive psychostimulant that has been seriously abused worldwide, and currently there are no approved medications for the treatment of its abuse. Conventional treatments for drug addiction mainly seek to use small molecule agonists or antagonists to target the drug receptors in the brain, but unfortunately it is difficult to find a similar small molecule for the treatment of methamphetamine dependence. Alternatively, anti-methamphetamine antibodies can sequester the drug in the bloodstream and reduce the amount of drug available to the central nervous system, acting as peripheral pharmacokinetic antagonists. This review describes the development of antibody-based immunotherapies, classified into active and passive immunizations, for the treatment of methamphetamine addiction. Furthermore, an alternative therapeutic approach, using a recombinant adeno-associated virus-mediated gene transfer technique to achieve in vivo expression of characterized anti-methamphetamine monoclonal antibodies, is proposed in this article.

  19. 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.

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

    PubMed

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

    2014-01-01

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

  1. Methamphetamine Inhibits HIV-1 Replication in CD4+ T Cells by Modulating Anti–HIV-1 miRNA Expression

    PubMed Central

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

    2015-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4+ T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4+ T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti–HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4+ T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. PMID:24434277

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

    PubMed

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

    2016-01-01

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

  3. 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.

  4. 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

  5. Methamphetamine-Associated Psychosis and Treatment With Haloperidol and Risperidone: A Pilot Study

    PubMed Central

    Samiei, Mercede; Vahidi, Mohammad; Rezaee, Omid; Yaraghchi, Azadeh; Daneshmand, Reza

    2016-01-01

    Background Different studies have suggested that antipsychotic medications of the first generation have better effectiveness for the treatment of psychotic symptoms compared with antipsychotic medications of the second generation. Objectives The current study was the first pilot study in Iran that compared Haloperidol with Risperidone in the treatment of positive symptoms of psychosis among a group of methamphetamine-dependent patients. Materials and Methods This randomized clinical trial was designed and conducted in 2012. Overall, 44 patients who met the diagnostic and statistical manual of mental disorders, fourth edition-text revised (DSM.IV-TR) criteria for methamphetamine-associated psychosis (MAP) and were hospitalized at Razi psychiatric hospital in Tehran were selected. Patients (1: 1) were randomly divided to two groups. Overall, 22 subjects received Haloperidol (5 - 20 mg) and 22 subjects received Risperidone (2 - 8 mg). All subjects were assessed at baseline, during three consecutive weeks of treatment and one week after treatment (i.e., follow-up). Scale of assessment of positive symptoms (SAPS) was completed for each subject. Results The study findings indicated that both Haloperidol (< 0.05) and Risperidone (< 0.05) were similarly applicable in the treatment of MAP but no differential effectiveness was found between the two medications. The treatment effects of both medications increased in the first two weeks of treatment and remained stable in the second two weeks. Conclusions Risperidone and Haloperidol are two effective antipsychotic medications for the treatment of positive symptoms of MAP but other aspects of these two neuroleptic medications such as the long-term treatment effects should be studied. Further studies with more samples and longer follow-ups are suggested. PMID:27822286

  6. 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.

  7. Ubiquitin-immunoreactive structures in the midbrain of methamphetamine abusers.

    PubMed

    Quan, Li; Ishikawa, Takaki; Michiue, Tomomi; Li, Dong-Ri; Zhao, Dong; Oritani, Shigeki; Zhu, Bao-Li; Maeda, Hitoshi

    2005-05-01

    Ubiquitin (Ub) is involved in neurodegeneration and various stress responses in the brain. The present study investigated the Ub-immunoreactive structures in the midbrain of methamphetamine (MA) abusers as a marker of drug-induced neurodegeneration. Medico-legal autopsy cases were examined: fatal MA intoxication (n=14), other fatalities of MA abusers (n=23) including those due to injuries, asphyxiation, drowning, fire and natural diseases, and control groups (n=260). In the motor nervous systems, MA abusers showed a mild increase in the diffuse-type nuclear Ub-positivity in the pigmented neurons of the substantia nigra, depending on the blood MA level and irrespectively of the immediate causes of death. The intranuclear inclusion-type Ub-positivity of the nigral neurons and the granular 'dot-like' Ub-immunoreactivity area in the crus cerebri (cortico-spinal tracts) were usually low in MA abusers, and any increases were related to the immediate causes of death and the age of subjects. Acute MA fatality showed a higher neuronal Ub-positivity in the midbrain periaqueductal gray matter (PGM), which is involved in processing pain, fear and anxiety, and regulation of respiration and circulation. These findings suggest dysfunction of the nigral dopaminergic neurons and PGM neurons in the midbrain in MA abuse, which may account for the clinical symptoms.

  8. Implications of chronic methamphetamine use: a literature review.

    PubMed

    Meredith, Charles W; Jaffe, Craig; Ang-Lee, Kathleen; Saxon, Andrew J

    2005-01-01

    Methamphetamine (MA) abuse is increasing to epidemic proportions, both nationally and globally. Chronic MA use has been linked to significant impairments in different arenas of neuropsychological function. To better understand this issue, a computerized literature search (PubMed, 1964-2004) was used to collect research studies examining the neurobiological and neuropsychiatric consequences of chronic MA use. Availability of MA has markedly increased in the United States due to recent technological improvements in both mass production and clandestine synthesis, leading to significant public health, legal, and environmental problems. MA intoxication has been associated with significant psychiatric and medical comorbidity. Research in animal models and human subjects reveals complicated mechanisms of neurotoxicity by which chronic MA use affects catecholamine neurotransmission. This pathology may underlie the characteristic cognitive deficits that plague chronic MA users, who experience impairments in memory and learning, psychomotor speed, and information processing. These impairments have the potential to compromise, in turn, the ability of MA abusers to engage in, and benefit from, psychosocially based chemical-dependency treatment. Development of pharmacological interventions to improve these cognitive impairments in this population may significantly improve the degree to which they may be able to participate in treatment. Atypical antipsychotics may have some promise in this regard.

  9. Aeroelastic response of an aircraft wing with mounted engine subjected to time-dependent thrust

    NASA Astrophysics Data System (ADS)

    Mazidi, A.; Kalantari, H.; Fazelzadeh, S. A.

    2013-05-01

    In this paper, the aeroelastic response of a wing containing an engine subjected to different types of time-dependent thrust excitations is presented. In order to precisely consider the spanwise and chordwise locations of the engine and the time-dependent follower force in governing equations, derived through Lagrange's method, the generalized function theory is used. Unsteady aerodynamic lift and moment in the time domain are considered in terms of Wagner's function. Numerical simulations of the aeroelastic response to different types of time-dependent thrust excitation and comparisons with the previously published results are supplied. Effects of the engine mass and location and also the type of time-dependent thrust on the wing aeroelastic response are studied and pertinent conclusions are outlined.

  10. Temperament and character inventory dimensions and anhedonia in detoxified substance-dependent subjects.

    PubMed

    Martinotti, G; Cloninger, C R; Janiri, L

    2008-01-01

    In this study we aimed to investigate the relationship between anhedonia, craving and temperament and character dimensions in a sample of 50 patients with alcohol and opiate dependence recruited after a period of detoxification. The following scales were applied: Snaith-Hamilton Pleasure Scale (SHAPS), Bech-Rafaelsen Melancholia Scale (BRMS), Scale for the Assessment of Negative Symptoms (SANS), Visual Analogue Scales (VAS) for craving, and Temperament and Character Inventory (TCI). The temperament dimension of Novelty Seeking was positively correlated to craving and anhedonia (p < .01), with a higher score of Novelty Seeking in the subsample of anhedonic subjects with respect to both non-anhedonic and control subjects. In our study, the possibility that difficulty in experiencing pleasure in psychiatric disorders can lead to the use of psychoactive substances in an attempt to decrease anhedonia, is extended to subjects without psychiatric disorders who may try substances to counterbalance a tonic state of anhedonia.

  11. 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.

  12. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Insomnia in Alcohol Dependent Subjects is Associated with Greater Psychosocial Problem Severity

    PubMed Central

    Chaudhary, Ninad S.; Kampman, Kyle M.; Kranzler, Henry R.; Grandner, Michael A.; Debbarma, Swarnalata; Chakravorty, Subhajit

    2015-01-01

    Introduction Although psychosocial problems are commonly associated with both alcohol misuse and insomnia, very little is known about the combined effects of insomnia and current alcohol dependence on the severity of psychosocial problems. The present study evaluates whether the co-occurrence of insomnia and alcohol dependence is associated with greater psychosocial problem severity. Methods Alcohol dependent individuals (N=123) were evaluated prior to participation in a placebo-controlled medication trial. The Short Index of Problems (SIP), Addiction Severity Index (ASI), Insomnia Severity Index (ISI), and Time Line Follow Back (TLFB), were used to assess psychosocial, employment, and legal problems; insomnia symptoms; and alcohol consumption, respectively. Bivariate and multivariate analyses were used to evaluate the relations between insomnia and psychosocial problems. Results Subjects’ mean age was 44 years (SD=10.3), 83% were male, and their SIP sub-scale scores approximated the median for normative data. A quarter of subjects reported no insomnia; 29% reported mild insomnia; and 45% reported moderate-severe insomnia. The insomnia groups did not differ on alcohol consumption measures. The ISI total score was associated with the SIP total scale score (β=0.23, p=0.008). Subjects with moderate-severe insomnia had significantly higher scores on the SIP total score, and on the social and impulse control sub-scales, and more ASI employment problems and conflicts with their spouses than others on the ASI. Conclusion In treatment-seeking alcohol dependent subjects, insomnia may increase alcohol-related adverse psychosocial consequences. Longitudinal studies are needed to clarify the relations between insomnia and psychosocial problems in these subjects. PMID:26151580

  16. Optical study on the dependence of breast tissue composition and structure on subject anamnesis

    NASA Astrophysics Data System (ADS)

    Taroni, Paola; Quarto, Giovanna; Pifferi, Antonio; Abbate, Francesca; Balestreri, Nicola; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo

    2015-07-01

    Time domain multi-wavelength (635 to 1060 nm) optical mammography was performed on 200 subjects to estimate their average breast tissue composition in terms of oxy- and deoxy-hemoglobin, water, lipid and collagen, and structural information, as provided by scattering parameters (amplitude and power). Significant (and often marked) dependence of tissue composition and structure on age, menopausal status, body mass index, and use of oral contraceptives was demonstrated.

  17. Neural correlates of impulsive aggressive behavior in subjects with a history of alcohol dependence.

    PubMed

    Kose, Samet; Steinberg, Joel L; Moeller, F Gerard; Gowin, Joshua L; Zuniga, Edward; Kamdar, Zahra N; Schmitz, Joy M; Lane, Scott D

    2015-04-01

    Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM-IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity.

  18. Neural Correlates of Impulsive Aggressive Behavior in Subjects With a History of Alcohol Dependence

    PubMed Central

    Kose, Samet; Steinberg, Joel L.; Moeller, F. Gerard; Gowin, Joshua L.; Zuniga, Edward; Kamdar, Zahra N.; Schmitz, Joy M.; Lane, Scott D.

    2015-01-01

    Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM–IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity. PMID:25664566

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

    PubMed

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

    2017-05-01

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

  20. 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

  1. 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.

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

    PubMed Central

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

    2015-01-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”), appears to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of two other “social” drugs on plasma oxytocin levels: methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin. In Study 1, 11 healthy adult volunteers attended three sessions during which they received methamphetamine (10mg or 20mg) or placebo under double blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin were measured at regular intervals throughout the sessions. In Study 2, 8 healthy adult volunteers attended a single session during which they received one beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither drug increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified. PMID:25853370

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. Gender-dependent reduction of spontaneous motor activity and growth in rats subjected to portacaval shunt.

    PubMed

    Conjeevaram, H S; Mullen, K D; May, E J; McCullough, A J

    1994-02-01

    Alterations in behavior are frequently described in rats subjected to portacaval shunt. Previous work has reported reduced spontaneous motor activity in various settings (nighttime, red light, decreased illumination) in this animal model. We investigated this phenomenon in rats of both genders subjected to portacaval shunt to determine whether our previously observed divergent growth patterns (males reduced, females unchanged) had any impact on the alterations in spontaneous motor activity in this model. Dietary intake, growth, motor activity and serum ammonia and amino acid concentrations were measured, in addition to final liver and spleen weights, in each animal after 3 to 4 wk of observation. Our results reconfirm the differential impact of portacaval shunt on growth in male (35% reduction p < 0.01) but not female rats (5% reduction, NS) compared with their respective-gender sham-operated controls. In addition, spontaneous motor activity was significantly reduced in male (congruent to 50%, p = 0.01) but not female rats subjected to portacaval shunt. The reduction of activity in male rats subjected to portacaval shunt did not correlate with any of the measured biochemical data or calculated nutritional/growth parameters. Thus we observed gender-dependent reduction in spontaneous motor activity after portacaval shunt in the rat. The mechanism for this phenomenon is unknown, but it is easily investigated with this reproducible model.

  10. 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.

  11. Cloninger's typology and treatment outcome in alcohol-dependent subjects during pharmacotherapy with naltrexone.

    PubMed

    Kiefer, Falk; Jiménez-Arriero, Miguel Angel; Klein, Oliver; Diehl, Alexander; Rubio, Gabriel

    2008-03-01

    Naltrexone is an opiate receptor antagonist mainly at the micro-receptor that is thought to reduce the positively reinforcing, pleasurable effects of alcohol and to reduce craving. An increase in time to first relapse to heavy drinking has been the most consistent finding obtained with naltrexone, although not all trials including two of the largest have been positive. Inconsistent outcome data suggest that effectiveness varies among different subgroups of patients. This paper re-evaluates recent data on the effectiveness of naltrexone in subjects differentiated according to Cloninger Type I and II. Moreover, it combines and cross-validates results of two recent European studies that found naltrexone treatment more beneficial in alcohol-dependent patients with early age at onset of drinking problems (Cloninger Type II). It is discussed whether especially these subjects should be targeted for pharmacological relapse prevention treatment with naltrexone.

  12. 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.

  13. 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…

  14. 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…

  15. 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.

  16. Treatments for methamphetamine abuse: a literature review for the clinician.

    PubMed

    Brackins, Todd; Brahm, Nancy C; Kissack, Julie C

    2011-12-01

    Methamphetamine (METH) use and dependence is a serious public health concern with implications across multiple areas from societal impact to burden on psychiatric and medical resources. An estimated 8% of admissions to substance abuse treatment programs are related to stimulants with METH/amphetamine abuse. To date, effective pharmacotherapy options to enhance abstinence have not been identified. The objective of this article is to critically review the literature of METH treatment options. Preclinical research and human research with compounds not yet available commercially in the United States will not be included. A literature review was conducted for research on pharmacological treatments for METH use and addiction. Trial information on the use of sertraline, bupropion, mirtazapine, modafinil, dextroamphetamine, ondansetron, risperidone, aripiprazole, baclofen, and gabapentin was reviewed. Aripiprazole trials appeared in the reviewed literature more frequently than the other medications. Based on the findings of this review, no single medication demonstrated consistent efficacy and each trial contained a variety of methodological limitations.

  17. 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.

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

    PubMed Central

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

    2016-01-01

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

  19. Actigraphy-based sleep parameters during the reinstatement of methamphetamine self-administration in rhesus monkeys.

    PubMed

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

    2016-04-01

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

  20. Assessment of lexical semantic judgment abilities in alcohol-dependent subjects: an fMRI study.

    PubMed

    Bagga, D; Singh, N; Modi, S; Kumar, P; Bhattacharya, D; Garg, M L; Khushu, S

    2013-12-01

    Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration.

  1. Head roll dependent variability of subjective visual vertical and ocular counterroll.

    PubMed

    Tarnutzer, Alexander A; Bockisch, Christopher J; Straumann, Dominik

    2009-06-01

    We compared the variability of the subjective visual vertical (SVV) and static ocular counterroll (OCR), and hypothesized a correlation between the measurements because of their shared macular input. SVV and OCR were measured simultaneously in various whole-body roll positions [upright, 45 degrees right-ear down (RED), and 75 degrees RED] in six subjects. Gains of OCR were -0.18 (45 degrees RED) and -0.12 (75 degrees RED), whereas gains of compensation for body roll in the SVV task were -1.11 (45 degrees RED) and -0.96 (75 degrees RED). Normalized SVV and OCR variabilities were not significantly different (P > 0.05), i.e., both increased with increasing roll. Moreover, a significant correlation (R(2) = 0.80, slope = 0.29) between SVV and OCR variabilities was found. Whereas the gain of OCR is different from the gain of SVV, trial-to-trial variability of OCR follows the same roll-dependent modulation observed in SVV variability. We propose that the similarities in variability reflect a common otolith input, which, however, is subject to distinct central processing for determining the gain of SVV and OCR.

  2. Subjective evaluation of running footwear depends on country and assessment method: a bi-national study.

    PubMed

    Kong, Pui W; Lim, Chen Y; Ding, Rui; Sterzing, Thorsten

    2015-01-01

    This study examined (1) the perception of running shoes between China (Beijing) and Singapore and (2) whether running shoe preference depended on assessment methods. One hundred (n = 50 each country) Chinese males subjectively evaluated four shoe models during running by using two assessment procedures. Procedure 1 used a visual analogue scale (VAS) to assess five perception variables. Procedure 2 was a 'head-to-head' comparison of two shoes simultaneously (e.g. left foot: A and right foot: B) to decide which model was preferred. VAS scores were consistently higher in Beijing participants (p < .001), indicating a higher degree of liking. Singapore participants used the lower end but a wider range of the 15 cm scale for shoe discrimination. Moderate agreement was seen between the VAS and 'head-to-head' procedures, with only 14 out of 100 participants matched all 6 pairwise comparisons (median = 4 matches). Footwear companies and researchers should be aware that subjective shoe preference may vary with assessment methods. Practitioner Summary: Footwear preference depends on country and assessment methods. Running shoe perception differed between Beijing and Singapore Chinese, suggesting that footwear recommendation should be country-specific. Individuals' shoe preference measured by visual analogue scale when wearing complete pairs may not reflect that when directly comparing different models in left and right feet.

  3. Melatonin attenuates methamphetamine-induced neuroinflammation through the melatonin receptor in the SH-SY5Y cell line.

    PubMed

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2015-09-01

    Methamphetamine is a well-known psychostimulant drug, the abuse of which is a serious worldwide public health issue. In addition to its addictive effect, methamphetamine exposure has been shown to be associated with neuroinflammation in several brain areas. Several lines of evidence indicate that TNFα plays an important role in the methamphetamine-induced neuroinflammatory processes that result in apoptotic cell death. Many investigators have demonstrated the anti-neuroinflammatory effects of melatonin, but the mechanism by which this occurs still needs to be explored. In this study, we investigated the effect of methamphetamine on TNFα expression and NFκB activation in the neuroblastoma cell line SH-SY5Y. We demonstrated the time-dependent effect of methamphetamine on the induction of TNFα expression as well as IκB degradation and NFκB nuclear translocation. Furthermore, we investigated the effect of melatonin on methamphetamine-induced TNFα overexpression and NFκB activation. The results showed that pretreatment with 100nM melatonin could prevent the TNFα overexpression caused by methamphetamine exposure. This attenuating effect was prevented by pre-incubation with luzindole, an antagonist of the melatonin MT1/MT2 receptors. Furthermore, methamphetamine-induced IκB degradation and NFκB nuclear translocation were also suppressed by pretreatment with melatonin, and pretreatment with luzindole diminished these protective effects. MT2 knockdown by siRNA abrogated the anti-inflammatory effect exerted by melatonin. From these findings, we propose that melatonin exerts its protective effects on methamphetamine-induced neuroinflammation through the membrane receptor, at least in part MT2 subtype, in the SH-SY5Y neuroblastoma cell line.

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

    DTIC Science & Technology

    2014-12-01

    reduced dopamine receptors. We have shown that methamphetamine-mediated neuroprotection is dependent, in part, on the activation of dopamine receptors...This reduction of dopamine receptors also contributes to a condition of chronic inflammation. We have shown that methamphetamine reduces...neuroinlammatory signaling. Thus, the reduction of dopamine receptor mediated signaling could explain the loss of protective effect in aged rats. The MRI time

  5. Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals.

