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Sample records for methamphetamine dependent subjects

  1. 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

  2. Cognitive Control and White Matter Callosal Microstructure in Methamphetamine Dependent Subjects: A DTI Study

    PubMed Central

    Salo, Ruth; Nordahl, Thomas E; Buonocore, Michael H; Natsuaki, Yutaka; Waters, Christy; Moore, Charles D; Galloway, Gantt P; Leamon, Martin H

    2009-01-01

    Background Methamphetamine (MA) abuse causes damage to structures within the human cerebrum, with particular susceptibility to white matter (WM). Abnormalities have been reported in anterior regions with less evidence of changes in posterior regions. MA abusers have also shown deficits on attention tests that measure response conflict and cognitive control. Methods We examined cognitive control using a computerized measure of the Stroop selective attention task and indices of WM microstructure obtained from diffusion tensor imaging (DTI) in the callosal genu and splenium of 37 currently abstinent MA abusers and 17 non-substance abusing controls. Measurements of Fractional Anisotropy (FA), apparent diffusion coefficient (ADC) of callosal fibers and diffusion tensor eigenvalues were obtained in all subjects. Results The MA abusers exhibited greater Stroop reaction time interference (i.e., reduced cognitive control) [p=.04] compared to controls. After correcting for multiple comparisons, FA within the genu correlated significantly with measures of cognitive control in the MA abusers [p=.04, bonferroni corrected] but not in controls [p=.26]. Group differences in genu, but not splenium, FA were trend significant [p=.09]. Conclusions MA abuse appears to alter anterior callosal WM microstructure with less evidence of change within posterior callosal WM microstructure. DTI indices within the genu, but not splenium, correlated with measures of cognitive control in chronic MA abusers. PMID:18814867

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

    PubMed Central

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

    2010-01-01

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

  4. Relationship of Alexithymia Ratings to Dopamine D2-type Receptors in Anterior Cingulate and Insula of Healthy Control Subjects but Not Methamphetamine-Dependent Individuals

    PubMed Central

    Okita, Kyoji; Ghahremani, Dara G.; Payer, Doris E.; Robertson, Chelsea L.; Mandelkern, Mark A.

    2016-01-01

    Background: Individuals with substance-use disorders exhibit emotional problems, including deficits in emotion recognition and processing, and this class of disorders also has been linked to deficits in dopaminergic markers in the brain. Because associations between these phenomena have not been explored, we compared a group of recently abstinent methamphetamine-dependent individuals (n=23) with a healthy-control group (n=17) on dopamine D2-type receptor availability, measured using positron emission tomography with [18F]fallypride. Methods: The anterior cingulate and anterior insular cortices were selected as the brain regions of interest, because they receive dopaminergic innervation and are thought to be involved in emotion awareness and processing. The Toronto Alexithymia Scale, which includes items that assess difficulty in identifying and describing feelings as well as externally oriented thinking, was administered, and the scores were tested for association with D2-type receptor availability. Results: Relative to controls, methamphetamine-dependent individuals showed higher alexithymia scores, reporting difficulty in identifying feelings. The groups did not differ in D2-type receptor availability in the anterior cingulate or anterior insular cortices, but a significant interaction between group and D2-type receptor availability in both regions, on self-report score, reflected significant positive correlations in the control group (higher receptor availability linked to higher alexithymia) but nonsignificant, negative correlations (lower receptor availability linked to higher alexithymia) in methamphetamine-dependent subjects. Conclusions: The results suggest that neurotransmission through D2-type receptors in the anterior cingulate and anterior insular cortices influences capacity of emotion processing in healthy people but that this association is absent in individuals with methamphetamine dependence. PMID:26657175

  5. [Genetic vulnerability of methamphetamine dependence].

    PubMed

    Moriya, Yuki; Kasahara, Yoshiyuki; Sora, Ichiro

    2013-08-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. 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 ...

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

    PubMed

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

    2009-10-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2000-01-01

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

  13. 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 ...

  14. Methamphetamine

    MedlinePlus

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

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

    PubMed Central

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

    2016-01-01

    Background Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. Method Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5) Results Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (p<0.005, threshold 15 voxels). Interestingly the ventral striatum activation significantly correlated with the days since the last use of meth (r=−0.76, p=0.017). No significant activity was found in healthy control group. Conclusion The preliminary data suggest that methamphetamine dependent subjects, when exposed to methamphetamine-associated visual cues, have increased brain activity in ventral striatum, caudate nucleus and medial frontal cortex which subserve craving, drug-seeking, and drug use. PMID:27314105

  16. 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.

  17. Association Between 5HT1b Receptor Gene and Methamphetamine Dependence

    PubMed Central

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

    2011-01-01

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

  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. Methamphetamine

    MedlinePlus

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  2. Effect of Methamphetamine Dependence on Heart Rate Variability

    PubMed Central

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

    2010-01-01

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

  3. Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals.

    PubMed

    Salo, Ruth; Nordahl, Thomas E; Possin, Kate; Leamon, Martin; Gibson, David R; Galloway, Gantt P; Flynn, Neil M; Henik, Avishai; Pfefferbaum, Adolf; Sullivan, Edith V

    2002-08-01

    Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others. PMID:12140121

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

    PubMed Central

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

    2013-01-01

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

  5. GLOBAL AND LOCAL MORPHOMETRIC DIFFERENCES IN RECENTLY ABSTINENT METHAMPHETAMINE-DEPENDENT INDIVIDUALS

    PubMed Central

    Schwartz, Daniel L.; Mitchell, Alex D.; Lahna, David L.; Luber, Hannah S.; Huckans, Marilyn S.; Mitchell, Suzanne H.; Hoffman, William F.

    2010-01-01

    Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to MA use history, length of abstinence and age of first use. Controls had greater density relative to MA in bilateral insula and left middle frontal gyrus. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 21) was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity. PMID:20096794

  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. PMID:25505562

  7. Methamphetamine causes acute hyperthermia-dependent liver damage

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  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. Randomized Trial of Intensive Motivational Interviewing for Methamphetamine Dependence

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-03-01

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

  12. 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. PMID:27043121

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

    PubMed

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

    2016-04-30

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Saika, Fumihiro; Kiguchi, Norikazu; Kishioka, Shiroh

    2015-10-01

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

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

    PubMed Central

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

    2011-01-01

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

  18. The acetylcholinesterase inhibitor rivastigmine does not alter total choices for methamphetamine, but may reduce positive subjective effects, in a laboratory model of intravenous self-administration in human volunteers.

    PubMed

    De La Garza, R; Mahoney, J J; Culbertson, C; Shoptaw, S; Newton, T F

    2008-04-01

    A human laboratory model of intravenous methamphetamine self-administration may facilitate study of putative treatments for methamphetamine addiction. We conducted a double-blind, placebo-controlled, between groups investigation of the acetylcholinesterase (AChE) inhibitor rivastigmine in non-treatment-seeking volunteers who met criteria for methamphetamine abuse or dependence. Safety and subjective effects data derived from days 1-10 of this protocol are described in a separate publication. In this report, we describe self-administration outcomes in participants randomized to treatment with rivastigmine (0 mg, N=7; 1.5 mg, N=6; 3 mg, N=9); data that were collected on days 11-15 of the inpatient protocol. On day 11, participants sampled two infusions of methamphetamine (0 and 30 mg, i.v.). On days 12-15, participants made ten choices each day to receive an infusion of either methamphetamine (3 mg, IV) or saline or a monetary alternative ($0.05-$16). The study design allowed for evaluation of differences in behavior on days in which infusions were performed by the physician (experimenter-administered) versus by the participant using a PCA pump (self-administered), and when monetary alternatives were presented in either ascending or descending sequence. The data show that rivastigmine (1.5 and 3 mg), as compared to placebo, did not significantly alter total choices for methamphetamine (p=0.150). Importantly, the number of infusion choices was greater when methamphetamine was available then when saline was available (p<0.0001), and the number of money choices was greater when saline was available then when methamphetamine was available (p<0.0001). The total number of choices for methamphetamine was not altered as a function of a participant's preferred route of methamphetamine use (p=0.57), and did not differ significantly whether they were experimenter-administered or self-administered (p=0.30). In addition, total choices for methamphetamine were similar made when