    PubMed

    Grasing, Kenneth; Mathur, Deepan; Newton, Thomas F; DeSouza, Cherilyn

    2010-02-01

    Acetylcholinesterase (AChE) inhibitors increase synaptic levels of acetylcholine (ACh) by inhibiting its breakdown. Donepezil is a reversible AChE inhibitor that is clinically available and relatively selective for inhibiting AChE but not other cholinesterases. Because AChE inhibitors have been shown to decrease the reinforcing effects of cocaine in animals, our hypothesis was that pretreatment with donepezil would attenuate the perceived value and other positive subjective effects of cocaine. We conducted a within-subject, double-blind, placebo-controlled, laboratory-based evaluation of the subjective effects produced by intravenous cocaine in human subjects receiving oral donepezil. Following three days of daily treatment with 5mg of donepezil or oral placebo, participants received intravenous placebo or cocaine (0.18 and 0.36 mg/kg). After a three-day washout period, participants were crossed over to the opposite oral treatment, which was followed by identical intravenous infusions. Donepezil was well-tolerated with only two drug-related adverse events reported that were mild and self-limiting. Treatment with donepezil increased ratings of 'any' and 'good' drug effect produced by low-dose cocaine, without modifying the response to high-dose cocaine. When collapsed across intravenous dose, treatment with donepezil decreased dysphoric effects and somatic symptoms, but did not modify the value of cocaine injections as determined by the Multiple Choice Questionnaire (MCQ). In summary, pretreatment with donepezil potentiated some measures for nonspecific and positive effects of low-dose cocaine. Across all intravenous treatments, participants receiving donepezil reported fewer somatic-dysphoric effects. Neither of these actions support the value of donepezil as a treatment for cocaine dependence.

  6. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

    PubMed

    Volkow, N D; Chang, L; Wang, G J; Fowler, J S; Franceschi, D; Sedler, M; Gatley, S J; Miller, E; Hitzemann, R; Ding, Y S; Logan, J

    2001-12-01

    Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

  7. Effects of methamphetamine on response rate: a microstructural analysis.

    PubMed

    Bennett, J Adam; Hughes, Christine E; Pitts, Raymond C

    2007-06-01

    Key pecking in pigeons was maintained under a multiple random-interval (RI) 1-min, RI 4-min schedule of food presentation. Several doses (0.3-5.6 mg/kg) of methamphetamine were administered, and effects on overall response rates and on the microstructure of responding were characterized. In three of the four pigeons, methamphetamine dose-dependently decreased overall response rate in both components; in the fourth pigeon, intermediate doses increased response rates. Log-survivor analyses did not produce the clear "broken-stick" pattern previously reported with rats [Shull, R.L., Gaynor, S.T., Grimes, J.A., 2001. Response rate viewed as engagement bouts: effects of relative reinforcement and schedule type. J. Exp. Anal. Behav. 75, 247-274]. A fine-grained analysis of inter-response times (IRTs) revealed clear bands of responding around certain IRT durations. Methamphetamine tended to decrease the frequency of IRTs in the shorter bands and increase the frequency of IRTs across all bins greater than 2s. These results suggest that (a) survivor analyses may not extend to pigeon key pecking, (b) microstructural analyses can reveal order not evident with overall response rate, and (c) a detailed analysis of responding might prove more useful than summary measures in characterizing drug effects on behavior.

  8. Methamphetamine residue dermal transfer efficiencies from household surfaces.

    PubMed

    Van Dyke, Mike; Martyny, John W; Serrano, Kate A

    2014-01-01

    Methamphetamine contamination from illegal production operations poses a potential health concern for emergency responders, child protective services, law enforcement, and children living in contaminated structures. The objective of this study was to evaluate dermal transfer efficiencies of methamphetamine from contaminated household surfaces. These transfer efficiencies are lacking for methamphetamine, and would be beneficial for use in exposure models. Surfaces were contaminated using a simulated smoking method in a stainless steel chamber. Household surfaces were carpet, painted drywall, and linoleum. Dermal transfer efficiencies were obtained using cotton gloves for two hand conditions, dry or saliva moistened (wet). In addition, three contact scenarios were evaluated for both hand conditions: one, two, or three contacts with contaminated surfaces. Dermal transfer efficiencies were calculated for both hand conditions and used as inputs in a Stochastic Human Exposure and Dose Simulation model (SHEDS-Multimedia, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, N.C.). Results of this study showed that average dermal transfer efficiencies of methamphetamine ranged from 11% for dry hands to 26% for wet hands. There was a significantly higher wet transfer as compared to dry transfer for all surfaces. For wet hands, dermal transfer depended on surface type with higher transfer from carpet and linoleum as compared to drywall. Based on our estimates of dermal transfer efficiency, a surface contamination clearance level of 1.5 μg/100 cm(2) may not ensure absorbed doses remain below the level associated with adverse health effects in all cases. Additional dermal transfer studies should be performed using skin surrogates that may better predict actual skin transfer.

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

    PubMed

    Kuribara, H; Tadokoro, S

    1985-09-01

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

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

    PubMed Central

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

    2015-01-01

    Rationale Monoamine releasers with prominent dopaminergic actions, e.g., d-methamphetamine (d-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, d-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. Objectives The l-isomer of methamphetamine (l-MA), unlike d-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether l-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Methods Separate groups (N=4-5) of rhesus monkeys were studied to determine whether l-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and, (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. Results l-MA, like d-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10 day treatments with continuously infused l-MA (0.032-0.32 mg/kg/hr, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. Conclusions These results indicate that l-MA both shares discriminative-stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. l-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder. PMID:26713332

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Processing subject-verb agreement in a second language depends on proficiency

    PubMed Central

    Hoshino, Noriko; Dussias, Paola E.; Kroll, Judith F.

    2010-01-01

    Subject-verb agreement is a computation that is often difficult to execute perfectly in the first language (L1) and even more difficult to produce skillfully in a second language (L2). In this study, we examined the way in which bilingual speakers complete sentence fragments in a manner that reflects access to both grammatical and conceptual number. In two experiments, we show that bilingual speakers are sensitive to both grammatical and conceptual number in the L1 and grammatical number agreement in the L2. However, only highly proficient bilinguals are also sensitive to conceptual number in the L2. The results suggest that the extent to which speakers are able to exploit conceptual information during speech planning depends on the level of language proficiency. PMID:20640178

  16. Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations

    PubMed Central

    Luo, Xingguang; Zuo, Lingjun; Kranzler, Henry; Zhang, Huiping; Wang, Shuang; Gelernter, Joel

    2011-01-01

    Background Personality traits are among the most complex quantitative traits. Certain personality traits are associated with substance dependence (SD); genetic factors may influence both. Associations between opioid receptor (OPR) genes and SD have been reported. This study investigated the relationship between OPR genes and personality traits in a case-control sample. Methods We assessed dimensions of the five-factor model of personality in 556 subjects: 250 with SD [181 European-Americans (EAs) and 69 African-Americans (AAs)] and 306 healthy subjects (266 EAs and 40 AAs). We genotyped 20 OPRM1 markers, 8 OPRD1 markers, and 7 OPRK1 markers, and 38 unlinked ancestry-informative markers in these subjects. The relationships between OPR genes and personality traits were examined using MANCOVA, controlling for gene-gene interaction effects and potential confounders. Associations were decomposed by Roy-Bargmann Stepdown ANCOVA. Results Personality traits were associated as main or interaction effects with the haplotypes, diplotypes, alleles and genotypes at the three OPR genes (0.002

  17. Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations.

    PubMed

    Luo, Xingguang; Zuo, Lingjun; Kranzler, Henry; Zhang, Huiping; Wang, Shuang; Gelernter, Joel

    2008-10-05

    Personality traits are among the most complex quantitative traits. Certain personality traits are associated with substance dependence (SD); genetic factors may influence both. Associations between opioid receptor (OPR) genes and SD have been reported. This study investigated the relationship between OPR genes and personality traits in a case-control sample. We assessed dimensions of the five-factor model of personality in 556 subjects: 250 with SD [181 European-Americans (EAs) and 69 African-Americans (AAs)] and 306 healthy subjects (266 EAs and 40 AAs). We genotyped 20 OPRM1 markers, 8 OPRD1 markers, and 7 OPRK1 markers, and 38 unlinked ancestry-informative markers in these subjects. The relationships between OPR genes and personality traits were examined using MANCOVA, controlling for gene-gene interaction effects and potential confounders. Associations were decomposed by Roy-Bargmann Stepdown ANCOVA. We found that personality traits were associated as main or interaction effects with the haplotypes, diplotypes, alleles and genotypes at the three OPR genes (0.002 < P < 0.046 from MANCOVA; 0.0004 < P < 0.049 from ANCOVA). Diplotype TTAGGA/TTCAGA at OPRM1 had main effects on Extraversion (P = 0.008), and diplotypes OPRM1(insertion mark)TTCAGA/TTCAGA and OPRD1(insertion mark)CAC/TAC had interaction effects on Openness (P = 0.010) after conservative correction for multiple testing. The present study demonstrates that the genes encoding the mu-, delta-, and kappa-opioid receptors may contribute to variation in personality traits. Further, the three OPR genes have significant interaction effects on personality traits. This work provides additional evidence that personality traits and SD have a partially overlapping genetic basis.

  18. 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

  19. Methamphetamine craving induced in an online virtual reality environment.

    PubMed

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

    2010-10-01

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

  20. Quantization and instability of the damped harmonic oscillator subject to a time-dependent force

    SciTech Connect

    Majima, H. Suzuki, A.

    2011-12-15

    We consider the one-dimensional motion of a particle immersed in a potential field U(x) under the influence of a frictional (dissipative) force linear in velocity (-{gamma}x) and a time-dependent external force (K(t)). The dissipative system subject to these forces is discussed by introducing the extended Bateman's system, which is described by the Lagrangian: L=mxy-U(x+1/2 y)+U(x-1/2 y)+({gamma})/2 (xy-yx)-xK(t)+yK(t), which leads to the familiar classical equations of motion for the dissipative (open) system. The equation for a variable y is the time-reversed of the x motion. We discuss the extended Bateman dual Lagrangian and Hamiltonian by setting U(x{+-}y/2)=1/2 k(x{+-}y/2){sup 2} specifically for a dual extended damped-amplified harmonic oscillator subject to the time-dependent external force. We show the method of quantizing such dissipative systems, namely the canonical quantization of the extended Bateman's Hamiltonian H. The Heisenberg equations of motion utilizing the quantized Hamiltonian H surely lead to the equations of motion for the dissipative dynamical quantum systems, which are the quantum analog of the corresponding classical systems. To discuss the stability of the quantum dissipative system due to the influence of an external force K(t) and the dissipative force, we derived a formula for transition amplitudes of the dissipative system with the help of the perturbation analysis. The formula is specifically applied for a damped-amplified harmonic oscillator subject to the impulsive force. This formula is used to study the influence of dissipation such as the instability due to the dissipative force and/or the applied impulsive force. - Highlights: > A method of quantizing dissipative systems is presented. > In order to obtain the method, we apply Bateman's dual system approach. > A formula for a transition amplitude is derived. > We use the formula to study the instability of the dissipative systems.

  1. Individual differences are critical in determining modafinil-induced behavioral sensitization and cross-sensitization with methamphetamine in mice.

    PubMed

    Soeiro, Aline da Costa; Moreira, Karin Di Monteiro; Abrahao, Karina Possa; Quadros, Isabel Marian Hartmann; Oliveira, Maria Gabriela Menezes

    2012-08-01

    Modafinil is a non-amphetaminic psychostimulant used therapeutically for sleep and psychiatric disorders. However, some studies indicate that modafinil can have addictive properties. The present study examined whether modafinil can produce behavioral sensitization in mice, an experience and drug-dependent behavioral adaptation, and if individual differences play a role in this process. We further tested context-related factors and cross-sensitization between modafinil and methamphetamine. Important individual differences in the behavioral sensitization of Swiss Albino mice were observed after repeated administration of 50 mg/kg modafinil (Experiment 1), or 1 mg/kg methamphetamine (Experiment 2). Only mice classified as sensitized subgroup developed clear behavioral sensitization to the drugs. After a withdrawal period, mice received challenges of modafinil (Experiment 1), or methamphetamine (Experiment 2) and locomotor activity was evaluated in the activity cages (previous context) and in the open field arena (new context) in order to evaluate the context dependency of behavioral sensitization. The expression of sensitization to modafinil, but not to methamphetamine, was affected by contextual testing conditions, since modafinil-sensitized mice only expressed sensitization in the activity cage, but not in the open field. Subsequently, locomotor cross-sensitization between methamphetamine and modafinil was assessed by challenging modafinil-pretreated mice with 1mg/kg methamphetamine (Experiment 1), and methamphetamine-pretreated mice with 50mg/kg modafinil (Experiment 2). We observed a symmetrical cross-sensitization between the drugs only in those mice that were classified as sensitized subgroup. Our findings indicate that repeated exposure to modafinil induces behavioral sensitization only in some animals by similar neurobiological, but not contextual, mechanisms to those of methamphetamine.

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

    PubMed

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

    2009-01-01

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

  3. Raman spectroscopy as a simple, rapid, nondestructive screening test for methamphetamine in clandestine laboratory liquids.

    PubMed

    Triplett, Jeremy S; Hatfield, Jennifer A; Kaeff, Tracy L; Ramsey, Christopher R; Robinson, Susan D; Standifer, Allison F

    2013-11-01

    Raman spectroscopy has found increased use in the forensic controlled substances laboratory in recent years due to its rapid and nondestructive analysis capabilities. Here, Raman spectroscopy as a screening test for methamphetamine in clandestine laboratory liquid samples is discussed as a way to improve the efficiency of a laboratory by identifying the most probative samples for further workup among multiple samples submitted for analysis. Solutions of methamphetamine in ethanol, diethyl ether, and Coleman fuel were prepared in concentrations ranging from 0.5% to 10% w/v, and Raman spectra of each were collected. A concentration-dependent Raman peak was observed at 1003 per cm in each solution in 4% w/v and greater solutions. Case samples were analyzed and also found to reliably contain this diagnostic peak when methamphetamine was present. The use of this diagnostic indicator can save the forensic controlled substances laboratory time and materials when analyzing clandestine laboratory liquid submissions.

  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. A novel dopamine D3 receptor antagonist YQA14 inhibits methamphetamine self-administration and relapse to drug-seeking behaviour in rats.

    PubMed

    Chen, Ying; Song, Rui; Yang, Ri-Fang; Wu, Ning; Li, Jin

    2014-11-15

    Growing preclinical evidence suggests that dopamine D3 receptor antagonists are promising for the treatment of addiction. We have previously reported a novel dopamine D3 receptor antagonist YQA14 with better pharmacokinetic behaviours and pharmacotherapeutic efficacy than other tested compounds in attenuating the reward and relapse of cocaine. In the present study, we investigated whether YQA14 can similarly inhibit methamphetamine self-administration and cue- or methamphetamine-trigged reinstatement of drug-seeking behaviour. The research illustrated that systemic administration of YQA14 (6.25-25mg/kg, i.p. 20min prior to methamphetamine) failed to alter methamphetamine (0.05mg/kg) self-administration under fixed-ratio 2. However, YQA14 (6.25-25mg/kg, i.p. 20min prior to methamphetamine) significantly and dose-dependently reduced methamphetamine self-administration under fixed-ratio 2 by a low dose (0.006, 0.0125, 0.025mg/kg) of methamphetamine and shifted the dose curve right and down. Further, YQA14 also lowered the break point under progressive-ratio reinforcement conditions in rats. Finally, YQA14 also significantly inhibited cue- or methamphetamine-triggered reinstatement of extinguished drug-seeking behaviour. Overall, our findings suggest that blockade of the dopamine D3 receptor by YQA14 attenuated the rewarding and incentive motivational effects of methamphetamine in rats and may have pharmacotherapeutic potential in the treatment of methamphetamine addiction. Thus, YQA14 deserves further investigation as a promising medication for the treatment of addiction.

  6. Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat.

    PubMed

    Cadet, Jean Lud; Brannock, Christie; Jayanthi, Subramaniam; Krasnova, Irina N

    2015-04-01

    Methamphetamine use disorder is a chronic neuropsychiatric disorder characterized by recurrent binge episodes, intervals of abstinence, and relapses to drug use. Humans addicted to methamphetamine experience various degrees of cognitive deficits and other neurological abnormalities that complicate their activities of daily living and their participation in treatment programs. Importantly, models of methamphetamine addiction in rodents have shown that animals will readily learn to give themselves methamphetamine. Rats also accelerate their intake over time. Microarray studies have also shown that methamphetamine taking is associated with major transcriptional changes in the striatum measured within a short or longer time after cessation of drug taking. After a 2-h withdrawal time, there was increased expression of genes that participate in transcription regulation. These included cyclic AMP response element binding (CREB), ETS domain-containing protein (ELK1), and members of the FOS family of transcription factors. Other genes of interest include brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor, type 2 (TrkB), and synaptophysin. Methamphetamine-induced transcription was found to be regulated via phosphorylated CREB-dependent events. After a 30-day withdrawal from methamphetamine self-administration, however, there was mostly decreased expression of transcription factors including junD. There was also downregulation of genes whose protein products are constituents of chromatin-remodeling complexes. Altogether, these genome-wide results show that methamphetamine abuse might be associated with altered regulation of a diversity of gene networks that impact cellular and synaptic functions. These transcriptional changes might serve as triggers for the neuropsychiatric presentations of humans who abuse this drug. Better understanding of the way that gene products interact to cause methamphetamine addiction will help to develop better pharmacological

  7. 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

  8. Methamphetamine treatment outcomes among gay men attending a LGBTI-specific treatment service in Sydney, Australia

    PubMed Central

    Kolstee, Johann; Lambert, Sarah; Ness, Ross; Hannan, Siobhan; Holt, Martin

    2017-01-01

    Gay and bisexual men (GBM) report higher rates of methamphetamine use compared to heterosexual men, and thus have a heightened risk of developing problems from their use. We examined treatment outcomes among GBM clients receiving outpatient counseling at a lesbian, gay, bisexual, transgender and intersex (LGBTI)-specific, harm reduction treatment service in Sydney, Australia. GBM receiving treatment for methamphetamine use from ACON’s Substance Support Service between 2012–15 (n = 101) were interviewed at treatment commencement, and after 4 sessions (n = 60; follow-up 1) and 8 sessions (n = 32; follow-up 2). At each interview, clients completed measures of methamphetamine use and dependence, other substance use, injecting risk practices, psychological distress and quality of life. The median age of participants was 41 years and 56.4% identified as HIV-positive. Participants attended a median of 5 sessions and attended treatment for a median of 112 days. There was a significant reduction in the median days of methamphetamine use in the previous 4 weeks between baseline (4 days), follow-up 1 (2 days) and follow-up 2 (2 days; p = .001). There was a significant reduction in the proportion of participants reporting methamphetamine dependence between baseline (92.1%), follow-up 1 (78.3%) and follow-up 2 (71.9%, p < .001). There were also significant reductions in psychological distress (p < .001), and significant improvements in quality of life (p < .001). Clients showed reductions in methamphetamine use and improved psychosocial functioning over time, demonstrating the potential effectiveness of a LGBTI-specific treatment service. PMID:28207902

  9. Methamphetamine treatment outcomes among gay men attending a LGBTI-specific treatment service in Sydney, Australia.

    PubMed

    Lea, Toby; Kolstee, Johann; Lambert, Sarah; Ness, Ross; Hannan, Siobhan; Holt, Martin

    2017-01-01

    Gay and bisexual men (GBM) report higher rates of methamphetamine use compared to heterosexual men, and thus have a heightened risk of developing problems from their use. We examined treatment outcomes among GBM clients receiving outpatient counseling at a lesbian, gay, bisexual, transgender and intersex (LGBTI)-specific, harm reduction treatment service in Sydney, Australia. GBM receiving treatment for methamphetamine use from ACON's Substance Support Service between 2012-15 (n = 101) were interviewed at treatment commencement, and after 4 sessions (n = 60; follow-up 1) and 8 sessions (n = 32; follow-up 2). At each interview, clients completed measures of methamphetamine use and dependence, other substance use, injecting risk practices, psychological distress and quality of life. The median age of participants was 41 years and 56.4% identified as HIV-positive. Participants attended a median of 5 sessions and attended treatment for a median of 112 days. There was a significant reduction in the median days of methamphetamine use in the previous 4 weeks between baseline (4 days), follow-up 1 (2 days) and follow-up 2 (2 days; p = .001). There was a significant reduction in the proportion of participants reporting methamphetamine dependence between baseline (92.1%), follow-up 1 (78.3%) and follow-up 2 (71.9%, p < .001). There were also significant reductions in psychological distress (p < .001), and significant improvements in quality of life (p < .001). Clients showed reductions in methamphetamine use and improved psychosocial functioning over time, demonstrating the potential effectiveness of a LGBTI-specific treatment service.