  19. 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…

  20. A double-blind, placebo-controlled study of N-acetyl cysteine plus naltrexone for methamphetamine dependence.

    PubMed

    Grant, Jon E; Odlaug, Brian L; Kim, Suck Won

    2010-11-01

    Reducing both glutamatergic and dopaminergic drive in the nucleus accumbens may offer complementary mechanisms by which to reduce drug cravings. This 8-week study sought to examine the efficacy of a combination of a glutamate modulator, N-acetyl cysteine (NAC), plus the opioid antagonist, naltrexone, compared to placebo in the treatment of methamphetamine dependence. Thirty-one subjects with methamphetamine dependence (mean age 36.8 ± 7.12 years; 29% female) were randomly assigned in a 1:1 fashion to NAC plus naltrexone or placebo and returned for one post-baseline visit. The Penn Craving Scale was the primary outcome measure. Self-report methamphetamine use frequency and urine toxicology were secondary measures. NAC plus naltrexone failed to demonstrate statistically significant differences from placebo on primary and secondary outcomes. The current study failed to demonstrate greater efficacy for NAC plus naltrexone compared to placebo. Given the small sample size, the statistical power to detect significant effects of active treatment versus placebo was limited. The question of whether a larger, well-powered sample would have detected differences between NAC plus naltrexone and placebo deserves further examination. PMID:20655182

  1. "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. PMID:24290100

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

    PubMed Central

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

    2016-01-01

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

  3. Personality Traits and Identity Styles in Methamphetamine-Dependent Women: A Comparative Study

    PubMed Central

    Hojjat, Seyed Kaveh; Golmakani, Ebrahim; Bayazi, Mohammad Hossein; Mortazavi, Razieh; Khalili, Mina Norozi; Akaberi, Arash

    2016-01-01

    Background: Studies over the past two decades have shown that various personality traits of substance-dependent men measure differently than compared to normal individuals. However fewer studies have addressed the role of identity as an influential factor in the onset and continuation of drug dependency. Methods: The objective of this study was to compare the Big Five personality factors and identity styles in methamphetamine dependent women and non-user group. Forty eight methamphetamine dependent women under treatment in Welfare Organization’s residential centers filled out the NEO Five-Factor Inventory (NEO-FFI) and the Berzonsky’s Identity Style Inventory. They were compared with 48 non-dependent women who were matched in terms of age, education, marital status, and occupation. Data was analyzed with t student test. Statistical analyses were performed using the SPSS V.16 software. Differences were considered significant at P<0.05. Results: Results found that methamphetamine dependent woman had significantly higher levels of neuroticism and lower levels of conscientiousness, agreeableness and openness to experience compared to normative sample of female respondents. In addition, mean scores of diffuse/avoidant identity style in methamphetamine user women was significantly higher than non-user group. This is while non-user women had a significantly higher mean in normative identity style. Conclusion: Identity styles along with personality traits can be a key role in drug use in women in this study. Therefore, enhancing understanding about the role of identity can be helpful in treatment programs especially in harm reduction approaches. PMID:26234975

  4. Overlapping Cognitive Patterns in Schizophrenia and Methamphetamine Dependence

    PubMed Central

    Salo, Ruth; Ravizza, Susan; Fassbender, Catherine

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. 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

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

    PubMed Central

    Saify, Khyber; Saadat, Mostafa

    2015-01-01

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

  8. A comparison of methamphetamine-dependent inpatients childhood attention deficit hyperactivity disorder symptomatology.

    PubMed

    Jaffe, Craig; Bush, Kristen R; Straits-Troster, Kristy; Meredith, Charles; Romwall, Lisa; Rosenbaum, Gail; Cherrier, Monique; Saxon, Andrew J

    2005-01-01

    Methamphetamine-dependent inpatients (N = 51) were screened for childhood attention deficit hyperactivity disorder (ADHD) using the Wender Utah Rating Scale upon admission to 30-day inpatient treatment. Baseline assessments included neuropsychological tests of executive function, memory, information processing, verbal fluency, attention, motor skills, and the Brief Symptom Inventory (BSI), a measure of psychiatric symptomatology. The thirty-six participants (70.6%) screening positive for ADHD reported significantly more frequent methamphetamine use prior to baseline. Baseline cognitive functioning was similar between groups, but the presumptive ADHD participants exhibited significantly worse psychiatric symptomatology. At three-week follow- up, 41 participants (80.4%) repeated the neuropsychological battery and BSI. All 10 non-completers screened positive for ADHD. The entire sample improved with abstinence in most neuropsychological domains except memory. The presumptive ADHD group failed to improve on tests of attention. All participants demonstrated significant reductions in psychiatric symptoms with abstinence. Methamphetamine-dependent individuals with ADHD symptoms are common and pose a significant treatment challenge. PMID:16186089