  10. Liposomal melatonin rescues methamphetamine-elicited mitochondrial burdens, pro-apoptosis, and dopaminergic degeneration through the inhibition PKCδ gene.

    PubMed

    Nguyen, Xuan-Khanh Thi; Lee, Jaehwi; Shin, Eun-Joo; Dang, Duy-Khanh; Jeong, Ji Hoon; Nguyen, Thuy-Ty Lan; Nam, Yunsung; Cho, Hyun-Jong; Lee, Jae-Chul; Park, Dae Hun; Jang, Choon-Gon; Hong, Jau-Shyong; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2015-01-01

    We have demonstrated that mitochondrial oxidative damage and PKCδ overexpression contribute to methamphetamine-induced dopaminergic degeneration. Although it is recognized that antioxidant melatonin is effective in preventing neurotoxicity induced by methamphetamine, its precise mechanism remains elusive. C57BL/6J wild-type mice exhibited a similar degree of dopaminergic deficit when methamphetamine was administered during light and dark phases. Furthermore, dopaminergic neuroprotection by genetic inhibition of PKCδ during the light phase was comparable to that during the dark phase. Thus, we have focused on the light phase to examine whether melatonin modulates PKCδ-mediated neurotoxic signaling after multiple high doses of methamphetamine. To enhance the bioavailability of melatonin, we applied liposomal melatonin. Treatment with methamphetamine resulted in hyperthermia, mitochondrial translocation of PKCδ, oxidative damage (mitochondria > cytosol), mitochondrial dysfunction, pro-apoptotic changes, ultrastructural mitochondrial degeneration, dopaminergic degeneration, and behavioral impairment in wild-type mice. Treatment with liposomal melatonin resulted in a dose-dependent attenuation against degenerative changes induced by methamphetamine in wild-type mice. Attenuation by liposomal melatonin might be comparable to that by genetic inhibition (using PKCδ((-/-)) mice or PKCδ antisense oligonucleotide). However, liposomal melatonin did not show any additional protective effects on the attenuation by genetic inhibition of PKCδ. Our results suggest that the circadian cycle cannot be a key factor in modulating methamphetamine toxicity under the current experimental condition and that PKCδ is one of the critical target genes for melatonin-mediated protective effects against mitochondrial burdens (dysfunction), oxidative stress, pro-apoptosis, and dopaminergic degeneration induced by methamphetamine.

  11. Growing Old With Ice: A Review of the Potential Consequences of Methamphetamine Abuse in Australian Older Adults.

    PubMed

    Searby, Adam; Maude, Phil; McGrath, Ian

    2015-01-01

    This review analyzes contemporary literature in the context of Australian aging methamphetamine users, service response, and challenges to provision of care to this population. The article focuses on Australian literature with comparisons made with trends arising from international scholarship. Searches of the CINAHL, ProQuest, and Scopus electronic journal databases were performed in early 2014 as part of a wider study investigating dual diagnosis in older adults. Methamphetamine abuse is common in individuals with comorbid mental illness. The literature presented in this review outlines potential neuropsychological and persistent psychiatric sequelae associated with the use of methamphetamine, along with a number of concerning behaviors prevalent in individuals with comorbid human immunodeficiency virus-positive status. Despite an abundance of literature discussing methamphetamine use in adult populations, this is the first review exploring methamphetamine use in the context of aging and older adult mental health. Contemporary literature suggests that methamphetamine dependence will be a significant challenge for services that cater to older adults, requiring further research to fully assess the impact this cohort will have on the healthcare system.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2017-01-01

    Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. PMID:26334786

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

    PubMed

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

    2015-12-01

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

  15. Glycaemic responses after ingestion of some local foods by non-insulin dependent diabetic subjects.

    PubMed

    Ayuo, P O; Ettyang, G A

    1996-12-01

    Fifteen non-insulin dependent diabetic volunteers, aged 51 +/- 3.9 years, were studied over a two month period to determine their glycaemic responses to various local foods. They were all on chlorpropamide and one subject was removed from analysis due to concurrent use of insulin. They received on separate occasions two servings of white bread, one serving of: brown bread, white lice, English potatoes, maize meal, millet and cassava each. Each meal contained 50 g of carbohydrate. A total of 107 glucose tolerance tests (GTTs) were performed and the glycaemic index (GI) for each food calculated. The mean blood sugars at 0,60 and 120 minutes were comparable for each food, and the peak rise occurred at 60 minutes. The highest rise (4.0 mmol/I) was seen with millet porridge. The highest GI was seen with white rice and the lowest with English potatoes (159.9 and 34.3 respectively). Overall, the cereals conferred higher GIs than the root vegetables. The GIs of English potatoes, maize meal, millet and cassava significantly differed from that of white bread. It is concluded that, using GIs, dietary guidelines comprising locally available and affordable foods can be made.

  16. A new rate-dependent unidirectional composite model - Application to panels subjected to underwater blast

    NASA Astrophysics Data System (ADS)

    Wei, Xiaoding; de Vaucorbeil, Alban; Tran, Phuong; Espinosa, Horacio D.

    2013-06-01

    In this study, we developed a finite element fluid-structure interaction model to understand the deformation and failure mechanisms of both monolithic and sandwich composite panels. A new failure criterion that includes strain-rate effects was formulated and implemented to simulate different damage modes in unidirectional glass fiber/matrix composites. The laminate model uses Hashin's fiber failure criterion and a modified Tsai-Wu matrix failure criterion. The composite moduli are degraded using five damage variables, which are updated in the post-failure regime by means of a linear softening law governed by an energy release criterion. A key feature in the formulation is the distinction between fiber rupture and pull-out by introducing a modified fracture toughness, which varies from a fiber tensile toughness to a matrix tensile toughness as a function of the ratio of longitudinal normal stress to effective shear stress. The delamination between laminas is modeled by a strain-rate sensitive cohesive law. In the case of sandwich panels, core compaction is modeled by a crushable foam plasticity model with volumetric hardening and strain-rate sensitivity. These constitutive descriptions were used to predict deformation histories, fiber/matrix damage patterns, and inter-lamina delamination, for both monolithic and sandwich composite panels subjected to underwater blast. The numerical predictions were compared with experimental observations. We demonstrate that the new rate dependent composite damage model captures the spatial distribution and magnitude of damage significantly more accurately than previously developed models.

  17. What You Need to Know about Drugs: Methamphetamines

    MedlinePlus

    ... mouth, hot flashes, and dizziness. People who abuse methamphetamines feel high and full of energy. They think the drug will allow their bodies to keep going and going. But methamphetamines are very damaging to the body and brain, ...

  18. 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 ...

  19. 13C-nuclear magnetic resonance spectroscopy studies of hepatic glucose metabolism in normal subjects and subjects with insulin-dependent diabetes mellitus.

    PubMed Central

    Cline, G W; Rothman, D L; Magnusson, I; Katz, L D; Shulman, G I

    1994-01-01

    To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux through hepatic pyruvate dehydrogenase, we used 13C-nuclear magnetic resonance spectroscopy to monitor the peak intensity of the C1 resonance of the glucosyl units of hepatic glycogen, in combination with acetaminophen to sample the hepatic UDP-glucose pool and phenylacetate to sample the hepatic glutamine pool, during a hyperglycemic-hyperinsulinemic clamp using [1-13C]-glucose. Five subjects with poorly controlled IDDM and six age-weight-matched control subjects were clamped at a mean plasma glucose concentration of approximately 9 mM and mean plasma insulin concentrations approximately 400 pM for 5 h. Rates of hepatic glycogen synthesis were similar in both groups (approximately 0.43 +/- 0.09 mumol/ml liver min). However, flux through the indirect pathway of glycogen synthesis (3 carbon units-->-->glycogen) was increased by approximately 50% (P < 0.05), whereas the relative contribution of pyruvate oxidation to TCA cycle flux was decreased by approximately 30% (P < 0.05) in the IDDM subjects compared to the control subjects. These studies demonstrate that patients with poorly controlled insulin-dependent diabetes mellitus have augmented hepatic gluconeogenesis and relative decreased rates of hepatic pyruvate oxidation. These abnormalities are not immediately reversed by normalizing intraportal concentrations of glucose, insulin, and glucagon and may contribute to postprandial hyperglycemia. PMID:7989593

  20. 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.

  1. 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.

  2. 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.

  3. Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle

    PubMed Central

    Hossain, Kazi Jahangir; Kamal, Md Mustafa; Ahsan, Monira; Islam, SK Nazrul

    2007-01-01

    Background Use of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18–45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry. Results Results showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels. Conclusion Illicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations. PMID

  4. 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.

  5. 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…

  6. Violence perpetrated by women who use methamphetamine

    PubMed Central

    HAMILTON, ALISON B.; GOEDERS, NICHOLAS E.

    2015-01-01

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

  7. Local hippocampal methamphetamine-induced reinforcement.

    PubMed

    Ricoy, Ulises M; Martinez, Joe L

    2009-01-01

    Drug abuse and addiction are major problems in the United States. In particular methamphetamine (METH) use has increased dramatically. A greater understanding of how METH acts on the brain to induce addiction may lead to better therapeutic targets for this problem. The hippocampus is recognized as an important structure in learning and memory, but is not typically associated with drug reinforcement or reward processes. Here, the focus is on the hippocampus which has been largely ignored in the addiction literature as compared to the nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC). The results show that METH administered unilaterally via a microdialysis probe to rats' right dorsal hippocampus will induce drug-seeking (place preference) and drug-taking (lever-pressing) behavior. Furthermore, both of these responses are dependent on local dopamine (DA) receptor activation, as they are impaired by a selective D(1)/D(5) receptor antagonist. The results suggest that the hippocampus is part of the brain's reward circuit that underlies addiction.

  8. Gravity dependence of the effect of optokinetic stimulation on the subject visual vertical.

    PubMed

    Ward, Bryan K; Bockisch, Christopher J; Caramia, Nicoletta; Bertolini, Giovanni; Tarnutzer, Alexander Andrea

    2017-02-01

    Accurate and precise estimates of direction of gravity are essential for spatial orientation. According to Bayesian theory, multisensory vestibular, visual and proprioceptive input is centrally integrated in a weighted fashion based on the reliability of the component sensory signals. For otolithic input, a decreasing signal-to-noise ratio was demonstrated with increasing roll-angle. We hypothesized that the weights of vestibular (otolithic) and extra-vestibular (visual/proprioceptive) sensors are roll-angle dependent and predicted an increased weight of extra-vestibular cues with increasing roll-angle, potentially following the Bayesian hypothesis. To probe this concept, the subjective visual vertical (SVV) was assessed in different roll-positions (≤±120°, steps=30°, n=10) with/without presenting an optokinetic stimulus (velocity=±60°/s). The optokinetic stimulus biased the SVV towards the direction of stimulus-rotation for roll-angles ≥±30° (p<0.005). Offsets grew from 3.9±1.8° (upright) to 22.1±11.8° (±120° roll-tilt, p<0.001). Trial-to-trial variability increased with roll-angle, demonstrating a non-significant increase when providing optokinetic stimulation. Variability and optokinetic bias were correlated (R(2)=0.71, slope=0.71, 95%-confidence-interval=0.57-0.86). An optimal-observer model combining an optokinetic bias with vestibular input reproduced measured errors closely. These findings support the hypothesis of a weighted multisensory-integration when estimating direction of gravity with optokinetic stimulation. Visual input was weighted more when vestibular input became less reliable, i.e., at larger roll-tilt angles. However, according to Bayesian theory, the variability of combined cues is always lower than the variability of each source cue. If the observed increase in variability -although non-significant- is true, either it must depend on an additional source of variability, added after SVV-computation, or it would conflict with

  9. A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

    PubMed Central

    Batra, Vinita; Guerin, Glenn F.; Goeders, Nicholas E.; Wilden, Jessica A.

    2016-01-01

    Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID:26863392

  10. A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration.

    PubMed

    Batra, Vinita; Guerin, Glenn F; Goeders, Nicholas E; Wilden, Jessica A

    2016-01-22

    Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

  11. 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.

  12. 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 ...

  13. Methamphetamine

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  14. 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

  15. Use of MDA (the "love drug") and methamphetamine in Toronto by unsuspecting users of ecstasy (MDMA).

    PubMed

    Kalasinsky, Kathryn S; Hugel, John; Kish, Stephen J

    2004-09-01

    It has recently been reported that purity of illicit tablets of ecstasy (MDMA) is now high. Our objective was to confirm whether hair of drug users, who request only ecstasy from their supplier, contains MDMA in the absence of other drugs. GC-MS analysis of scalp hair segments disclosed the presence of MDMA in 19 of 21 subjects and amphetamine/methamphetamine in eight subjects. Surprisingly, seven subjects had hair levels of the MDMA metabolite, MDA, equal to or greater than those of MDMA, suggesting use of MDA in addition to that of MDMA. These amphetamine derivatives might be included by clandestine laboratories to enhance effects of the drug cocktail or because of a perception that MDA synthesis might be simpler than that of MDMA. Drug users and investigators examining possible brain neurotoxic effects of MDMA need to consider that "ecstasy" tablets can contain MDA and methamphetamine despite no demand for the drugs.

  16. Clinical Characteristics of Subjects with Sulfonylurea-Dependent Type 2 Diabetes

    PubMed Central

    Min, Se Hee; Kwak, Soo Heon; Cho, Young Min; Park, Kyong Soo

    2015-01-01

    Background Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients. Methods We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride ≤2 mg/day or equivalent dose); after discontinuation of SU, HbA1c increased ≥1.2% within 3 months or ≥1.5% within 6 months; and after resuming SU, HbA1c reduction was ≥0.8% or reduction of fasting plasma glucose was ≥40 mg/dL within 3 months. Patients with impaired hepatic or renal function, and steroid users were excluded. Results Nineteen subjects were enrolled: after averaged 4.8±1.5 months of SU-free period, HbA1c increased from 6.7%±0.4% to 8.8%±0.8% even though adding other OAD such as gliptins. However, HbA1c decreased to 7.4%±0.7% after resuming SU within 2.4±0.8 months. There was no sexual predominance. Despite their old age (67±11 years) and long duration of diabetes (18±10 years), fasting C-peptide was relatively well-reserved (3.9±2.6 ng/mL), and nephropathy was not observed (albumin-creatinine ratio 21.2±16.6 mg/g and estimated glomerular filtration rate 75.8±18.0 mL/min/1.73 m2). Strong family history was also noted (73.7%). Conclusion Despite hypoglycemia risk of SU, it seemed indispensable for a subset of patients with regard to insulin secretion. Genetic influences would be evaluated. PMID:26354492

  17. Spend today, clean tomorrow: Predicting methamphetamine abstinence in a randomized controlled trial

    PubMed Central

    Murtaugh, Kimberly Ling; Krishnamurti, Tamar; Davis, Alexander L.; Reback, Cathy J.; Shoptaw, Steven

    2013-01-01

    Objective This secondary analysis of data from a randomized controlled trial tested two behavioral economics mechanisms (substitutability and delay discounting) to explain outcomes using contingency management (CM) for methamphetamine dependence. Frequency and purchase type (hedonic/utilitarian and consumable/durable) of CM payments were also examined. Methods 82 methamphetamine-dependent gay/bisexual men randomly assigned to conditions delivering CM received monetary vouchers in exchange for stimulant-negative urine samples in a 16-week trial requiring thrice weekly visits (Shoptaw et al., 2005). At any visit participants could redeem vouchers for goods. A time-lagged counting process Cox Proportional Hazards model for recurrent event survival analysis examined aspects of the frequency and type of these CM purchases. Results After controlling for severity of baseline methamphetamine use and accumulated CM wealth, as measured by cumulative successful earning days, participants who redeemed CM earnings at any visit (“spenders”) were significantly more likely to produce stimulant-negative urine samples in the subsequent visit, compared to those who did not redeem (“savers”) 1.011* [1.005, 1.017], Z=3.43, p<0.001. Conclusions Findings support the economic concept of substitutability of CM purchases and explain trial outcomes as a function of frequency of CM purchases rather than frequency or accumulated total CM earnings. Promotion of frequent purchases in incentive-based programs should facilitate substitution for the perceived value of methamphetamine and improve abstinence outcomes. PMID:24001246

  18. 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.

  19. Amphetamines in washed hair of demonstrated users and workplace subjects.

    PubMed

    Cairns, Thomas; Hill, Virginia; Schaffer, Michael; Thistle, William

    2004-10-29

    In a study of volunteer subjects from drug rehabilitation programs, methamphetamine and amphetamine levels were determined in the hair of 40 subjects who had produced MS-confirmed methamphetamine-positive urine results. The samples were tested by radioimmunoassay and analyzed by LC/MS/MS after being washed with the 3.75-h wash procedure developed by this laboratory. In addition, results of non-user and workplace samples are presented. In workplace samples, levels of methamphetamine, amphetamine, methylenedioxy-methamphetamine (MDMA), and methylenedioxyamphetamine (MDA), are reported. The range of methamphetamine levels in the clinical samples (170-34,400 pg/mg hair) was not different from the workplace population (from less than the cutoff of 500 pg/mg to >20,000 pg/mg hair), but the workplace population had a lower percentage of high levels of drug. Amphetamine levels were found to vary widely in both populations, at all levels of methamphetamine. In the clinical population, no samples were positive for MDMA; in MDMA-positive workplace samples, the levels ranged from below the cutoff of 500 to >20,000 pg/mg, with MDA levels varying widely, similar to amphetamine levels in methamphetamine-positive samples.

  20. Executive functions among individuals with methamphetamine or alcohol as drugs of choice: preliminary observations.

    PubMed

    Gonzalez, Raul; Bechara, Antoine; Martin, Eileen M

    2007-02-01

    Substance dependent individuals (SDIs) are frequently, but not invariably, impaired on tasks of executive functions. In this study, we examine patterns of executive performance among subjects with different self-reported "drug of choice" (defined as substance used>80% of the time prior to abstinence). Subjects were 33 abstinent SDIs receiving inpatient treatment and 19 non-SDI normal controls (NC) well-matched on age, sex, ethnicity, and VIQ, who were assessed using the Iowa Gambling Task (GT) and a delayed non-match to sample task (DNM): measures of decision making and working memory, respectively. Seventeen SDIs identified alcohol (AL group) and 16 SDIs identified methamphetamine (METH group) as their drug of choice. Overall, the METH group performed more poorly than the NC and AL groups on both tasks, with the largest differences observed in working memory. The AL group was not significantly impaired overall compared to NCs on either task, but showed subtle abnormalities of GT performance similar to the METH group. These preliminary findings suggest that self-reported drug of choice on admission to treatment may be associated with different patterns of executive performance during early recovery.

  1. 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.

  2. Effects of Length of Abstinence on Decision-Making and Craving in Methamphetamine Abusers

    PubMed Central

    Wang, Guibin; Shi, Jie; Chen, Na; Xu, Lingzhi; Li, Jiali; Li, Peng; Sun, Yan; Lu, Lin

    2013-01-01

    Rationale The majority of drug abusers are incapable of sustaining abstinence over any length of time. Accumulating evidence has linked intense and involuntary craving, Impulsive decision-making and mood disturbances to risk for relapse. However, little is known about temporal changes of these neuropsychological functions in methamphetamine (METH)-dependent individuals. Objectives To investigate the effect of length of abstinence on decision-making, craving (baseline and cue-induced), and emotional state in METH-addicted individuals. Methods In this cross-sectional study, 183 adult METH-dependent patients at an addiction rehabilitation center who were abstinent for 6 days (n = 37), 14 days (n = 33), 1 month (n = 31), 3 months (n = 30), 6 months (n = 26), or 1 year (n = 30) and 39 healthy subjects were administered the Iowa Gambling Task (IGT) to assess decision-making performance. Depression, anxiety, and impulsivity were also examined. One hundred thirty-nine METH abusers who were abstinent for the aforementioned times then underwent a cue session, and subjective and physiological measures were assessed. Results METH dependent individuals who were abstinent for longer periods of time exhibited better decision-making than those who were abstinent for shorter periods of time. And self-reported emotional symptoms improved with abstinence. METH abusers’ ratings of craving decreased with the duration of abstinence, while cue-induced craving increased until 3 months of abstinence and decreased at 6 months and 1 year of abstinence. Conclusions We present time-dependent alterations in decision-making, emotional state, and the incubation of cue-induced craving in METH-dependent individuals, which might have significant clinical implications for the prevention of relapse. PMID:23894345

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

    PubMed Central

    Bharti, Ajay R; Woods, Steven Paul; Ellis, Ronald J; Cherner, Mariana; Rosario, Debra; Potter, Michael; Heaton, Robert K; Everall, Ian P; Masliah, Eliezer; Grant, Igor; Letendre, Scott L

    2016-01-01

    Background Human immunodeficiency virus (HIV) and methamphetamine use commonly affect neurocognitive (NC) functioning. We evaluated the relationships between NC functioning and two fibroblast growth factors (FGFs) in volunteers who differed in HIV serostatus and methamphetamine dependence (MAD). Methods A total of 100 volunteers were categorized into four groups based on HIV serostatus and MAD in the prior year. FGF-1 and FGF-2 were measured in cerebrospinal fluid by enzyme-linked immunosorbent assays along with two reference biomarkers (monocyte chemotactic protein [MCP]-1 and neopterin). Comprehensive NC testing was summarized by global and domain impairment ratings. Results Sixty-three volunteers were HIV+ and 59 had a history of MAD. FGF-1, FGF-2, and both reference biomarkers differed by HIV and MAD status. For example, FGF-1 levels were lower in subjects who had either HIV or MAD than in HIV− and MAD− controls (P=0.003). Multivariable regression identified that global NC impairment was associated with an interaction between FGF-1 and FGF-2 (model R2=0.09, P=0.01): higher FGF-2 levels were only associated with neurocognitive impairment among subjects who had lower FGF-1 levels. Including other covariates in the model (including antidepressant use) strengthened the model (model R2=0.18, P=0.004) but did not weaken the association with FGF-1 and FGF-2. Lower FGF-1 levels were associated with impairment in five of seven cognitive domains, more than FGF-2, MCP-1, or neopterin. Conclusion These findings provide in vivo support that HIV and MAD alter expression of FGFs, which may contribute to the NC abnormalities associated with these conditions. These cross-sectional findings cannot establish causality and the therapeutic benefits of recombinant FGF-1 need to be investigated. PMID:27199571

  4. Neural mechanisms underlying contextual dependency of subjective values: converging evidence from monkeys and humans.

    PubMed

    Abitbol, Raphaëlle; Lebreton, Maël; Hollard, Guillaume; Richmond, Barry J; Bouret, Sébastien; Pessiglione, Mathias

    2015-02-04

    A major challenge for decision theory is to account for the instability of expressed preferences across time and context. Such variability could arise from specific properties of the brain system used to assign subjective values. Growing evidence has identified the ventromedial prefrontal cortex (VMPFC) as a key node of the human brain valuation system. Here, we first replicate this observation with an fMRI study in humans showing that subjective values of painting pictures, as expressed in explicit pleasantness ratings, are specifically encoded in the VMPFC. We then establish a bridge with monkey electrophysiology, by comparing single-unit activity evoked by visual cues between the VMPFC and the orbitofrontal cortex. At the neural population level, expected reward magnitude was only encoded in the VMPFC, which also reflected subjective cue values, as expressed in Pavlovian appetitive responses. In addition, we demonstrate in both species that the additive effect of prestimulus activity on evoked activity has a significant impact on subjective values. In monkeys, the factor dominating prestimulus VMPFC activity was trial number, which likely indexed variations in internal dispositions related to fatigue or satiety. In humans, prestimulus VMPFC activity was externally manipulated through changes in the musical context, which induced a systematic bias in subjective values. Thus, the apparent stochasticity of preferences might relate to the VMPFC automatically aggregating the values of contextual features, which would bias subsequent valuation because of temporal autocorrelation in neural activity.

  5. Association between subjective and cortisol stress response depends on the menstrual cycle phase.

    PubMed

    Duchesne, Annie; Pruessner, Jens C

    2013-12-01

    The relation between the physiologic and subjective stress responses is inconsistently reported across studies. Menstrual cycle phases variations have been found to influence the psychophysiological stress response; however little is known about possible cycle phase differences in the relationship between physiological and subjective stress responses. This study examined the effect of menstrual cycle phase in the association between subjective stress and physiological response. Forty-five women in either the follicular (n=21) or the luteal phase of the menstrual cycle were exposed to a psychosocial stress task. Salivary cortisol, cardiovascular, and subjective stress were assessed throughout the experiment. Results revealed a significant group difference in the association between peak levels of cortisol and post task subjective stress. In women in the follicular phase a negative association was observed (r(2)=0.199, p=0.04), while this relation was positive in the group of women in the luteal phase (r(2)=0.227, p=0.02). These findings suggest a possible role of sex hormones in modulating the cortisol stress response function in emotion regulation.

  6. Methamphetamine causes degeneration of dopamine cell bodies and terminals of the nigrostriatal pathway evidenced by silver staining.

    PubMed

    Ares-Santos, Sara; Granado, Noelia; Espadas, Isabel; Martinez-Murillo, Ricardo; Moratalla, Rosario

    2014-04-01

    Methamphetamine is a widely abused illicit drug. Recent epidemiological studies showed that methamphetamine increases the risk for developing Parkinson's disease (PD) in agreement with animal studies showing dopaminergic neurotoxicity. We examined the effect of repeated low and medium doses vs single high dose of methamphetamine on degeneration of dopaminergic terminals and cell bodies. Mice were given methamphetamine in one of the following paradigms: three injections of 5 or 10 mg/kg at 3 h intervals or a single 30 mg/kg injection. The integrity of dopaminergic fibers and cell bodies was assessed at different time points after methamphetamine by tyrosine hydroxylase immunohistochemistry and silver staining. The 3 × 10 protocol yielded the highest loss of striatal dopaminergic terminals, followed by the 3 × 5 and 1 × 30. Some degenerating axons could be followed from the striatum to the substantia nigra pars compacta (SNpc). All protocols induced similar significant degeneration of dopaminergic neurons in the SNpc, evidenced by amino-cupric-silver-stained dopaminergic neurons. These neurons died by necrosis and apoptosis. Methamphetamine also killed striatal neurons. By using D1-Tmt/D2-GFP BAC transgenic mice, we observed that degenerating striatal neurons were equally distributed between direct and indirect medium spiny neurons. Despite the reduced number of dopaminergic neurons in the SNpc at 30 days after treatment, there was a partial time-dependent recovery of dopamine terminals beginning 3 days after treatment. Locomotor activity and motor coordination were robustly decreased 1-3 days after treatment, but recovered at later times along with dopaminergic terminals. These data provide direct evidence that methamphetamine causes long-lasting loss/degeneration of dopaminergic cell bodies in the SNpc, along with destruction of dopaminergic terminals in the striatum.

  7. Does response interference depend on the subjective visibility of flanker distractors?

    PubMed

    Maniscalco, Brian; Bang, Joo Won; Iravani, Laila; Camps-Febrer, Franc; Lau, Hakwan

    2012-07-01

    Response interference (or response conflict) refers to the phenomenon whereby response times to a target stimulus are longer in the presence of distractor stimuli that indicate contrary motor responses. Response interference has been observed even when the distractor stimuli cannot be discriminated above chance levels. These results raise the question of whether response interference might be driven automatically by the physical distractor stimuli, independently of one's subjective perception of the distractors. Using a modified version of the Eriksen flanker task, we applied metacontrast masks to the flanker stimuli and measured their subjective visibility after each trial. We found converging lines of evidence that the subjective perception of flankers contributed to response interference, over and above the contribution of automatic processing of the stimulus itself. A factorial analysis revealed that the objective, physical congruency of target and flankers and the subjective, perceptual congruency of target and flankers make additive, noninteracting contributions to target response interference, suggesting that the two interference effects originate from independent levels or stages of cognitive processing.

  8. Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion.

    PubMed

    Hess, U S; Whalen, S P; Sandoval, L M; Lynch, G; Gall, C M

    2003-01-01

    It has been proposed that glutamatergic and dopaminergic systems are functionally opposed in their regulation of striatal output. The present study tested the effects of drugs that enhance AMPA-receptor-mediated glutamatergic transmission (ampakines) for their effects on dopamine-related alterations in cortical activity and locomotor behavior. Rats with unilateral 6-hydroxydopamine lesions of the ascending nigro-striatal dopamine system were sensitized to methamphetamine and then tested for methamphetamine-induced circling behavior in the presence and absence of ampakines CX546 and CX614. Both ampakines produced rapid, dose-dependent reductions in circling that were evident within 15 min and sustained through 1 h of behavioral testing. In situ hybridization maps of c-fos mRNA expression showed that in the intact hemisphere, ampakine cotreatment markedly increased c-fos expression in parietal, sensori-motor neocortex above that found in rats treated with methamphetamine alone. Ampakine cotreatment did not augment c-fos expression in frontal, sensori-motor cortex or striatum. Still larger ampakine-elicited effects were obtained in parietal cortex of the dopamine-depleted hemisphere where labeling densities were increased by approximately 60% above values found in methamphetamine-alone rats. With these effects, the hemispheric asymmetry of cortical activation was less pronounced in the ampakine-cotreatment group as compared with the methamphetamine-alone group. These results indicate that positive modulation of AMPA-type glutamate receptors 1) can offset behavioral disturbances arising from sensitized dopamine receptors and 2) increases aggregate neuronal activity in a regionally selective manner that is probably dependent upon behavioral demands.

  9. 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

  10. Methamphetamine and Amphetamine Isomer Concentrations in Human Urine Following Controlled Vicks VapoInhaler Administration

    PubMed Central

    Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; Flegel, Ron; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

    2014-01-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography–mass spectrometry (GC–MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC–MS method with >99% purity of R-(−)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC–MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0–1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT® II Plus, KIMS® II and DRI® had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT® II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation. PMID:25217541

  11. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

    PubMed

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; Flegel, Ron; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-10-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation.

  12. Plasma myeloperoxidase is inversely associated with endothelium-dependent vasodilation in elderly subjects with abnormal glucose metabolism.

    PubMed

    van der Zwan, Leonard P; Teerlink, Tom; Dekker, Jacqueline M; Henry, Ronald M A; Stehouwer, Coen D A; Jakobs, Cornelis; Heine, Robert J; Scheffer, Peter G

    2010-12-01

    Myeloperoxidase (MPO), a biomarker related to inflammation, oxidative stress, and nitric oxide scavenging, has been shown to impair endothelium-dependent vasodilation. Because elevated hydrogen peroxide concentrations in diabetic vessels may enhance MPO activity, we hypothesized that a stronger association of MPO with flow-mediated dilation (FMD) may be found in subjects with abnormal glucose metabolism. Myeloperoxidase concentrations were measured in EDTA plasma samples from participants of a population-based cohort study, including 230 subjects with normal glucose metabolism and 386 with abnormal glucose metabolism. Vascular function was expressed as FMD and nitroglycerin-mediated dilation of the brachial artery. In subjects with abnormal glucose metabolism, MPO was negatively associated with FMD (-20.9 [95% confidence interval {CI}, -41.7 to -0.2] -μm change in FMD per SD increment of MPO). This association remained significant after adjustment for nitroglycerin-mediated dilation (-31.1 [95% CI, -50.0 to -12.3]) and was not attenuated after further adjustment for established risk factors. In subjects with normal glucose metabolism, MPO was not significantly associated with FMD (2.0 [95% CI, -16.0 to 20.0]). In conclusion, in subjects with abnormal glucose metabolism, plasma levels of MPO are inversely associated with endothelium-dependent vasodilation, possibly reflecting enhancement of MPO activity by vascular oxidative stress.

  13. [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.

  14. 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…

  15. 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.

  16. 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, ...

  17. 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

  18. 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.

  19. Maternal separation fails to render animals more susceptible to methamphetamine-induced conditioned place preference.

    PubMed

    Faure, Jacqueline; Stein, Dan J; Daniels, William

    2009-12-01

    The maternal separation (MS) paradigm is an animal model that has been successfully used to study the long term effects of child abuse and neglect. Experiments showed that animals subjected to trauma and stress early in life display behavioural, endocrinological and growth factor abnormalities at a later stage in life, results that mirrored clinical conditions. It is apparent that adverse events early in life may affect the development and maturation of the brain negatively. The purpose of the present study was to investigate whether the abnormal brain development occurring in separated animals would also enhance the development of a preference for psychostimulant drug usage. Rats were subjected to maternal deprivation and further exposed to methamphetamine-induced conditioned place preference (CPP) which primarily measures drug reward (ventral striatum) learning and memory. Apomorphine-induced locomotor activity was also assessed to investigate the effects of methamphetamine on the dorsal (primarily locomotor activity) striatal dopaminergic system. We found that four consecutive injections of methamphetamine resulted in CPP behaviour 24 h after the 4th injection. A further four injections yielded similar CPP results and this effect lasted for at least 7 days until the third CPP assessment. These animals also had decreased ACTH and corticosterone secretions, but the prolactin levels were increased. Prior exposure to maternal separation did not have any effect on the CPP test. The ACTH and corticosterone secretions were also similarly reduced. However maternal separation decreased the release of prolactin and this reduction was not evident in the separated group that received methamphetamine. There was no significant difference in the apomorphine-induced locomotor activity of normally reared animals whether they received methamphetamine or saline. Interestingly there was a significant difference in locomotor activity between the two groups of animals that were

  20. Imbalanced Functional Link between Valuation Networks in Abstinent Heroin-Dependent Subjects

    PubMed Central

    Xie, Chunming; Shao, Yongcong; Ma, Lin; Zhai, Tianye; Ye, Enmao; Fu, Liping; Bi, Guohua; Chen, Gang; Cohen, Alex; Li, Wenjun; Chen, Guangyu; Yang, Zheng; Li, Shi-Jiang

    2015-01-01

    Using neuroeconomic approaches, our findings demonstrate that the underlying duality of the β-δ discounting networks that jointly influence valuation is impaired to a pathogenic state in abstinent heroin dependents. The imbalanced functional link between the β-δ networks for valuation may orchestrate the irrational choice in drug addiction. PMID:23207652

  1. Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections.

    PubMed

    Zhou, Tianyan; Huang, Chaoqun; Chen, Yue; Xu, Jiaojiao; Shanbhag, Preeti Devaraya; Chen, Guangping

    2013-01-01

    Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds. rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds. In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum. After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus. After 7 days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions. Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level. Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus. rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner. rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections. Induction activity of methamphetamine is in the order of cerebellum>frontal cortex, hippocampus>striatum. These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.

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

    PubMed

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

    2011-08-01

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

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

    PubMed Central

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

    2013-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered at PND90. Mechanisms underlying this “resistance” were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. PMID:21190217

  4. Simulation of electron dynamics subject to intense laser fields using a time-dependent Volkov basis

    NASA Astrophysics Data System (ADS)

    Covington, Cody; Kidd, Daniel; Gilmer, Justin; Varga, Kálmán

    2017-01-01

    We present various intense laser-driven electron dynamics simulations performed using a Volkov basis set and compare results with other popular choices of basis. The Volkov basis is comprised of plane waves modified by a time-dependent phase factor, allowing for improved accuracy over other representations such as a real-space grid or plane-wave basis. Alternatively, this advantage may be realized by being afforded significantly larger time-step sizes in wave-function propagation techniques. Comparisons of the Volkov basis set to other popular bases have been carried out for model one-dimensional finite and periodic systems as well as three-dimensional systems using time-dependent density functional theory, and the efficiency and accuracy of the Volkov approach have been demonstrated.

  5. 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.

  6. Cardiomyopathy associated with the smoking of crystal methamphetamine.

    PubMed

    Hong, R; Matsuyama, E; Nur, K

    1991-03-06

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

  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. Tracking irregular morphophonological dependencies in natural language: evidence from the acquisition of subject-verb agreement in French.

    PubMed

    Nazzi, Thierry; Barrière, Isabelle; Goyet, Louise; Kresh, Sarah; Legendre, Géraldine

    2011-07-01

    This study examines French-learning infants' sensitivity to grammatical non-adjacent dependencies involving subject-verb agreement (e.g., le/les garçons lit/lisent 'the boy(s) read(s)') where number is audible on both the determiner of the subject DP and the agreeing verb, and the dependency is spanning across two syntactic phrases. A further particularity of this subsystem of French subject-verb agreement is that number marking on the verb is phonologically highly irregular. Despite the challenge, the HPP results for 24- and 18-month-olds demonstrate knowledge of both number dependencies: between the singular determiner le and the non-adjacent singular verbal forms and between the plural determiner les and the non-adjacent plural verbal forms. A control experiment suggests that the infants are responding to known verb forms, not phonological regularities. Given the paucity of such forms in the adult input documented through a corpus study, these results are interpreted as evidence that 18-month-olds have the ability to extract complex patterns across a range of morphophonologically inconsistent and infrequent items in natural language.

  10. Molecular structure-dependent deformations in boron nitride nanostructures subject to an electrical field

    NASA Astrophysics Data System (ADS)

    Zhang, Jin; Wang, Chengyuan; Adhikari, Sondipon

    2013-06-01

    Based on a molecular mechanics approach pre-buckling and buckling deformations are studied for boron nitride nanotubes (BNNTs) and nanosheets (BNNSs) subject to an electrical field. Due to the reverse piezoelectric effect a compressive or shear force is generated for those of zigzag and armchair structures, respectively. As a result, axial deformation and buckling occur for zigzag BNNTs and BNNSs, while a torsional or shear deformation occurs for their armchair counterparts, followed by the corresponding buckling. The critical buckling electrical field is also studied and found to decrease as the aspect ratio of BNNTs and BNNSs increases. Such an effect of the aspect ratio turns out to be more pronounced for the buckling of armchair BNNTs and BNNSs.

  11. Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence.

    PubMed

    Iudicello, Jennifer E; Woods, Steven P; Vigil, Ofilio; Scott, J Cobb; Cherner, Mariana; Heaton, Robert K; Atkinson, J Hampton; Grant, Igor

    2010-08-01

    Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way of data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent, and 58 used MA at least once during the interval period. A total of 38 non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long-term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use MA were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities than the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.

  12. Methamphetamine laboratory explosions: a new and emerging burn injury.

    PubMed

    Santos, Ariel P; Wilson, Ashley K; Hornung, Carlton A; Polk, Hiram C; Rodriguez, Jorge L; Franklin, Glen A

    2005-01-01

    The proliferation of clandestine methamphetamine laboratories (meth labs) as a result of the growing popularity of the drug has resulted in an increasing incidence of burn injuries associated with laboratory accidents. We undertook this study to characterize these injuries. Fifteen consecutive patients were identified and case-matched by age and TBSA to 45 control subjects. Most meth lab patients were men, Caucasian, unemployed, and positive for polysubstance abuse. Resuscitation requirements were 1.8 times greater in these patients. There was a higher incidence of inhalational injury corresponding to higher intubation and tracheostomy rate and longer ventilator days among meth lab patients. The rate of nosocomial pneumonia, skin graft loss, and mortality were not different between the two groups. Meth lab injury is unique and requires more critical care resources. It also is associated with lack of insurance coverage and poor follow-up after injury. This injury has a significant impact not only on patients but also on the healthcare system.

  13. Is brain gliosis a characteristic of chronic methamphetamine use in the human?

    PubMed

    Tong, Junchao; Fitzmaurice, Paul; Furukawa, Yoshiaki; Schmunk, Gregory A; Wickham, Dennis J; Ang, Lee-Cyn; Sherwin, Allan; McCluskey, Tina; Boileau, Isabelle; Kish, Stephen J

    2014-07-01

    Animal data show that high doses of the stimulant drug methamphetamine can damage brain dopamine neurones; however, it is still uncertain whether methamphetamine, at any dose, is neurotoxic to human brain. Since gliosis is typically associated with brain damage and is observed in animal models of methamphetamine exposure, we measured protein levels (intact protein and fragments, if any) of markers of microgliosis (glucose transporter-5, human leukocyte antigens HLA-DRα [TAL.1B5] and HLA-DR/DQ/DPβ [CR3/43]) and astrogliosis (glial fibrillary acidic protein, vimentin, and heat shock protein-27) in homogenates of autopsied brain of chronic methamphetamine users (n=20) and matched controls (n=23). Intact protein levels of all markers were, as expected, elevated (+28%-1270%, P<0.05) in putamen of patients with the neurodegenerative disorder multiple system atrophy (as a positive control) as were concentrations of fragments of glial fibrillary acidic protein, vimentin and heat shock protein-27 (+170%-4700%, P<0.005). In contrast, intact protein concentrations of the markers were normal in dopamine-rich striatum (caudate, putamen) and in the frontal cortex of the drug users. However, striatal levels of cleaved vimentin and heat shock protein-27 were increased (by 98%-211%, P<0.05), with positive correlations (r=0.41-0.60) observed between concentrations of truncated heat shock protein-27 and extent of dopamine loss (P=0.006) and levels of lipid peroxidation products 4-hydroxynonenal (P=0.046) and malondialdehyde (P=0.11). Our failure to detect increased intact protein levels of commonly used markers of microgliosis and astrogliosis could be explained by exposure to methamphetamine insufficient to cause a toxic process associated with overt gliosis; however, about half of the subjects had died of drug intoxication suggesting that "high" drug doses might have been used. Alternatively, drug tolerance to toxic effects might have occurred in the subjects, who were all

  14. Membrane integrity of Campylobacter jejuni subjected to high pressure is pH-dependent

    NASA Astrophysics Data System (ADS)

    Lerasle, M.; Guillou, S.; Simonin, H.; Laroche, M.; de Lamballerie, M.; Federighi, M.