  9. Effect of modafinil on learning and task-related brain activity in methamphetamine-dependent and healthy individuals.

    PubMed

    Ghahremani, Dara G; Tabibnia, Golnaz; Monterosso, John; Hellemann, Gerhard; Poldrack, Russell A; London, Edythe D

    2011-04-01

    Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function. Therefore, medications that improve cognition in these subjects may improve the success of therapy for their addiction, especially when cognitive behavioral therapies are used. Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers. We therefore conducted a randomized, double-blind, placebo-controlled, cross-over study, using functional magnetic resonance imaging, to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent, MA-dependent, and healthy control participants. Modafinil (200 mg) and placebo were administered orally (one single dose each), in counterbalanced fashion, 2 h before each of two testing sessions. Under placebo conditions, MA-dependent participants showed worse learning performance than control participants. Modafinil boosted learning in MA-dependent participants, bringing them to the same performance level as control subjects; the control group did not show changes in performance with modafinil. After controlling for performance differences, MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants. The findings suggest that modafinil improves learning in MA-dependent participants, possibly by enhancing neural function in regions important for learning and cognitive control. These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence. PMID:21289606

  10. Subjective and Cardiovascular Effects of Intravenous Methamphetamine during Perindopril Maintenance: A Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

    PubMed Central

    Haile, Colin N.; De La Garza, Richard; Grasing, Kenneth; Kosten, Thomas R.; Newton, Thomas F.

    2016-01-01

    Background: Our pilot study suggested that the angiotensin-converting enzyme inhibitor perindopril might reduce some subjective effects produced by i.v. methamphetamine. We characterized the impact of a wider range of perindopril doses on methamphetamine-induced effects in a larger group of non-treatment-seeking, methamphetamine-using volunteers. Methods: Before treatment, participants received 30mg methamphetamine. After 5 to 7 days of perindopril treatment (0, 4, 8, or 16mg/d), participants received 15 and 30mg of methamphetamine on alternate days. Before and after treatment, participants rated subjective effects and cardiovascular measures were collected. Results: Prior to treatment with perindopril, there were no significant differences between treatment groups on maximum or peak subjective ratings or on peak cardiovascular effects. Following perindopril treatment, there were significant main effects of treatment on peak subjective ratings of “anxious” and “stimulated”; compared to placebo treatment, treatment with 8mg perindopril significantly reduced peak ratings of both anxious (P=.0009) and stimulated (P=.0070). There were no significant posttreatment differences between groups on peak cardiovascular effects. Conclusions: Moderate doses of perindopril (8mg) significantly reduced peak subjective ratings of anxious and stimulated as well as attenuated many other subjective effects produced by methamphetamine, likely by inhibiting angiotensin II synthesis. Angiotensin II is known to facilitate the effects of norepinephrine, which contributes to methamphetamine’s subjective effects. The lack of a classic dose-response function likely results from either nonspecific effects of perindopril or from between-group differences that were not accounted for in the current study (i.e., genetic variations and/or caffeine use). The current findings suggest that while angiotensin-converting enzyme inhibitors can reduce some effects produced by methamphetamine

  11. 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

  12. Methamphetamine overdose

    MedlinePlus

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

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

    PubMed

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

    2016-06-01

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

  14. Intensive Motivational Interviewing for women with concurrent alcohol problems and methamphetamine dependence

    PubMed Central

    Polcin, Douglas L.; Evans, Kristy; Bond, Jason C.; Galloway, Gantt P.

    2013-01-01

    Motivational interviewing (MI) for the treatment of alcohol and drug problems is typically conducted over 1 to 3 sessions. The current work evaluates an intensive 9-session version of MI (Intensive MI) compared to a standard single MI session (Standard MI) using 163 methamphetamine (MA) dependent individuals. The primary purpose of this paper is to report the unexpected finding that women with co-occurring alcohol problems in the Intensive MI condition reduced the severity of their alcohol problems significantly more than women in the Standard MI condition at the 6-month follow-up. Stronger perceived alliance with the therapist was inversely associated with alcohol problem severity scores. Findings indicate that Intensive MI is a beneficial treatment for alcohol problems among women with MA dependence. PMID:24074649

  15. Altered Cingulate and Insular Cortex Activation During Risk-Taking in Methamphetamine Dependence: Losses Lose Impact

    PubMed Central

    Gowin, Joshua L.; Stewart, Jennifer L.; May, April C.; Ball, Tali M.; Wittmann, Marc; Tapert, Susan F.; Paulus, Martin P.