    2012-03-01

    Our study focuses on a foodborne pathogen, Campylobacter, which is responsible for the most frequent bacterial enteritis worldwide. Membrane integrity of Campylobacter jejuni NCTC 11168 cells treated at high pressure (300 MPa, 20°C, 10 min) at pH 7.0 and pH 5.6 was measured by fluorescence spectroscopy of propidium iodide (PI) uptake. The percentage of membrane-damaged cells by high pressure, in which PI is allowed to penetrate, was determined using two calibration methods based on the PI fluorescence signal obtained with cells killed either by a heat treatment (80°C for 15 min) or by a pressure treatment (400 MPa, 20°C, 10 min). Both calibrations were shown to be statistically different (P<0.05), particularly at acidic pH, suggesting that a difference in the penetration of PI into bacterial cells might depend on the mode of cell inactivation. These results corroborate the fact that the mechanism of microbial inactivation by high pressure is pH-dependent.

  15. 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.

  16. Family-supportive supervisor behaviors, work engagement, and subjective well-being: a contextually dependent mediated process.

    PubMed

    Matthews, Russell A; Mills, Maura J; Trout, Rachel C; English, Lucy

    2014-04-01

    Grounded in a multistudy framework, we examined the relationship between family-supportive supervisor behaviors, work engagement, and subjective well-being as a contextually dependent mediated process. In Study 1 (N = 310), based on broaden-and-build and conservation of resources theories, we tested the proposed mediated process while controlling for perceived organizational support and perceived managerial effectiveness. We also demonstrated that family-supportive supervisor behaviors are distinguishable from general supervisor behaviors. In Study 2 (N = 1,640), using multigroup structural equation modeling, we validated and extended Study 1 results by examining how the mediated model varied based on 2 contextualizing constructs: (a) dependent care responsibilities and (b) availability of family-friendly benefits. Although the mediational results were contextually dependent, they were not necessarily consistent with hypothesizing based on conservation of resources theory. Practical implications are emphasized in addition to future research directions.

  17. An exact solution for the history-dependent material and delamination behavior of laminated plates subjected to cylindrical bending

    SciTech Connect

    Williams, Todd O

    2009-01-01

    The exact solution for the history-dependent behavior of laminated plates subjected to cylindrical bending is presented. The solution represents the extension of Pagano's solution to consider arbitrary types of constitutive behaviors for the individual lamina as well as arbitrary types of cohesive zones models for delamination behavior. Examples of the possible types of material behavior are plasticity, viscoelasticity, viscoplasticity, and damaging. Examples of possible CZMs that can be considered are linear, nonlinear hardening, as well as nonlinear with softening. The resulting solution is intended as a benchmark solution for considering the predictive capabilities of different plate theories. Initial results are presented for several types of history-dependent material behaviors. It is shown that the plate response in the presence of history-dependent behaviors can differ dramatically from the elastic response. These results have strong implications for what constitutes an appropriate plate theory for modeling such behaviors.

  18. Cardiovascular/non-insulin-dependent diabetes mellitus risk factors and intramyocellular lipid in healthy subjects: a sex comparison.

    PubMed

    White, Lesley J; Ferguson, Michael A; McCoy, Sean C; Kim, Hee-Won; Castellano, Vanessa

    2006-01-01

    Little is known about the relationship between intramyocellular lipid (IMCL) and coronary artery disease (CAD)/non-insulin-dependent diabetes mellitus risk factors. The aim of the study was to examine the relationship between IMCL and CAD/non-insulin-dependent diabetes mellitus risk factors in healthy male (n = 9) and female (n = 10) subjects with similar norm-based aerobic fitness and body composition. Nineteen volunteers (21-36 years) completed health and physical activity questionnaires, cardiovascular and body composition evaluation, and assessment of thigh IMCL using proton magnetic resonance spectroscopy. Outcome measures were blood pressure, total cholesterol, high-density lipoprotein cholesterol, C-reactive protein, interleukin 6, tumor necrosis factor alpha (TNF-alpha), homocysteine, insulin resistance (IR), percentage of body fat, waist-to-hip ratio, physical activity levels, and cardiovascular fitness. Analysis of variance was used for group comparisons. Correlation analyses were used to determine association between variables, and stepwise regression was used to determine predictive variables of IR. Women had 2-fold higher IMCL and greater IR than men (P < .05). Men had greater plasma homocysteine and interleukin 6 concentration (P < .05) as well as stronger correlations with CAD risk factors than female subjects. Correlation analyses using all subjects revealed a significant relationship between IMCL and waist-to-hip ratio, body weight, percentage of body fat, and IR. In the regression analysis, age, IMCL, and TNF-alpha were the strongest predictors of IR (R2 = 0.62, P < .01). Our results suggest that female subjects, matched for age and fitness, have higher IMCL compared with their male counterparts. IMCL was correlated with several CAD and prediabetes markers in both male and female subjects. In the final regression model, age, IMCL, and TNF-alpha were the strongest predictors of IR. Future studies with larger sample sizes are warranted.

  19. A comparison of impulsivity, depressive symptoms, lifetime stress and sensation seeking in healthy controls versus participants with cocaine or methamphetamine use disorders.

    PubMed

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

    2015-01-01

    Previous research has focused on developing theories of addiction that may explain behavior in cocaine- and methamphetamine-dependent individuals. The primary goal of this report was to compare and contrast the prevalence of self-reported measures of impulsivity, depression, lifetime stress and sensation-seeking in healthy controls versus individuals with cocaine or methamphetamine use disorders. Twenty-nine individuals with cocaine use disorders and 31 individuals with methamphetamine use disorders were matched with 31 healthy control participants on several demographic variables. All participants were administered behavioral questionnaires including the Barrett Impulsiveness Scale (assessing impulsivity), Beck Depression Inventory II (assessing depression), Life Stressor Checklist-Revised (assessing lifetime stress) and the Impulsive Sensation Seeking Scale (assessing sensation-seeking). When compared to healthy controls, individuals with cocaine and methamphetamine use disorders had significantly higher levels of impulsivity and sensation-seeking. In addition, when compared to healthy controls, individuals with cocaine use disorders had significantly higher Beck Depression Inventory II scores, while individuals with methamphetamine use disorders had significantly higher Life Stressor Checklist-Revised scores. The results revealed that there were significantly higher levels of impulsivity, depression and sensation-seeking in cocaine users and significantly higher impulsivity, lifetime stress and sensation-seeking in methamphetamine users when compared to healthy controls.

  20. Ceftriaxone upregulates the glutamate transporter in medial prefrontal cortex and blocks reinstatement of methamphetamine seeking in a condition place preference paradigm

    PubMed Central

    Abulseoud, Osama A.; Miller, Joseph D.; Wu, Jinhua; Choi, Doo-Sup; Holschneider, Daniel P.

    2014-01-01

    Glutamate signaling plays an essential role in drug-seeking behavior. Using reinstatement of conditioned place preference (CPP), we determined whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of the glutamate transporter (EAAT2) on glial cells, blocks methamphetamine-triggered reinstatement of CPP. Rats acquired methamphetamine CPP following 7 consecutive days of conditioning, during which each animal received pairings of alternating morning methamphetamine (2.5 mg/kg, IP) and afternoon saline (IP). Animals showing CPP were successfully extinguished with repeated twice daily saline administration over a 7-day period. Ceftriaxone (200 mg/kg, IP) was administered (vs. saline) once a day for 7 days during the extinction period. Upon successful extinction, animals received a single dose of methamphetamine (2.5 mg/kg, IP) for reinstatement and were tested for CPP one day later. Using real time PCR, EAAT2 mRNA levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were quantified in response to ceftriaxone. Ceftriaxone blocked methamphetamine-triggered reinstatement of CPP and significantly increased EAAT2 mRNA levels in the mPFC, with a trend towards significance in the NAc. In conclusion, Ceftriaxone modulated the expression of the glutamate transporter in a critical region of the cortico-striatal addiction circuitry and attenuated drug-seeking behavior in rats. Further research is needed to test the efficacy of compounds targeting the EAAT2 in human methamphetamine-dependent users. PMID:22521042

  1. 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

  2. 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.

  3. 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

  4. A reanalysis of McGurk data suggests that audiovisual fusion in speech perception is subject-dependent.

    PubMed

    Schwartz, Jean-Luc

    2010-03-01

    Audiovisual perception of conflicting stimuli displays a large level of intersubject variability, generally larger than pure auditory or visual data. However, it is not clear whether this actually reflects differences in integration per se or just the consequence of slight differences in unisensory perception. It is argued that the debate has been blurred by methodological problems in the analysis of experimental data, particularly when using the fuzzy-logical model of perception (FLMP) [Massaro, D. W. (1987). Speech Perception by Ear and Eye: A Paradigm for Psychological Inquiry (Laurence Erlbaum Associates, London)] shown to display overfitting abilities with McGurk stimuli [Schwartz, J. L. (2006). J. Acoust. Soc. Am. 120, 1795-1798]. A large corpus of McGurk data is reanalyzed, using a methodology based on (1) comparison of FLMP and a variant with subject-dependent weights of the auditory and visual inputs in the fusion process, weighted FLMP (WFLMP); (2) use of a Bayesian selection model criterion instead of a root mean square error fit in model assessment; and (3) systematic exploration of the number of useful parameters in the models to compare, attempting to discard poorly explicative parameters. It is shown that WFLMP performs significantly better than FLMP, suggesting that audiovisual fusion is indeed subject-dependent, some subjects being more "auditory," and others more "visual." Intersubject variability has important consequences for theoretical understanding of the fusion process, and re-education of hearing impaired people.

  5. Dynamic Creep Buckling: Analysis of Shell Structures Subjected to Time-dependent Mechanical and Thermal Loading

    NASA Technical Reports Server (NTRS)

    Simitses, G. J.; Carlson, R. L.; Riff, R.

    1985-01-01

    The objective of the present research is to develop a general mathematical model and solution methodologies for analyzing the structural response of thin, metallic shell structures under large transient, cyclic, or static thermomechanical loads. Among the system responses associated with these loads and conditions are thermal buckling, creep buckling, and ratcheting. Thus geometric and material nonlinearities (of high order) can be anticipated and must be considered in developing the mathematical model. A complete, true ab-initio rate theory of kinematics and kinetics for continuum and curved thin structures, without any restriction on the magnitude of the strains or the deformations, was formulated. The time dependence and large strain behavior are incorporated through the introduction of the time rates of metric and curvature in two coordinate systems: fixed (spatial) and convected (material). The relations between the time derivative and the covariant derivative (gradient) were developed for curved space and motion, so the velocity components supply the connection between the equations of motion and the time rates of change of the metric and curvature tensors.

  6. Impaired time perception and motor timing in stimulant-dependent subjects.

    PubMed

    Wittmann, Marc; Leland, David S; Churan, Jan; Paulus, Martin P

    2007-10-08

    Stimulant-dependent individuals (SDI) have abnormal brain metabolism and structural changes involving dopaminergic target areas important for the processing of time. These individuals are also more impulsive and impaired in working memory and attention. The current study tested whether SDI show altered temporal processing in relation to impulsivity or impaired prefrontal cortex functioning. We employed a series of timing tasks aimed to examine time processing from the milliseconds to multiple seconds range and assessed cognitive function in 15 male SDI and 15 stimulant-naïve individuals. A mediation analysis determined the degree to which impulsivity or executive dysfunctions contributed to group differences in time processing. SDI showed several abnormal time processing characteristics. SDI needed larger time differences for effective duration discrimination, particularly for intervals of around 1s. SDI also accelerated finger tapping during a continuation period after a 1Hz pacing stimulus was removed. In addition, SDI overestimated the duration of a relatively long time interval, an effect which was attributable to higher impulsivity. Taken together, these data show for the first time that SDI exhibit altered time processing in several domains, one which can be explained by increased impulsivity. Altered time processing in SDI could explain why SDI have difficulty delaying gratification.

  7. Serum withdrawal potentiates the toxic effects of methamphetamine in vitro.

    PubMed

    Cadet, J L; Ordonez, S

    2000-09-01

    Methamphetamine (METH) has been shown to cause neurotoxic damage both in vitro and in vivo. The mechanisms of action are thought to involve the production of pathophysiologic concentration of free radicals. The present study was undertaken to assess the toxic effects of METH caused dose-dependent increased production of reactive oxygen species (ROS) and cell death. Cell death caused by METH was characterized by cytoplasmic vacuolar formation, shrinkage of cytoplasm and nuclear dissolution. Flow cytometric evaluation also revealed that this toxin causes changes similar to those observed in cells undergoing apoptosis. When taken together these observations suggest the METH can cause these cells to die via apoptosis. Further experiments indicated that growth of these cells in low (1%) serum or in the absence of serum markedly enhanced the apoptotic effects of METH. These data provide further support for the ideas that METH can cause ROS-mediated apoptosis.

  8. 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

  9. 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

  10. Methamphetamine drinking microstructure in mice bred to drink high or low amounts of methamphetamine.

    PubMed

    Eastwood, Emily C; Barkley-Levenson, Amanda M; Phillips, Tamara J

    2014-10-01

    Genetic factors likely influence individual sensitivity to positive and negative effects of methamphetamine (MA) and risk for MA dependence. Genetic influence on MA consumption has been confirmed by selectively breeding mouse lines to consume high (MAHDR) or low (MALDR) amounts of MA, using a two-bottle choice MA drinking (MADR) procedure. Here, we employed a lickometer system to characterize the microstructure of MA (20, 40, and 80mg/l) and water intake in MAHDR and MALDR mice in 4-h limited access sessions, during the initial 4hours of the dark phase of their 12:12h light:dark cycle. Licks at one-minute intervals and total volume consumed were recorded, and bout analysis was performed. MAHDR and MALDR mice consumed similar amounts of MA in mg/kg on the first day of access, but MAHDR mice consumed significantly more MA than MALDR mice during all subsequent sessions. The higher MA intake of MAHDR mice was associated with a larger number of MA bouts, longer bout duration, shorter interbout interval, and shorter latency to the first bout. In a separate 4-h limited access MA drinking study, MALDR and MAHDR mice had similar blood MA levels on the first day MA was offered, but MAHDR mice had higher blood MA levels on all subsequent days, which corresponded with MA intake. These data provide insight into the microstructure of MA intake in an animal model of differential genetic risk for MA consumption, which may be pertinent to MA use patterns relevant to genetic risk for MA dependence.

  11. Methamphetamine drinking microstructure in mice bred to drink high or low amounts of methamphetamine

    PubMed Central

    Eastwood, Emily C.; Barkley-Levenson, Amanda M.; Phillips, Tamara J.

    2014-01-01

    Genetic factors likely influence individual sensitivity to positive and negative effects of methamphetamine (MA) and risk for MA dependence. Genetic influence on MA consumption has been confirmed by selectively breeding mouse lines to consume high (MAHDR) or low (MALDR) amounts of MA, using a two-bottle choice MA drinking (MADR) procedure. Here, we employed a lickometer system to characterize the microstructure of MA (20, 40, and 80 mg/l) and water intake in MAHDR and MALDR mice in 4-h limited access sessions, during the initial 4 hours of the dark phase of their 12:12 h light:dark cycle. Licks at one-minute intervals and total volume consumed were recorded, and bout analysis was performed. MAHDR and MALDR mice consumed similar amounts of MA in mg/kg on the first day of access, but MAHDR mice consumed significantly more MA than MALDR mice during all subsequent sessions. The higher MA intake of MAHDR mice was associated with a larger number of MA bouts, longer bout duration, shorter interbout interval, and shorter latency to the first bout. In a separate 4-h limited access MA drinking study, MALDR and MAHDR mice had similar blood MA levels on the first day MA was offered, but MAHDR mice had higher blood MA levels on all subsequent days, which corresponded with MA intake. These data provide insight into the microstructure of MA intake in an animal model of differential genetic risk for MA consumption, which may be pertinent to MA use patterns relevant to genetic risk for MA dependence. PMID:24978098

  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. One-trial behavioral sensitization in preweanling rats: differential effects of cocaine, methamphetamine, methylphenidate, and D-amphetamine

    PubMed Central

    Kozanian, Olga O.; Greenfield, Venuz Y.; Horn, Leslie R.; Gutierrez, Arnold; Mohd-Yusof, Alena; Castellanos, Kevin A.

    2011-01-01

    Rationale Preweanling rats exhibit robust one-trial cocaine-induced behavioral sensitization; however, it is uncertain whether other psychostimulants can also induce sensitization in young rats using the one-trial procedure. Objective The purpose of this study was to determine whether methamphetamine, methylphenidate, and D-amphetamine are capable of inducing one-trial locomotor sensitization in preweanling rats. Methods In a series of four experiments, rats were pretreated with cocaine (30 mg/kg), methamphetamine (2–12 mg/kg), methylphenidate (5–20 mg/kg), or amphetamine (5 mg/kg) before being placed in a novel activity chamber or the home cage on PD 19. Rats were then challenged with the same psychostimulant (20 mg/kg cocaine, 1–8 mg/kg methamphetamine, 2.5–7.5 mg/kg methylphenidate, or 1–2 mg/kg amphetamine) on PD 21, with distance traveled being measured for 180 min. In a separate experiment, rats were pretreated with methamphetamine on PD 16–19 and challenged with methamphetamine on PD 21. Results Only cocaine, but not various dose combinations of other psychostimulants, was able to produce one-trial behavioral sensitization in preweanling rats. Context-dependent locomotor sensitization was also evident if rats were pretreated with methamphetamine on PD 16–19 and tested on PD 21. Conclusions It is uncertain why only cocaine was able to induce one-trial locomotor sensitization in preweanling rats, but it is possible that: (a) the neural circuitry mediating sensitization differs according to psychostimulant, (b) cocaine is more readily associated with environmental contexts than other psychostimulants, or (c) affinity and pharmacokinetic factors may underlie cocaine’s ability to induce one-trial behavioral sensitization in preweanling rats. PMID:21537939

  14. Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report

    PubMed Central

    Breen, M S; Uhlmann, A; Nday, C M; Glatt, S J; Mitt, M; Metsalpu, A; Stein, D J; Illing, N

    2016-01-01

    The clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA; N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies including CLN3, FBP1, TBC1D2 and ZNF821 (RNA degradation), ELK3 and SINA3 (circadian clock) and PIGF and

  15. Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report.

    PubMed

    Breen, M S; Uhlmann, A; Nday, C M; Glatt, S J; Mitt, M; Metsalpu, A; Stein, D J; Illing, N

    2016-05-10

    The clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA; N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies including CLN3, FBP1, TBC1D2 and ZNF821 (RNA degradation), ELK3 and SINA3 (circadian clock) and PIGF and

  16. 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.

  17. 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

  18. A tryptamine-derived catecholaminergic enhancer, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], attenuates reinstatement of methamphetamine-seeking behavior in rats.

    PubMed

    Hiranita, T; Yamamoto, T; Nawata, Y

    2010-01-20

    Relapse to drug craving is problematic in treatment for drug abuse. Evidence suggests inactivation of dopaminergic neurotransmission during drug withdrawal. Meanwhile, a tryptamine analogue, (-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP], has been reported to enhance electrical stimulation of monoamine release. This study examined the effect of (-)-BPAP on reinstatement of methamphetamine-seeking behavior in an animal model of relapse to drug abuse. Rats were trained to i.v. self-administer methamphetamine paired with a light and tone (methamphetamine-associated cues) under a fixed-ratio 1 schedule of reinforcement for 10 days. After extinction session under saline infusions without cues, a reinstatement test under saline infusions was begun. Reinstatement induced by methamphetamine-associated cues or methamphetamine-priming injections was attenuated by repeated administration of (-)-BPAP during the extinction phase. Acute administration of (-)-BPAP on test day dose-dependently attenuated both reinstatements. Acute administration of (-)-BPAP neither reinstated methamphetamine-seeking behavior alone nor affected methamphetamine self-administration. Pretreatment with either R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH-23390), a dopamine D(1)-like receptor antagonist, or amisulpride, a dopamine D(2)-like receptor antagonist, did not appreciably affected the acute effect of (-)-BPAP on both reinstatements. Co-pretreatment with the dopamine receptor antagonists failed to alter the effects of (-)-BPAP. Meanwhile, pretreatment with a dopamine D(1)-like receptor agonist, (+/-)-6-chloro-7,8-dihydroxy-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297), dose-dependently attenuated reinstatement induced by the cues or methamphetamine-priming injections. In contrast to (-)-BPAP, pretreatment with SCH-23390 reversed the effects of SKF-81297. Our findings suggest activation of dopamine D(1)-like receptors results

  19. 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.

  20. Reduced anterior corpus callosum white matter integrity is related to increased impulsivity and reduced discriminability in cocaine-dependent subjects: diffusion tensor imaging.

    PubMed

    Moeller, Frederick Gerard; Hasan, Khader M; Steinberg, Joel L; Kramer, Larry A; Dougherty, Donald M; Santos, Rafael M; Valdes, Ignacio; Swann, Alan C; Barratt, Ernest S; Narayana, Ponnada A

    2005-03-01

    Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocaine-dependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocaine-dependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocaine-dependent subjects.

  1. 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…

  2. 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…

  3. 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…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  5. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methamphetamine test system. 862.3610 Section 862...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems §...

  6. 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…

  7. 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.

  8. When treatment meets research: clinical perspectives from the CSAT Methamphetamine Treatment Project.

    PubMed

    Obert, Jeanne L; Brown, Alison Hamilton; Zweben, Joan; Christian, Darrell; Delmhorst, Jenn; Minsky, Sam; Morrisey, Patrick; Vandersloot, Denna; Weiner, Ahndrea

    2005-04-01

    Integrating research-based treatments into clinical settings has become a priority in the substance abuse treatment field. This article examines the introduction of research, via manualized treatment (i.e., the Matrix Model), into community treatment settings that participated in the Center for Substance Abuse Treatment Methamphetamine Treatment Project, a multi-site randomized controlled trial (RCT) that provided free treatment to 1016 methamphetamine-dependent individuals. With both empirical (qualitative) and anecdotal data from those involved clinically in the project, the article utilizes the framework of practitioner concerns set forth by Addis, Wade, and Hatgis (1999) to assess the issues realized during the implementation of this manualized treatment. Despite fairly smooth implementation of the model, the authors conclude that introducing manualized treatment in the context of an RCT may not be the best way to bring research-based treatment into the practice world.

  9. Acute exercise ameliorates craving and inhibitory deficits in methamphetamine: An ERP study.

    PubMed

    Wang, Dongshi; Zhou, Chenglin; Chang, Yu-Kai

    2015-08-01

    This study aimed to determine the effect of acute exercise in the potential context of non-pharmacological intervention for methamphetamine (MA)-related craving; we additionally determine its effect on the inhibitory control induced by standard and MA-related tasks according to behavioral and neuroelectric measurements among MA-dependent individuals. The present study employed a within-subjects, counterbalanced design. A total of 24 participants who met the DSM-IV criteria for MA dependence were recruited. The craving level, reaction time, and response accuracy, as well as the event-related potential (ERP) components N2 and P3, were measured following exercise and the control treatment in a counterbalanced order. The exercise session consisted of an acute stationary cycle exercise at a moderate intensity, whereas the control treatment consisted of an active reading session. The self-reported MA craving was significantly attenuated during, immediately following, and 50min after the exercise session compared with the pre-exercise ratings, whereas the craving scores at these time points following exercise were lower than those for the reading control session. Acute exercise also facilitated inhibitory performance in both the standard and MA-related Go/Nogo tasks. A larger N2 amplitude, but not a larger P3 amplitude, was observed during both tasks in the exercise session and the Nogo condition compared with the reading control session and the Go condition. This is the first empirical study to demonstrate these beneficial effects of acute aerobic exercise at a moderate intensity on MA-related craving and inhibitory control in MA-dependent individuals. These results suggest a potential role for acute aerobic exercise in treating this specific type of substance abuse.

  10. 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.

  11. Experimentally induced aggressiveness in heroin-dependent patients treated with buprenorphine: comparison of patients receiving methadone and healthy subjects.

    PubMed

    Gerra, Gilberto; Zaimovic, Amir; Raggi, Maria Augusta; Moi, Gabriele; Branchi, Barbara; Moroni, Mirko; Brambilla, Francesca

    2007-01-15

    Objective measures of experimentally induced aggressiveness were evaluated in heroin-dependent patients (HDP), 15 receiving buprenorphine (BUP) and 15 receiving methadone (METH) treatment. HDP were randomly assigned to BUP and METH groups. Fifteen healthy subjects (CONT) were included in the study as controls. During a laboratory task, the Point Subtraction Aggression Paradigm, subjects earned monetary reinforcement and could respond by ostensibly subtracting money from a fictitious subject (the aggressive response). Money-earning (points maintained) responses did not differ in BUP patients and in controls. In contrast, point-maintained responses were significantly lower in the group of HDP treated with METH than in both the BUP and CONT groups. Aggressive responses were significantly higher in the HDP group than in the CONT group. No significant differences in aggressive responses were found between the BUP and METH groups. Baseline concentrations of plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) were higher in HDP than in CONT. During the experimental task, ACTH and CORT increased significantly less in METH patients than in BUP patients and CONT. Norepinephrine (NE) and epinephrine (EPI) levels increased significantly more in HDP than in CONT, without any difference between the METH and BUP patients. PSAP aggressive responses positively correlated with NE and EPI changes, as well as with Buss-Durkee Hostility Inventory (BDHI) scores in both METH and BUP patients and also in CONT subjects. No correlation was found between the extent of heroin exposure, drug doses and aggressiveness levels. BUP, similarly to METH, does not seem to affect outward-directed aggressiveness, as aggressive responses related more to monoamine levels and personality traits than to the action of opioid agonists. Money-earning responses seemed to be unimpaired in BUP patients.

  12. Investigating Methamphetamine Craving Using the Extinction-Reinstatement Model in the Rat

    PubMed Central

    Kufahl, Peter R.; Olive, M. Foster

    2012-01-01

    Summary Like all other drugs of abuse, the primary therapeutic objective for treating methamphetamine addiction research is the maintenance of abstinence and prevention of relapse to habitual drug-taking. Compounds with the potential to prevent relapse are often investigated in rats that are trained to self-administer intravenous methamphetamine, subjected to extinction training where responding is no longer reinforced, and then given tests for reinstatement of drug-seeking behavior triggered by methamphetamine injections or re-exposure to drug-paired cues. Experimental compounds are administered to the animals prior to the reinstatement tests to evaluate their potential for attenuating or preventing drug-seeking behavior. This article describes the common procedures of the extinction-reinstatement model in studies of this type, and identifies areas of discrepancy. This is followed by a comprehensive overview of the currently published anti-reinstatement effects of pharmacological compounds, classified by the most relevant neurological systems associated with these compounds. The article concludes with a brief discussion of how the study of anti-reinstatement effects can be expanded to further verify existing positive results or to find novel neurobiological targets. PMID:22428089

  13. Failure of baclofen to modulate discriminative-stimulus effects of cocaine or methamphetamine in rats.

    PubMed

    Munzar, P; Kutkat, S W; Miller, C R; Goldberg, S R

    2000-11-17

    The effects of baclofen, an agonist at GABA(B) receptors, were evaluated in rats trained to discriminate 10.0 mg/kg of cocaine or 1. 0 mg/kg of methamphetamine from saline under a fixed-ratio 10 schedule of food delivery. Baclofen (0.56-5.6 mg/kg) did not attenuate the discriminative-stimulus effects of the training dose of cocaine or methamphetamine and did not produce any shift in the cocaine and methamphetamine dose-response curves. Higher baclofen doses (3.0-5.6 mg/kg), however, markedly depressed or completely eliminated food-maintained responding. This suggests that previous reports of baclofen-induced decreases in cocaine self-administration behavior are connected, in some way, with either a general suppression of appetitive behaviors or with sedation and locomotor depression, rather than with any pharmacologically specific effect, and not accompanied by changes in subjective response to cocaine, as assessed by discriminative-stimulus measures.

  14. 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.

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

    PubMed

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

    2016-05-01

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

  16. Attention-Deficit/Hyperactivity Disorder Among Chronic Methamphetamine Users: Frequency, Persistence, and Adverse Effects on Everyday Functioning

    PubMed Central

    Obermeit, Lisa C.; Cattie, Jordan E.; Bolden, Khalima A.; Marquine, Maria J.; Morgan, Erin E.; Franklin, Donald R.; Atkinson, J. Hampton; Grant, Igor; Woods, Steven Paul

    2013-01-01

    Aims Attention-Deficit/Hyperactivity Disorder (ADHD) is widely regarded as a common comorbidity of methamphetamine (MA) dependence, but the frequency, persistence, and real-world impact of ADHD among MA users is not known. Methods Four hundred individuals with MA use disorders within 18 months of evaluation and 355 non-MA using comparison subjects completed a comprehensive neuropsychiatric research battery, including self-report measures of everyday functioning. Results In logistic regression models adjusting for potential confounds, lifetime diagnoses of ADHD as determined by a structured clinical interview were significantly more prevalent among the MA participants (21%) versus comparison subjects (6%), particularly the hyperactive and combined subtypes. MA use was also associated with an increased persistence of combined subtype of ADHD into adulthood. Among the MA users, lifetime ADHD diagnoses were uniquely associated with greater concurrent risk of declines in instrumental activities of daily living, elevated cognitive symptoms in day-to-day life, and unemployment. Conclusions Findings indicate that ADHD is prevalent among chronic MA users, who are at increased risk for persistence of childhood diagnoses of ADHD into their adult years. ADHD also appears to play an important role in MA-associated disability, indicating that targeted ADHD screening and treatment may help to improve real-world outcomes for individuals with MA use disorders. PMID:24018233

  17. Metabolic consequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects.

    PubMed

    Henry, R R; Wiest-Kent, T A; Scheaffer, L; Kolterman, O G; Olefsky, J M

    1986-02-01

    To determine the effects of very-low-calorie diets on the metabolic abnormalities of diabetes and obesity, we have studied 10 obese, non-insulin-dependent diabetic (NIDDM) and 5 obese, nondiabetic subjects for 36 days on a metabolic ward during consumption of a liquid diet of 300 kcal/day with 30 g of protein. Rapid improvement occurred in the glycemic indices of the diabetic subjects, with mean (+/- SEM) fasting plasma glucose falling from 291 +/- 21 to 95 +/- 6 mg/dl (P less than 0.001) and total glycosylated hemoglobin from 13.1 +/- 0.7% to 8.8 +/- 0.3% (P less than 0.001) (normal reference range 5.5-8.5%). Lipid elevations were normalized with plasma triglycerides reduced to less than 100 mg/dl and total plasma cholesterol to less than 150 mg/dl in both groups. Hormonal and substrate responses were also comparable between groups with reductions in insulin and triiodothyronine and moderate elevations in blood and urinary ketoacid levels without a corresponding rise in free fatty acids. Electrolyte balance for sodium, potassium, calcium, and phosphorus was initially negative but approached equilibrium by completion of the study. Magnesium, in contrast, remained in positive balance in both groups throughout. Total nitrogen loss varied widely among all subjects, ranging from 70 to 367 g, and showed a strong positive correlation with initial lean body mass (N = 0.83, P less than 0.001) and total weight loss (N = 0.87, P less than 0.001). The nondiabetic group, which had a significantly greater initial body weight and lean body mass than the diabetic group, also had a significantly greater weight loss of 450 +/- 31 g/day compared with 308 +/- 19 g/day (P less than 0.01) in the diabetic subjects. The composition of the weight lost at completion was similar in both groups and ranged from 21.6% to 31.3% water, 3.9% to 7.8% protein, and 60.9% to 74.5% fat. The contribution of both water and protein progressively decreased and fat increased, resulting in unchanged caloric

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

    PubMed Central

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

    2012-01-01

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

  19. Nesprin-2G, a Component of the Nuclear LINC Complex, Is Subject to Myosin-Dependent Tension

    PubMed Central

    Arsenovic, Paul T.; Ramachandran, Iswarya; Bathula, Kranthidhar; Zhu, Ruijun; Narang, Jiten D.; Noll, Natalie A.; Lemmon, Christopher A.; Gundersen, Gregg G.; Conway, Daniel E.

    2016-01-01

    The nucleus of a cell has long been considered to be subject to mechanical force. Despite the observation that mechanical forces affect nuclear geometry and movement, how forces are applied onto the nucleus is not well understood. The nuclear LINC (linker of nucleoskeleton and cytoskeleton) complex has been hypothesized to be the critical structure that mediates the transfer of mechanical forces from the cytoskeleton onto the nucleus. Previously used techniques for studying nuclear forces have been unable to resolve forces across individual proteins, making it difficult to clearly establish if the LINC complex experiences mechanical load. To directly measure forces across the LINC complex, we generated a fluorescence resonance energy transfer-based tension biosensor for nesprin-2G, a key structural protein in the LINC complex, which physically links this complex to the actin cytoskeleton. Using this sensor we show that nesprin-2G is subject to mechanical tension in adherent fibroblasts, with highest levels of force on the apical and equatorial planes of the nucleus. We also show that the forces across nesprin-2G are dependent on actomyosin contractility and cell elongation. Additionally, nesprin-2G tension is reduced in fibroblasts from Hutchinson-Gilford progeria syndrome patients. This report provides the first, to our knowledge, direct evidence that nesprin-2G, and by extension the LINC complex, is subject to mechanical force. We also present evidence that nesprin-2G localization to the nuclear membrane is altered under high-force conditions. Because forces across the LINC complex are altered by a variety of different conditions, mechanical forces across the LINC complex, as well as the nucleus in general, may represent an important mechanism for mediating mechanotransduction. PMID:26745407

  20. 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.

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

    PubMed Central

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

    2015-01-01

    Background Since 2000, there has been a dramatic increase in methamphetamine use in South Africa, but little is known about the experiences of out-of-treatment users. This mixed-methods study describes the substance use histories, addiction symptoms, and treatment experiences of a community-recruited sample of methamphetamine users in Cape Town. Methods Using respondent driven sampling, 360 methamphetamine users (44% female) completed structured clinical interviews to assess substance abuse and treatment history and computerized surveys to assess drug-related risks. A sub-sample of 30 participants completed in-depth interviews to qualitatively explore experiences with methamphetamine use and drug treatment. Results Participants had used methamphetamine for an average of 7.06 years (SD=3.64). They reported using methamphetamine on an average of 23.49 of the past 30 days (SD=8.90); 60% used daily. The majority (90%) met ICD-10 criteria for dependence, and many reported severe social, financial, and legal consequences. While only 10% had ever received drug treatment, 90% reported that they wanted treatment. In the qualitative interviews, participants reported multiple barriers to treatment, including beliefs that treatment is ineffective and relapse is inevitable in their social context. They also identified important motivators, including desires to be drug free and improve family functioning. Conclusion This study yields valuable information to more effectively respond to emerging methamphetamine epidemics in South Africa and other low- and middle-income countries. Interventions to increase uptake of evidence-based services must actively seek out drug users and build motivation for treatment, and offer continuing care services to prevent relapse. Community education campaigns are also needed. PMID:25977205

  2. Gamma-vinyl GABA inhibits methamphetamine, heroin, or ethanol-induced increases in nucleus accumbens dopamine.

    PubMed

    Gerasimov, M R; Ashby, C R; Gardner, E L; Mills, M J; Brodie, J D; Dewey, S L

    1999-10-01

    We examined the acute effect of the irreversible GABA-transaminase inhibitor, gamma-vinyl GABA (GVG, Sabril((R)), Vigabatrin((R))) on increases in nucleus accumbens (NAc) dopamine (DA) following acute administration of methamphetamine, heroin, or ethanol. Methamphetamine (2.5 mg/kg) produced a dose-dependent increase (2, 700%) in NAc DA. GVG preadministration (300 or 600 mg/kg), however, inhibited this response by approximately 39 and 61%, respectively. The lower dose of methamphetamine (1.25 mg/kg), increased DA by 1, 700%. This response was inhibited to a similar extent (44%) regardless of the GVG dose preadministered (300 or 600 mg/kg). In addition, heroin-induced increases in NAc DA (0.5 mg/kg, 170%) were inhibited or completely abolished by GVG (150 or 300 mg/kg, 65 and 100%, respectively). Finally, at half the dose necessary for heroin, GVG (150 mg/kg) also completely abolished ethanol-induced increases in NAc DA following a 0.25 g/kg challenge dose (140%). Taken with our previous findings using nicotine or cocaine as the challenge drug, these results indicate that GVG attenuates increases in NAc DA by a mechanism common to many drugs of abuse. However, it appears unlikely that an acute dose of GVG can completely inhibit increases in NAc DA following challenges with a drug whose mechanism of action is mediated primarily through the DA reuptake site.

  3. 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.

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

    PubMed

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

    2016-05-01

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

  5. Effect of time-dependent material properties on the mechanical behavior of PFSA membranes subjected to humidity cycling

    NASA Astrophysics Data System (ADS)

    Khattra, Narinder S.; Karlsson, Anette M.; Santare, Michael H.; Walsh, Peter; Busby, F. Colin

    2012-09-01

    A viscoelastic-plastic constitutive model is developed to characterize the time-dependent mechanical response of perfluorosulphonic acid (PFSA) membranes. This model is then used in finite element simulations of a representative fuel cell unit, (consisting of electrodes, gas diffusion layer and bipolar plates) subjected to standardized relative humidity (RH) cycling test conditions. The effects of hold times at constant RH, the feed rate of humidified air and sorption rate of water into the membrane on the stress response are investigated. While the longer hold times at high and low humidity lead to considerable redistribution of the stresses, the lower feed and sorption rates were found to reduce the overall stress levels in the membrane. The redistribution and reduction in stress magnitudes along with inelastic deformation during hydration eventually lead to development of residual tensile stresses after dehydration. Simulations indicate that these tensile stresses can be on the order of 9-10 MPa which may lead to mechanical degradation of the membrane. The simulation results show that time-dependent properties can have a significant effect on the in-plane stress response of the membrane.

  6. d-Cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence

    PubMed Central

    Santa Ana, Elizabeth J.; Prisciandaro, James J.; Saladin, Michael E.; McRae-Clark, Aimee L.; Shaftman, Stephanie R.; Nietert, Paul J.; Brady, Kathleen T.

    2014-01-01

    Background Based on preclinical studies showing that the partial N-methyl-d-aspartate (NMDA) agonist d-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. Methods In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. Results DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. PMID:25808169

  7. The disruptive effects of methamphetamine on delayed-matching-to-sample performance reflect proactive interference and are reduced by SCH23390.

    PubMed

    Macaskill, Anne C; Harrow, Catherine C; Harper, David N

    2015-01-01

    Different drugs produce different patterns of impairment on delayed matching-to-sample tasks. For example, (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces an increase in proactive interference. That is, subjects are less accurate when they are required to make a response different to the one they made on the immediately previous trial. The current study assessed whether methamphetamine also produces this particular pattern of disruption in delayed matching-to-sample performance in rats. Methamphetamine primarily reduced accuracy on trials where the correct response differed from the one made on the previous trial. Thus methamphetamine, like MDMA and other stimulant-based drugs of abuse, increased proactive interference. This impairment was reduced by prior administration of the dopamine D1 antagonist SCH23390. These results further extend a general conclusion that a range of stimulant-based drugs may disrupt working memory function indirectly via a tendency to repeat previously made responses and that this disruption is related to D1 receptor activity.

  8. 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

  9. 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.

  10. 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

  11. Study on the THz spectrum of methamphetamine

    NASA Astrophysics Data System (ADS)

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

    2005-09-01

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

  12. Determination of methamphetamine enantiomer composition in human hair by non-chiral liquid chromatography-tandem mass spectrometry method.