    2013-01-01

    Aims To determine if methamphetamine-dependent (MD) individuals exhibit behavioral or neural processing differences in risk-taking relative to healthy comparison participants (CTL). Design This was a cross-sectional study comparing two groups’ behavior on a risk-taking task and neural processing as assessed using functional magnetic resonance imaging (fMRI). Settings The study was conducted in an inpatient treatment center and a research fMRI facility in the United States. Participants Sixty-eight recently abstinent MD individuals recruited from a treatment program and forty CTL recruited from the community completed the study. Measurements The study assessed risk-taking behavior (overall and post-loss) using the Risky Gains Task (RGT), sensation-seeking, impulsivity and blood-oxygenation level dependent activation in the brain during the decision phase of the RGT. Findings Relative to CTL, MD displayed decreased activation in the bilateral rostral anterior cingulate cortex (ACC) and greater activation in the left insula across risky and safe decisions (p<.05). Right mid insula activation among CTL did not vary between risky and safe decisions, but among MD it was higher during risky relative to safe decisions (p<.05). Among MD, lower activation in the right rostral ACC (r=−.39, p<.01) and higher activation in the right mid insula (r=.35, p<.01) during risky decisions were linked to a higher likelihood of choosing a risky option following a loss. Conclusions Methamphetamine-dependent individuals show disrupted risk-related processing in both anterior cingulate and insula, brain areas that have been implicated in cognitive control and interoceptive processing. Attenuated neural processing of risky options may lead to risk-taking despite experiencing negative consequences. PMID:24033715

  16. 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. PMID:26751259

  17. A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia.

    PubMed

    Morita, Yukitaka; Ujike, Hiroshi; Tanaka, Yuji; Uchida, Naohiko; Nomura, Akira; Ohtani, Kyohei; Kishimoto, Makiko; Morio, Akiko; Imamura, Takaki; Sakai, Ayumu; Inada, Toshiya; Harano, Mutsuo; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sekine, Yoshimoto; Iwata, Nakao; Iyo, Masaomi; Sora, Ichiro; Ozaki, Norio; Kuroda, Shigetoshi

    2005-03-16

    Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia. PMID:15721218

  18. 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. PMID:25081313

  19. 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

  20. Methamphetamine: Glossary

    MedlinePlus

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

  1. 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

  2. The Body Mass Index, Blood Pressure, and Fasting Blood Glucose in Patients With Methamphetamine Dependence.

    PubMed

    Lv, Dezhao; Zhang, Meijuan; Jin, Xuru; Zhao, Jiyun; Han, Bin; Su, Hang; Zhang, Jie; Zhang, Xiangyang; Ren, Wenwei; He, Jincai

    2016-03-01

    Methamphetamine (MA) is a prevalently abused psychostimulant in the world. Previously published studies and case reports indicated potential associations between MA and body mass index (BMI) and cardiovascular factors (eg, blood pressure and fasting blood glucose). However, these associations have not been studied clearly. This study aimed to investigate BMI and cardiovascular factors in the MA-dependent patients.A total of 1019 MA-dependent patients were recruited between February 2, 2008 and March 11, 2013. A case report was used to gather information on sociocharacteristics and drug-dependent history. Meanwhile, a number of 1019 age- and sex-matched controls' information were collected from the physical examination center. We measured BMI, blood pressure, and fasting blood glucose among the participants.MA-dependent patients had significantly lower BMI (20.4 ± 0.1 vs 23.9 ± 0.1 kg/m, P < 0.001), lower fasting blood glucose (5.0 ± 0.01 vs 5.2 ± 0.01 mmol/L, P < 0.001) and higher systolic blood pressure (122.1 ± 0.4 vs 114.8 ± 0.4 mmHg, P < 0.001) compared with the control group after adjustment of possible confounders. Additional, we only found the duration of MA use was independently associated with BMI (B = -0.08, P = 0.04).This study demonstrated that MA dependence was associated with BMI and cardiovascular factors. In addition, we found a negative association between duration of MA use and BMI. PMID:27015198