    PubMed

    Shu, Irene; Alexander, Amy; Jones, Mary; Jones, Joseph; Negrusz, Adam

    2016-08-15

    Chiral separation is crucial for investigating methamphetamine positive cases. While (S)-(+)-enantiomer of methamphetamine (S-MAMP) is a schedule II controlled substance, (R)-(-)-enantiomer (R-MAMP) is an active ingredient of a few over-the-counter drugs in the United States. Among biological specimen types, hair provides greater detection window than blood, urine or oral fluid, and are therefore regarded with particular interest. Herein we describe a novel non-chiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to directly determine methamphetamine enantiomeric composition (percentage) in hair specimens. Hair samples were washed once with acetone, powdered, incubated overnight at 53°C in 0.1M hydrochloric acid (HCl), and subjected to a solid phase extraction (SPE). The extracts were derivatized using Marfey's reagent at 53°C for 60min. The final mixture was analyzed by LC-MS/MS. Chromatographic separation was achieved using a C18 Kinetex analytical column and 60% (v/v) aqueous methanol as mobile phase (isocratic). Triple quadrupole mass spectrometer was equipped with an electro-spray ionization (ESI) source operating in negative mode and the chromatograms were acquired using a multiple-reaction monitoring (MRM) approach. The results were expressed as ratio of R- to S-MAMP and then derived to composition percentages without requiring quantitating each enantiomer. The method was precise and accurate across 0-100% S-composition at a range of 80-18,000pg/mg. The performance of the new method was compared with an (S)-(-)-N-trifluoroacetylprolyl chloride (S-TPC) derivatization and gas chromatography-mass spectrometry (GC-MS) method on authentic methamphetamine-positive hair samples. Not only the new Marfey's reagent approach presented satisfactory correlation with the S-TPC approach, but it also exhibited significantly improved quality (e.g., S/N) of the chromatograms. In summary, our protocol employs cost effective and minimally hazardous Marfey

  13. Association of low birth weight with beta cell function in the adult first degree relatives of non-insulin dependent diabetic subjects.

    PubMed Central

    Cook, J T; Levy, J C; Page, R C; Shaw, J A; Hattersley, A T; Turner, R C

    1993-01-01

    OBJECTIVE--To examine the relation between birth weight and beta cell function in the first degree relatives of non-insulin dependent diabetic subjects. DESIGN--Cross sectional study of 101 adults of known birth weight from 47 families which had at least one member with non-insulin dependent diabetes. SUBJECTS--101 white adults aged mean 43 (SD 7) years. SETTING--Oxfordshire, England. MAIN OUTCOME MEASURES--Glucose tolerance was measured by continuous infusion glucose tolerance test. beta cell function and insulin sensitivity were calculated from the fasting plasma glucose and insulin concentrations with homeostasis model assessment. beta cell function was standardised to allow for the confounding effects of age and obesity. RESULTS--Twenty seven subjects had non-insulin dependent diabetes, 32 had impaired glucose tolerance, and 42 were normoglycaemic. Birth weight correlated with the beta cell function of the complete cohort (rs = 0.29, p = 0.005), the non-insulin dependent diabetic subjects (rs = 0.50, p = 0.023), and the non-diabetic subjects (rs = 0.29, p = 0.013). The non-insulin dependent diabetic (n = 27) and the non-diabetic (n = 74) subjects had similar mean (inter-quartile range) centile birth weight 50% (19%-91%), and 53% (30%-75%) respectively. Non-insulin dependent diabetic subjects had significantly lower beta function than the non-diabetic subjects: 69% (48%-83%) v 97% (86%-120%), p < 0.001. CONCLUSIONS--The cause of the association between low birth weight and reduced beta cell function in adult life is uncertain. Impaired beta cell function in non-insulin dependent diabetic subjects was not accounted for by low birth weight, and genetic or environmental factors are likely to be necessary for development of diabetes. PMID:8461648

  14. Env-Specific IgA from Viremic HIV-Infected Subjects Compromises Antibody-Dependent Cellular Cytotoxicity

    PubMed Central

    Ruiz, María Julia; Ghiglione, Yanina; Falivene, Juliana; Laufer, Natalia; Holgado, María Pía; Socías, María Eugenia; Cahn, Pedro; Sued, Omar; Giavedoni, Luis; Salomón, Horacio; Gherardi, María Magdalena; Rodríguez, Ana María

    2015-01-01

    ABSTRACT Elucidating the factors that modulate HIV-specific antibody-dependent cellular cytotoxicity (ADCC) will help in understanding its role in HIV immunity. The aim of this study was to determine whether IgA could modify the magnitude of ADCC in HIV infection, abrogating its protective role. Plasma samples from 20 HIV-positive (HIV+) subjects enrolled during primary HIV infection (PHI), 10 chronically infected subjects (chronic), and 7 elite controllers (EC) were used. ADCC was determined by using a fluorometric ADCC assay, before and after removal of plasma IgA. Data were analyzed by using nonparametric statistics. ADCC was documented in 80% of PHI enrollment samples and in 100% of PHI 12-month, chronic, and EC samples; it peaked after acute infection, reached a plateau in chronic infection, and decreased after initiation of antiretroviral treatment (ART). Significant associations between ADCC and disease progression were found only after removal of plasma IgA from 12-month PHI samples: the magnitude of ADCC not only increased after IgA removal but also correlated with CD4+ T-cell preservation. This work provides evidence that gp120-specific IgA was capable of modifying ADCC responses during natural HIV infection for the first time and adds to similar evidence provided in other settings. Furthermore, it underscores the complexity of the ADCC phenomenon and will help in an understanding of its underlying mechanisms. IMPORTANCE Although the induction of ADCC-mediating antibodies in HIV-infected subjects has been extensively documented, the association of these antibodies with protection from disease progression is poorly understood. Here, we demonstrate that plasma IgA is a factor capable of modifying the magnitude of IgG-mediated ADCC in HIV infection, mitigating its beneficial effect. These results help in understanding why previous studies failed to demonstrate correlations between ADCC and disease progression, and they also contribute to the notion that an

  15. Everyday problems with executive dysfunction and impulsivity in adults recovering from methamphetamine addiction

    PubMed Central

    Ellis, Carilyn; Hoffman, William; Jaehnert, Sarah; Plagge, Jane; Loftis, Jennifer M.; Schwartz, Daniel; Huckans, Marilyn

    2014-01-01

    Objectives Compared with non-addicted controls (CTLs), adults in remission from methamphetamine addiction (MA-REM) evidence impairments on objective measures of executive functioning and impulsivity. Methods To evaluate the impact of these impairments in MA-REM adults, demographically matched groups (MA-REM, n=30; CTLs, n=24) completed objective and self-report measures of executive functioning and impulsivity. Results MA-REM adults demonstrated significantly (p < 0.050) greater objective and subjective problems with executive functioning and impulsivity. Conclusions These results suggest that adults in MA-REM are aware of their deficits and that these deficits have significant impact in everyday life. PMID:27034621

  16. 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

  17. Measurement of androgen and estrogen receptors in breast tissue from subjects with anabolic steroid-dependent gynecomastia.

    PubMed

    Calzada, L; Torres-Calleja, J; Martinez, J M; Pedrón, N

    2001-08-17

    In order to assess the relationship between anabolic steroid administration and gynecomastia, we studied the effects produced by administering nandrolone decanoate and a mixture of propionate, phenilpropionate, isocaproate and testosterone decanoate to bodybuilders during a six month period. The following significant changes occurred: a 53% reduction in serum testosterone; LH and FSH levels were suppressed to 77% and 87%, respectively, in comparison to control values; and although 45% of the subjects showed an increase in serum estradiol levels, no statistically significant differences were found compared with control estradiol levels. With regard to estradiol and androgen receptors, 85% of gynecomastia tissue contained estradiol or androgen receptors, while 40% contained both. The mean values of estradiol and androgen receptors in the cytosol were 65 +/- 10 and 52 +/- 5 fmol/mg protein, respectively. Nuclear androgen and estradiol receptor levels were 33 +/- 7 and 67.5 +/- 9 fmol/mg protein, respectively. The presence of hormone receptors in gynecomastia receptive cells provides support for the hypothesis that gynecomastia is steroid-dependent.

  18. Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

    PubMed Central

    Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

    2015-01-01

    Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

  19. Methamphetamine-induced spectrin proteolysis in the rat striatum.

    PubMed

    Staszewski, Robert D; Yamamoto, Bryan K

    2006-03-01

    Methamphetamine (METH) is a widely abused psychostimulant. Multiple high doses of METH cause long-term toxicity to dopamine (DA) and serotonin (5-HT) nerve terminals in the brain, as evidenced by decreases in DA and 5-HT content, decreases in tyrosine and tryptophan hydroxylase activities, decreases in DA and 5-HT re-uptake sites, and nerve terminal degeneration. Multiple high doses of METH are known to elicit a rapid increase in DA release and hyperthermia. Although METH also produces a delayed and sustained rise in glutamate, no studies have shown whether METH produces structural evidence of excitotoxicity in striatum, or identified the receptors that mediate this toxicity directly, independent of alterations in METH-induced hyperthermia. These experiments investigated whether METH can cause excitotoxicity as evidenced by cytoskeletal protein breakdown in a glutamate receptor-dependent manner. METH increased calpain-mediated spectrin proteolysis in the rat striatum 5 and 7 days after METH administration without affecting caspase 3-dependent spectrin breakdown. This effect was completely blocked with the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, GYKI 52466, but not the NMDA receptor antagonist, MK-801. However, AMPA or NMDA receptor antagonism did not attenuate the METH-induced depletions of the dopamine transporter (DAT). Independent mechanisms involved in mediating spectrin proteolysis and DAT protein loss are discussed.

  20. Methamphetamine blood concentrations in human abusers: application to pharmacokinetic modeling.

    PubMed

    Melega, William P; Cho, Arthur K; Harvey, Dennis; Laćan, Goran

    2007-04-01

    Characterization of methamphetamine's (METH) dose-dependent effects on brain neurochemistry may represent a critical component for better understanding the range of resultant behavioral pathologies. Most human studies, however, have assessed only the effects of long term, high dose METH abuse (e.g., greater than 1000 mg/day) in individuals meeting DSM-IV criteria for METH dependence. Yet, for the majority of METH abusers, their patterns of METH exposure that consist of lower doses remain less well-characterized. In this study, blood samples were obtained from 105 individuals detained by police for possible criminal activity and testing positive for stimulants by EMIT assay. METH blood concentrations were subsequently quantified by GC-MS and were predominantly in the low micromolar range (0.1-11.1 microM), with median and mean values of 1.3 microM (0.19 mg/l) and 2 microM (0.3 mg/l), respectively. Pharmacokinetic calculations based on these measured values were used to estimate initial METH body burdens, the median value being 52 mg. Modeling a 52 mg dose for a 4 day-METH maintenance exposure pattern of 4 doses/day at 4 h intervals showed that blood concentrations remained between 1 and 4 microM during this period. Collectively, these data present evidence for a METH exposure pattern distinct from high dose-METH abuse and provide the rationale for assessing potential brain pathology associated with such lower dose-METH exposure.

  1. Methamphetamine abuse and oral health: a pilot study of "meth mouth".

    PubMed

    Ravenel, Michele C; Salinas, Carlos F; Marlow, Nicole M; Slate, Elizabeth H; Evans, Zachary P; Miller, Peter M

    2012-03-01

    Abuse of methamphetamine (meth), a potent central nervous system stimulant, has been associated with significant dental disease. Current descriptions of "meth mouth" are limited in their scope and fail to illuminate the potential pathogenic mechanisms of meth for oral disease. The purpose of this pilot study was to characterize the oral health of subjects with a history of meth abuse as compared to nonabusing control subjects. A total of 28 meth abusers and 16 control subjects were enrolled. Interviews and surveys regarding meth abuse, dental history, oral hygiene, and diet were collected. A comprehensive oral cavity examination including salivary characterization was completed. We observed significantly higher rates of decayed surfaces, missing teeth, tooth wear, plaque, and calculus among meth abusers. No significant difference in salivary flow rates were noted, yet results showed significant trends for lower pH and decreased buffering capacity. These findings suggest that salivary quality may play a more important role in meth mouth than previously considered. Salivary analysis may be useful when managing a dental patient with history of methamphetamine abuse.

  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. Exercise protects against methamphetamine-induced aberrant neurogenesis.

    PubMed

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-09-28

    While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus.

  4. Famprofazone use can be misinterpreted as methamphetamine abuse.

    PubMed

    Chan, Kuei-Hui; Hsu, Mei-Chich; Tseng, Chen-Yu; Chu, Wei-Lan

    2010-01-01

    Famprofazone, a major ingredient of Gewolen, is an analgesic that has been demonstrated to be metabolized to methamphetamine (MA) and amphetamine (AM) following administration. Therefore, a famprofazone user may be interpreted as an illicit MA abuser in Taiwan because the user's urine tested positive for MA. The purpose of this study was to investigate whether the concentration of MA metabolized from a single dose of Gewolen users would offend the official controlled substance regulation and be identified as MA-positive. Subjects (n = 6) received 25 mg of famprofazone and collected all urine specimens at certain timed intervals for 48 h after drug administration. The urine specimens were screened by immunoassay and then confirmed by gas chromatography-mass spectrometry (GC-MS). The highest concentration of amphetamines by immunoassay was 1954 ng/mL, and 18.8% of the urine specimens' amphetamines concentrations exceeded 500 ng/mL. The MA and AM concentrations by GC-MS analysis of these urine specimens ranged from 901 to 2670 ng/mL and 208 to 711 ng/mL, respectively. These urine specimens were interpreted as MA-positive (>or= 500 ng/mL MA and >or= 100 ng/mL AM), according to the official test methods of Taiwan. The MA positive results appeared within 2-34 h. It is therefore clearly possible to misinterpret the legitimate famprofazone user as an MA abuser in Taiwan.

  5. Exercise protects against methamphetamine-induced aberrant neurogenesis

    PubMed Central

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-01-01

    While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus. PMID:27677455

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

    PubMed Central

    Mayo, Leah M.; de Wit, Harriet

    2016-01-01

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

  7. Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects.

    PubMed

    Meyer, Barbara J; Hammervold, Tone; Rustan, Arild Chr; Howe, Peter R C

    2007-03-01

    The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = -0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = -0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.

  8. Impact of methamphetamine on infection and immunity

    PubMed Central

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

    2015-01-01

    The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation. PMID:25628526

  9. Mechanisms of methamphetamine-induced dopaminergic neurotoxicity.

    PubMed

    Riddle, Evan L; Fleckenstein, Annette E; Hanson, Glen R

    2006-01-01

    Methamphetamine (METH) is a powerful stimulant of abuse with potent addictive and neurotoxic properties. More than 2.5 decades ago, METH-induced damage to dopaminergic neurons was described. Since then, numerous advancements have been made in the search for the underlying mechanisms whereby METH causes these persistent dopaminergic deficits. Although our understanding of these mechanisms remains incomplete, combinations of various complex processes have been described around a central theme involving reactive species, such as reactive oxygen and/or nitrogen species (ROS and RNS, respectively). For example, METH-induced hyperthermia, aberrant dopamine(DA), or glutamate transmission; or mitochondrial disruption leads to the generation of reactive species with neurotoxic consequences. This review will describe the current understanding of how high-dose METH administration leads to the production of these toxic reactive species and consequent permanent dopaminergic deficits.

  10. Methamphetamine inhibits antigen processing, presentation, and phagocytosis.

    PubMed

    Tallóczy, Zsolt; Martinez, Jose; Joset, Danielle; Ray, Yonaton; Gácser, Attila; Toussi, Sima; Mizushima, Noboru; Nosanchuk, Joshua D; Nosanchuk, Josh; Goldstein, Harris; Loike, John; Sulzer, David; Santambrogio, Laura

    2008-02-08

    Methamphetamine (Meth) is abused by over 35 million people worldwide. Chronic Meth abuse may be particularly devastating in individuals who engage in unprotected sex with multiple partners because it is associated with a 2-fold higher risk for obtaining HIV and associated secondary infections. We report the first specific evidence that Meth at pharmacological concentrations exerts a direct immunosuppressive effect on dendritic cells and macrophages. As a weak base, Meth collapses the pH gradient across acidic organelles, including lysosomes and associated autophagic organelles. This in turn inhibits receptor-mediated phagocytosis of antibody-coated particles, MHC class II antigen processing by the endosomal-lysosomal pathway, and antigen presentation to splenic T cells by dendritic cells. More importantly Meth facilitates intracellular replication and inhibits intracellular killing of Candida albicans and Cryptococcus neoformans, two major AIDS-related pathogens. Meth exerts previously unreported direct immunosuppressive effects that contribute to increased risk of infection and exacerbate AIDS pathology.

  11. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

  12. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  14. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

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

    ERIC Educational Resources Information Center

    Connell-Carrick, Kelli

    2007-01-01

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

  16. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine...

  17. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    ERIC Educational Resources Information Center

    Lamonica, Aukje K.; Boeri, Miriam

    2012-01-01

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

  19. The Untold Story of Mexico’s Rise and Eventual Monopoly of the Methamphetamine Trade

    DTIC Science & Technology

    2008-06-01

    clandestine methamphetamine production and abuse in the United States.64 64 U.S. Drug Enforcement...reported that: Meth remains the largest drug threat throughout Wyoming, and methamphetamine arrests exceed arrests for all other drugs. Clandestine ...MEXICO’S RISE AND EVENTUAL MONOPOLY OF THE METHAMPHETAMINE TRADE by Steven Scott Whitworth June 2008 Thesis Advisor: Jeanne Giraldo

  20. 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.

  1. Methamphetamine Self-Administration Acutely Decreases Monoaminergic Transporter Function

    PubMed Central

    McFadden, Lisa M.; Stout, Kristen A.; Vieira-Brock, Paula L.; Allen, Scott C.; Nielsen, Shannon M.; Wilkins, Diana G.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Numerous pre-clinical studies have demonstrated that non-contingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of non-contingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence. PMID:22120988

  2. Methamphetamine self-administration acutely decreases monoaminergic transporter function.

    PubMed

    McFadden, Lisa M; Stout, Kristen A; Vieira-Brock, Paula L; Allen, Scott C; Nielsen, Shannon M; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2012-03-01

    Numerous preclinical studies have demonstrated that noncontingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence.

  3. Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage.

    PubMed

    Sanchez, Ana B; Varano, Giuseppe P; de Rozieres, Cyrus M; Maung, Ricky; Catalan, Irene C; Dowling, Cari C; Sejbuk, Natalia E; Hoefer, Melanie M; Kaul, Marcus

    2015-10-19

    HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.

  4. The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access

    PubMed Central

    Orio, Laura; Wee, Sunmee; Newman, Amy H.; Pulvirenti, Luigi; Koob, George F.

    2010-01-01

    Previous work suggests a role for dopamine D3-like receptors in psychostimulant reinforcement. The development of new compounds acting selectively at dopamine D3 receptors has opened new possibilities to explore the role of these receptors in animal models of psychostimulant dependence. Here we investigated whether the dopamine D3 partial agonist CJB090 (1–10 mg/kg, i.v) and the D3 antagonist PG01037 (8–32 mg/kg, s.c.,) modified methamphetamine (0.05 mg/kg/injection) intravenous self-administration under fixed- (FR) and progressive- (PR) ratio schedules in rats allowed limited (short access, ShA; 1h sessions 3 days/week) or extended access (long access, LgA; 6h sessions 6 days/week). Under a FR1 schedule, the highest dose of the D3 partial agonist CJB090 selectively reduced methamphetamine self-administration in LgA but not in ShA rats, whereas the full D3 antagonist PG01037 produced no effect in either group. Under a PR schedule of reinforcement, the D3 partial agonist CJB090 reduced the maximum number of responses performed (“breakpoint”) for methamphetamine in LgA rats at the doses of 5 and 10 mg/kg and also it produced a significant reduction in the ShA group at the highest dose. However, the D3 full antagonist PG01037 only reduced PR methamphetamine self-administration in LgA rats at the highest dose of 32 mg/kg with no effect in the ShA group. The results suggest that rats might be more sensitive to pharmacological modulation of dopamine D3 receptors following extended access to methamphetamine self-administration, opening the possibility that D3 receptors play a role in excessive methamphetamine intake. PMID:20456290

  5. Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage

    PubMed Central

    Sanchez, Ana B.; Varano, Giuseppe P.; de Rozieres, Cyrus M.; Maung, Ricky; Catalan, Irene C.; Dowling, Cari C.; Sejbuk, Natalia E.; Hoefer, Melanie M.