  3. 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. PMID:25054922

  4. 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

  5. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

    PubMed Central

    Shoptaw, Steven; Heinzerling, Keith G.; Rotheram-Fuller, Erin; Steward, Trevor; Wang, Jason; Swanson, Aimee-Noelle; De La Garza, Richard; Newton, Tom; Ling, Walter

    2013-01-01

    Objective To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. Methods Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice 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 measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions. Results There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0–2 MA-positive urines), but not heavier (3–6 MA-positive urines) MA use during baseline (OR=2.81, 95% CI=1.61–4.93, p<0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost 5 cigarettes per day (p=0.0002). Conclusion Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light MA users is warranted. PMID:18468815

  6. 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. PMID:25801501

  7. Visual Memory in Methamphetamine Dependent Individuals: Deficient Strategic Control of Encoding and Retrieval

    PubMed Central

    Morgan, Erin E.; Woods, Steven Paul; Poquette, Amelia J.; Vigil, Ofilio; Heaton, Robert K.; Grant, Igor

    2012-01-01

    Objective Chronic use of methamphetamine (MA) has moderate effects on neurocognitive functions associated with frontal systems, including the executive aspects of verbal episodic memory. Extending this literature, the current study examined the effects of MA on visual episodic memory with the hypothesis that a profile of deficient strategic encoding and retrieval processes would be revealed for visuospatial information (i.e., simple geometric designs), including possible differential effects on source versus item recall. Method The sample comprised 114 MA-dependent (MA+) and 110 demographically-matched MA-nondependent comparison participants (MA−) who completed the Brief Visuospatial Memory Test – Revised (BVMT-R), which was scored for standard learning and memory indices, as well as novel item (i.e., figure) and source (i.e., location) memory indices. Results Results revealed a profile of impaired immediate and delayed free recall (p < .05) in the context of preserved learning slope, retention, and recognition discriminability in the MA+ group. The MA+ group also performed more poorly than MA− participants on Item visual memory (p < .05) but not Source visual memory (p > .05), and no group by task-type interaction was observed (p > .05). Item visual memory demonstrated significant associations with executive dysfunction, deficits in working memory, and shorter length of abstinence from MA use (p < 0.05). Conclusions These visual memory findings are commensurate with studies reporting deficient strategic verbal encoding and retrieval in MA users that are posited to reflect the vulnerability of frontostriatal circuits to the neurotoxic effects of MA. Potential clinical implications of these visual memory deficits are discussed. PMID:22311530

  8. 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…

  9. 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. PMID:26844469

  10. 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

  11. 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

  12. Hair analysis for drugs of abuse. VI. The excretion of methoxyphenamine and methamphetamine into beards of human subjects.

    PubMed

    Nakahara, Y; Takahashi, K; Konuma, K

    1993-12-01

    The excretion of methoxyphenamine (MOP) and methamphetamine (MA) into beards has been studied. Six healthy male subjects orally took 50 mg of MOP at a single dose and 7 doses for a successive 7 days. Their beard hairs were collected by an electric shaver every morning until MOP disappeared from the beard. After washing with 0.1% SDS, the beard samples were extracted with methanol-5 N HCl (20:1) under ultra-sonication for 1 h and the solution was kept overnight. MOP in the extract was determined by GC/MS using deuterium labelled MOP as an internal standard after trifluoroacetyl-derivatization. The drug concentrations in beard and the reproducibility of analysis were compared with the three procedures, unwashed, 0.1% SDS (wash I) and the additional ethanol (wash II) wash. The drug concentration in beard after SDS wash was 0.5-2.5 ng/mg lower than that in unwashed beard during the first 5-6 days. The drug concentration in beard after ethanol wash was much lower than that in the unwashed beard. The drug excreted into beard was detected 10 approximately 12 days for a single dose and 12-14 days for 7 doses after the last dosage at the cut off level of 1 ng/mg. On the contrary, the drug excreted in urine was not detected after more than 3 days after use. O-Desmethyl MOP, a major metabolite of MOP, was also detected in beard. The procedures were applied to the detection of MA in beard of MA abusers. It was realized that a beard sample was more useful than a urine sample assuming a longer detection. PMID:7908007