    2015-01-01

    HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine. PMID:26482305

  6. Effect of Aripiprazole, a Partial Dopamine D2 Receptor Agonist, on Increased Rate of Methamphetamine Self-Administration in Rats with Prolonged Session Duration

    PubMed Central

    Wee, Sunmee; Wang, Zhixia; Woolverton, William L; Pulvirenti, Luigi; Koob, George F

    2009-01-01

    Aripiprazole is a dopamine (DA) D2 receptor partial agonist, approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. DA receptor partial agonists have been previously assessed as potential therapeutic agents for cocaine dependence. The present experiment examined the effect of aripiprazole on methamphetamine self-administration in a rodent model of an increasing drug self-administration with prolonged session duration. Wistar rats were allowed to self-administer methamphetamine (0.05 mg/kg/injection, intravenously) in either 1-h (short access: ShA rats) or 6-h sessions (long access: LgA rats). After 15 sessions, the dose–response function of methamphetamine was determined under either a progressive- or a fixed-ratio schedule. Next, the effect of aripiprazole (0.3–10 mg/kg, subcutaneuously (s.c.)) on the dose–response function was examined. LgA rats exhibited an increasing rate of methamphetamine self-administration. Responding for methamphetamine by LgA rats was higher than that of ShA rats under both schedules. Pretreatment with aripiprazole shifted the dose–response function of methamphetamine to the right in both LgA and ShA rats. However, the effect of aripiprazole was greater in LgA than ShA rats. In in vitro receptor binding assay, no change in the level of D2 DA receptors in the nucleus accumbens and the striatum was found in any group. The present data suggest increased sensitivity of the dopaminergic system to aripiprazole in LgA rats compared with ShA rats. However, mechanisms other than downregulation of D2 DA receptors in the nucleus accumbens and the striatum may be responsible for the increased sensitivity of the dopaminergic function in LgA rats. PMID:17327886

  7. The CSAT methamphetamine treatment program: research design accommodations for "real world" application.

    PubMed

    Huber, A; Lord, R H; Gulati, V; Marinelli-Casey, P; Rawson, R; Ling, W

    2000-01-01

    The Methamphetamine Treatment Program (MTP), funded by the Center for Substance Abuse Treatment, has the objectives of implementing the Matrix outpatient model and evaluating that model in comparison to the existing community "treatments as usual." Seven organizations in three western states (California, Montana, and Hawaii) were selected to participate in this randomized, controlled, multisite project in what constitutes the largest trial to date of treatment for methamphetamine (MA) dependence. One hundred fifty MA-dependent patients recruited at each site are randomly assigned to receive either the Matrix model, a manualized program of intensive outpatient treatment, or the site's standard treatment, "treatment as usual." Participants are evaluated at admission, weekly during treatment, at the time of scheduled discharge, and at six and 12 months after admission. Dependent measures assess changes in drug use, HIV risk behaviors, quality of life, and patient satisfaction. Cost analyses to quantify treatment costs and determine the association between costs and clinical outcomes will be conducted. A number of adjustments in the original study design have been necessitated by the realities of community sites' strengths and limitations. Experiences from this multisite project will also provide a model for other efforts to transfer research-based treatments into community settings. This article describes the main aims of the project, the background and rationale for the study design, a brief description of the research plan, and methods implemented to protect the integrity of the science.

  8. Impaired memory and reduced sensitivity to the circadian period lengthening effects of methamphetamine in mice selected for high methamphetamine consumption.

    PubMed

    Olsen, Reid H J; Allen, Charles N; Derkach, Victor A; Phillips, Tamara J; Belknap, John K; Raber, Jacob

    2013-11-01

    Drug abuse runs in families suggesting the involvement of genetic risk factors. Differences in addiction-related neurobiological systems, including learning and memory and circadian rhythms, may exist prior to developing addiction. We characterized the cognitive phenotypes and the free-running circadian period of mouse lines selectively bred for high methamphetamine (MA) drinking (MA high drinking or MAHDR) and low MA drinking (MA low drinking or MALDR). MA-naïve MALDR mice showed spatial memory retention while MAHDR mice did not. MA-naïve MAHDR mice had elevated hippocampal levels of the AMPA receptor subunits GluA2 (old terminology: GluR2), but not GluA1 (old terminology: GluR1). There were no line differences in the free running period (τ) when only water was available. During a 25 mg/L MA solution access period (vs water), there was an increase in τ in MALDR but not MAHDR mice, although MAHDR mice consumed significantly more MA. During a 50 mg/L MA solution access period (vs water), both lines showed an increased τ. There was a positive correlation between MA consumption and τ from baseline in MALDR, but not MAHDR, mice. Thus, a heritable proclivity for elevated MA self-administration may be associated with impairments in hippocampus-dependent memory and reduced sensitivity to effects of MA on lengthening of the circadian period.

  9. Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term.

    PubMed

    Smith, Lynne; Yonekura, M Lynn; Wallace, Toni; Berman, Nancy; Kuo, Jennifer; Berkowitz, Carol

    2003-02-01

    To determine fetal growth and the incidence of withdrawal symptoms in term infants exposed to methamphetamine in utero, we retrospectively identified neonates whose mothers used methamphetamine during pregnancy and matched them to unexposed newborns. Exclusion criteria included multiple and preterm gestations. Although there were no differences in infant growth parameters between the methamphetamine-exposed and methamphetamine-unexposed neonates, methamphetamine exposure throughout gestation was associated with decreased growth relative to infants exposed only for the first two trimesters. In addition, there were significantly more small for gestational age infants in the methamphetamine group compared with the unexposed group. Methamphetamine-exposed infants whose mothers smoked had significantly decreased growth relative to infants exposed to methamphetamine alone. Withdrawal symptoms (as determined by a previously reported scoring system) requiring pharmacologic intervention were observed in 4% of methamphetamine-exposed infants. These preliminary findings indicate that methamphetamine use is associated with growth restriction in infants born at term.

  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. Comparing injection and non-injection routes of administration for heroin, methamphetamine, and cocaine users in the United States.

    PubMed

    Novak, Scott P; Kral, Alex H

    2011-01-01

    Research examining the demographic and substance use characteristics of illicit drug use in the United States has typically failed to consider differences in routes of administration or has exclusively focused on a single route of administration?injection drug use. Data from National Survey on Drug Use and Health were used to compare past-year injection drug users and non-injection drug users' routes of administration of those who use the three drugs most commonly injected in the United States: heroin, methamphetamine, and cocaine. Injection drug users were more likely than those using drugs via other routes to be older (aged 35 and older), unemployed, possess less than a high school education, and reside in rural areas. IDUs also exhibited higher rates of abuse/dependence, perceived need for substance abuse treatment, and co-occurring physical and psychological problems. Fewer differences between IDUs and non-IDUs were observed for heroin users compared with methamphetamine or cocaine users.

  12. Methamphetamine Consumption during Pregnancy - Effects on Child Health.

    PubMed

    Dinger, Jürgen; Hinner, Patricia; Reichert, Jörg; Rüdiger, Mario

    2017-02-08

    Methamphetamine abuse during pregnancy represents an emerging health care problem. The consequences are not only of relevance to the pregnant women, but also their unborn child. It is associated with an increased risk of preeclampsia and hypertension, fetal demise, preterm delivery, and intrauterine growth restriction. The deleterious effects of prenatal methamphetamine exposure on the developing fetal brain may lead to long-term neuro-developmental and behavioral problems.Given the current evidence, abuse of methamphetamine during pregnancy must be of utmost concern to health care professionals and to policy-makers. As it has been described for neonatal abstinence syndrome, a multi-professional team is required to improve care of affected women and families. A multi-disciplinary approach is needed, including good prenatal care of pregnant women, perinatal care by specialized obstetricians and neonatologists, and psychiatric treatment by an addiction specialist. Furthermore, families should be integrated into appropriate social support networks.For the development of a structured support program for pregnant women with methamphetamine consumption, methamphetamine use disorder should be considered as a disease that requires medical treatment as well as psychological and social support. The pregnancy should be considered as a window of opportunity to provide the required help.

  13. Methamphetamine abuse and “meth mouth” in Europe

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

    Turowski, Patric; Kenny, Bridget-Ann

    2015-01-01

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

  16. Methamphetamine use among rural White and Native American adolescents: an application of the stress process model.

    PubMed

    Eitle, David J; Eitle, Tamela McNulty

    2013-01-01

    Methamphetamine use has been identified as having significant adverse health consequences, yet we know little about the correlates of its use. Additionally, research has found that Native Americans are at the highest risk for methamphetamine use. Our exploratory study, informed by the stress process model, examines stress and stress buffering factors associated with methamphetamine use among a cross-sectional sample of rural White and Native American adolescents (n = 573). Results of logistic regression analyses revealed mixed support for the stress process model; while stress exposure and family methamphetamine use predicted past year methamphetamine use, the inclusion of these variables failed to attenuate the association between race and past year use.

  17. Methamphetamine abuse and dentistry: a review of the literature and presentation of a clinical case.

    PubMed

    Goodchild, Jason H; Donaldson, Mark

    2007-01-01

    Methamphetamine is not a new drug. It has a long and storied history of legitimate clinical use and recreational abuse. Unfortunately, abuse of methamphetamine is increasing with alarming frequency in the United States and leads to appalling destruction of dentition. The pathognomonic effects of methamphetamine abuse on teeth have led to the term "meth mouth." This term, while descriptive of the clinical appearance of patients, is a misnomer. A review of available information on methamphetamine abuse is presented and discussed. A clinical case is documented to help clinicians recognize and manage patients who may be abusing methamphetamines.

  18. Vascular and extravascular immunoreactivity for Intercellular Adhesion Molecule 1 in the orbitofrontal cortex of subjects with major depression: age-dependent changes

    PubMed Central

    Miguel-Hidalgo, Jose Javier; Overholser, James C.; Jurjus, George J.; Meltzer, Herbert Y.; Dieter, Lesa; Konick, Lisa; Stockmeier, Craig A.; Rajkowska, Grazyna

    2011-01-01

    Background Vascular and immune alterations in the prefrontal cortex may contribute to major depression in elderly subjects. Intercellular adhesion molecule-1 (ICAM-1), major inflammatory mediator in vessels and astrocytes, could be altered in geriatric depression, but little is known about its age-dependent expression in subjects with depression and its relationship to astrocytes identified by the marker glial fibrillary acidic protein (GFAP), found to be reduced in depression. Methods We measured the percentage of gray matter area fraction covered by ICAM-1 immunoreactivity in blood vessels and in extravascular accumulations of ICAM-1 immunoreactivity in 19 non-psychiatric comparison subjects and 18 subjects with major depression, all characterized by postmortem psychological diagnosis. Association of extravascular ICAM-1 to GFAP-positive astrocytes was investigated by double-labeling immunofluorescence. Results Vascular and extravascular fractions of ICAM-1 immunoreactivity were lower in subjects with MDD than in non-psychiatric comparison subjects. Non-psychiatric comparison subjects older than 60 experienced dramatic increase in extravascular ICAM-1 immunoreactivity, but this increase was attenuated in elderly subjects with MDD, particularly in those dying by suicide. Most extracellular ICAM-1 immunoreactivity was coextensive with GFAP-immunoreactive astrocytes in both groups. Limitations Heterogeneity in type and dosage of antidepressant medication. Difficulty in determining the exact onset of depression in subjects older than 60 at the time of death. Routine cerebrovascular pathological screening may miss subtle subcellular and molecular changes. Conclusions There is significant attenuation of extravascular and vascular ICAM-1 immunoreactivity in elderly subjects with major depression suggesting an astrocyte-associated alteration in immune function in the aging orbitofrontal cortex of subjects with MDD. PMID:21536333

  19. Sustained-Release Methylphenidate in a Randomized Trial of Treatment of Methamphetamine Use Disorder

    PubMed Central

    Ling, Walter; Chang, Linda; Hillhouse, Maureen; Ang, Alfonso; Striebel, Joan; Jenkins, Jessica; Hernandez, Jasmin; Olaer, Mary; Mooney, Larissa; Reed, Susan; Fukaya, Erin; Kogachi, Shannon; Alicata, Daniel; Holmes, Nataliya; Esagoff, Asher

    2014-01-01

    Background and aims No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioural support and motivational incentives. Design This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT), and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. Setting Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. Participants 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20). Measurements The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events, and treatment satisfaction. Findings No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (p=0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (p=0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events, and treatment satisfaction. Conclusions Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioural support for moderate to severe methamphetamine use disorder but this requires confirmation. PMID:24825486

  20. Agmatine: identification and inhibition of methamphetamine, kappa opioid, and cannabinoid withdrawal in planarians.

    PubMed

    Rawls, Scott M; Gerber, Kristin; Ding, Zhe; Roth, Christopher; Raffa, Robert B

    2008-12-01

    Agmatine blocks morphine physical dependence in mammals, but its effects on withdrawal signs caused by other abused drugs have been less studied. One of the reasons is that withdrawal to some of these drugs is difficult to quantify in mammals. An alternative to mammals is planarians, a type of flatworm. Planarians possess mammalian-like neurotransmitters and display withdrawal from amphetamines, benzodiazepines, cannabinoids, cocaine, and opioids. The withdrawal is manifested as a reduction in locomotor behavior following discontinuation of drug exposure. In the present study, our goal was to identify agmatine in planarians and to determine if planarians exposed to agmatine display withdrawal to methamphetamine, a cannabinoid receptor agonist (WIN 55,212-2), or a kappa-opioid receptor agonist (U-50,488H). Neurochemical experiments revealed that the concentration of agmatine in planarians was 185 +/- 33.7 pmol per mg of planarian weight (dry weight). In behavioral experiments, withdrawal (i.e., reduced locomotor activity) was observed when planarians exposed to each drug (10 microM) for 60 min were placed into water. The withdrawal was attenuated when methamphetamine- or U-50,488H-exposed planarians were tested in agmatine (100 microM). Withdrawal was inhibited similarly when planarians coexposed to agmatine (100 microM) plus methamphetamine (10 microM), WIN 55,212-2 (10 microM), or U-50,488H (10 microM) were tested in water. Arginine, the metabolic precursor to agmatine, was ineffective. Our results identify endogenous agmatine in planarians and demonstrate that agmatine exposure blocks withdrawal to three different drugs in planarians. This suggests that a change in agmatine signaling is a common mechanism in the withdrawal caused by these drugs, at least in planarians.

  1. Methamphetamine use in Central Germany: protocol for a qualitative study exploring requirements and challenges in healthcare from the professionals' perspective

    PubMed Central

    Hoffmann, Laura; Schumann, Nadine; Fankhaenel, Thomas; Thiel, Carolin; Klement, Andreas; Richter, Matthias

    2016-01-01

    Introduction The synthetic drug methamphetamine with its high addiction potential is associated with substantial adverse health effects. In Germany, especially Central Germany, the increase in the consumption of methamphetamine has exceeded that of other illegal drugs. The treatment system and service providers are facing new challenges due to this rise in consumption. This qualitative study will explore the demand created by the increasing healthcare needs of methamphetamine-addicted persons in Central Germany, and the difficulty of rehabilitating addicted people. Methods and analysis The collection of empirical data will take place in a consecutive, two-stage process. In the first part of data collection, the experiences and perspectives of 40 professionals from numerous healthcare sectors for methamphetamine-addicted persons will be explored with the help of semistructured face-to-face interviews and probed by the research team. These findings will be discussed in 2 focus groups consisting of the participants of the face-to-face interviews; these group discussions comprise the second part of the data collection process. The interviews will be audio recorded, transcribed, and then subjected to qualitative content analysis. Ethics and dissemination All interviewees will receive comprehensive written information about the study, and sign a declaration of consent prior to the interview. The study will comply rigorously with data protection legislation. The research team has obtained the approval of the Ethical Review Committee at the Martin Luther University Halle-Wittenberg, Germany. The results of the study will be published in high-quality, peer-reviewed international journals, presented at several congresses and used to design follow-up research projects. Trial registration number VfD_METH_MD_15_003600. PMID:27256092

  2. 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.

  3. Differential behavioral responses of the spontaneously hypertensive rat to methylphenidate and methamphetamine: lack of a rewarding effect of repeated methylphenidate treatment.

    PubMed

    dela Peña, Ike; Lee, Jong Chan; Lee, Han Lim; Woo, Tae Seon; Lee, Hae Chang; Sohn, Aee Ree; Cheong, Jae Hoon

    2012-04-18

    Several questions remain unanswered concerning the effects of long-term methylphenidate treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). It has been speculated that repeated methylphenidate treatment may facilitate abuse of the drug or psychological dependence. In the present study, we conducted conditioned place preference (CPP) tests to investigate whether the repeated treatment of methylphenidate results to greater "liking" of the drug. We compared the effect of methylphenidate with that of methamphetamine, a drug with high abuse and dependence liability; also used as a treatment of ADHD. Prior to CPP tests, adolescent spontaneously hypertensive rats (SHR) (putative rodent model of ADHD) and Wistar rats (strain used to represent the "normal" heterogeneous population) were administered intraperitoneally with methylphenidate (1.25, 5 and 20 mg/kg) or methamphetamine (1.25 and 5 mg/kg) for 14 days in their home cages. CPP tests were commenced and rats were conditioned with the two stimulants at the doses stated. We found that (1) repeated administration of methylphenidate and methamphetamine was rewarding in Wistar rats (2) stimulant-treated SHR showed CPP only to methamphetamine but not to methylphenidate. The observation that Wistar rats, but not SHR showed CPP to methylphenidate indicates vulnerability of "normal" individuals to methylphenidate abuse and dependence following repeated exposure or administration of the drug. The findings in SHR suggest the safety of methylphenidate as an ADHD intervention insofar as its behavioral effects are compared with those of methamphetamine, and to the extent that the SHR appropriately models ADHD in humans.

  4. Methamphetamine use in urban gay and bisexual populations.

    PubMed

    Shoptaw, Steven

    2006-01-01

    It is estimated that the use of methamphetamine is 5- to 10-times more common in urban gay and bisexual men than in the general US population. Given its effects in stimulating energy, confidence, and libido, as well as its relative inexpensiveness, the drug can efficiently address serious problems in functioning among HIV-infected men, who may suffer significant symptoms of depression or fatigue associated with chronic illness and HIV-related drug treatments. Long-term methamphetamine use is associated with physical, psychologic, and social adverse effects. Increased use of the drug associates with more frequent sexual risk behaviors and increased risks for HIV transmission. Behavioral therapies, notably the approach of contingency management, are being investigated for reducing methamphetamine use and risk behaviors in the urban gay population.

  5. Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects.

    PubMed

    Adinoff, Bryon; Devous, Michael D; Williams, Mark J; Harris, Thomas S; Best, Susan E; Dong, Hongyun; Zielinski, Tanya

    2014-03-01

    5-hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal dopaminergic transmission and have been implicated in the pathophysiology of cocaine reward, withdrawal and self-administration. In addition, the 5HT3 antagonist ondansetron is effective in treating early-onset, but not late-onset, alcohol-dependent subjects. To explore the role of 5HT3 receptor systems in cocaine addiction using functioning imaging, we administered ondansetron to 23 abstinent, treatment-seeking cocaine-addicted and 22 sex-, age- and race-matched healthy control participants. Differences between early- (first use before 20 years, n = 10) and late-onset (first use after 20 years, n = 10) cocaine-addicted subjects were also assessed. On two separate days, subjects were administered ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional cerebral blood flow (rCBF) was measured following each infusion with single photon emission computed tomography. No significant rCBF differences between the cocaine-addicted and control participants were observed following ondansetron relative to saline. Early-onset subjects, however, showed increased (P < 0.001) right posterior parahippocampal rCBF following ondansetron. In contrast, late-onset subjects showed decreased rCBF following ondansetron in an overlapping region of the right parahippocampal/hippocampal gyrus. Early-onset subjects also displayed increased rCBF in the left anterior insula and subthalamic nucleus following ondansetron; late-onset subjects showed decreased rCBF in the right anterior insula. These findings suggest that the age of drug use onset is associated with serotonergic biosignatures in cocaine-addicted subjects. Further clarification of these alterations may guide targeted treatment with serotonergic medications similar to those successfully used in alcohol-dependent patients.

  6. Methamphetamine Regulation of Firing Activity of Dopamine Neurons.