  13. Methamphetamine induces the release of endothelin.

    PubMed

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

    2016-02-01

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

  14. Methamphetamine overdose

    MedlinePlus

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

  15. Methamphetamine (Meth)

    MedlinePlus

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

  16. Methamphetamine Cured my Cocaine Addiction.

    PubMed

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

    2010-10-14

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

  17. Methamphetamine Cured my Cocaine Addiction

    PubMed Central

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

    2011-01-01

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

  18. 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

  19. The Clinical Pharmacology of Intranasal l-Methamphetamine

    PubMed Central

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

    2008-01-01

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

  20. The cortisol level and its relationship with depression, stress and anxiety indices in chronic methamphetamine-dependent patients and normal individuals undergoing inguinal hernia surgery

    PubMed Central

    Pirnia, Bijan; Givi, Fatemeh; Roshan, Rasool; Pirnia, Kambiz; Soleimani, Ali Akbar

    2016-01-01

    Background: Stimulants addition and abuse can cause some functional and morphological changes in the normal function of glands and hormones. Methamphetamine as an addictive stimulant drug affects the Hypothalamic- pituitary-adrenal (HPA) axis and consequently makes some changes in the psychological state of the drug users. The present study aims to examine the relationship between plasma levels of cortisol with depression, stress and anxiety symptoms in chronic methamphetamine-dependent patients and normal individuals who have undergone the inguinal hernia surgery. Methods: To meet the purpose of the study, 35 chronic methamphetamine-dependent patients in the active phase of drug abuse and 35 non-users (N=70) who were homogenized regarding the demographic features were purposefully selected from among the patients referred to undergo inguinal hernia surgery since March 15 to June 9, 2015. The participants were then divided into the control and experiment group. The changes in cortisol levels in plasma were measured using Radioimmunoassay (RIA) in three-time series including 0 (upon the induction of anesthesia), 12 and 24 hours after the surgery. Further, three behavioral indices of depression, anxiety and stress were measured using the Depression Anxiety Stress Scale 21 (DASS-21) and then the data were analyzed using t-test and Pearson Correlation coefficient. Results: The plasma level of cortisol in the chronic methamphetamine-dependent patients (experiment group) had a significant increase in 24 hours after surgery (p<0.05). This study showed that cortisol levels in chronic methamphetamine-dependent patients were significantly higher than non-dependent patients in response to alarming events such as inguinal surgery. Changes in cortisol levels were intensified due to a confrontation with the phenomenon of pain and anxiety. In addition, depression index was higher in the chronic methamphetaminedependent patients than that in the non-dependent patients. However

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

    PubMed

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

    2007-09-01

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

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

    PubMed Central

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

    2009-01-01

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

  3. 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.

  4. Mind Over Matter: Methamphetamine

    MedlinePlus

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

  5. Fronto-temporal alterations and affect regulation in methamphetamine dependence with and without a history of psychosis.

    PubMed

    Uhlmann, Anne; Fouche, Jean-Paul; Koen, Nastassja; Meintjes, Ernesta M; Wilson, Don; Stein, Dan J

    2016-02-28

    Methamphetamine (MA) has been shown to have neurotoxic effects associated with brain structure changes and schizophrenia-like psychotic symptoms. Although these abnormalities may in turn be related to cognitive impairment and increased aggression, their association with affect dysregulation is less well studied. We investigated cortical thickness and subcortical volumes in 21 participants with MA dependence, 19 patients with MA-associated psychosis (MAP), and 19 healthy controls. Participants' affect regulation abilities were assessed through self-report scales on emotion reactivity (ERS) and difficulties in emotion regulation (DERS) and correlated with differences in cortical thickness. MAP patients showed thinner cortices in the fusiform and inferior temporal gyrus (ITG), orbitofrontal (OFC) and inferior frontal gyrus (IFG), and insula, compared to the MA group. MAP also showed significantly lower hippocampal volumes relative to MA and CTRL. Both clinical groups showed impairment in affect regulation, but only in MAP was this dysfunction associated with thinner cortices in ITG, OFC and IFG. Our findings suggest significant differences in cortical thickness in MA dependence with and without psychosis. Lower fronto-temporal cortical thickness and smaller hippocampal volumes in MAP are consistent with neuroimaging findings in other psychotic disorders, supporting the notion of MAP being a useful model of psychosis. PMID:26792587

  6. Differences in cortical activity between methamphetamine-dependent and healthy individuals performing a facial affect matching task.

    PubMed

    Payer, Doris E; Lieberman, Matthew D; Monterosso, John R; Xu, Jiansong; Fong, Timothy W; London, Edythe D

    2008-01-11

    As individuals who abuse methamphetamine (MA) often exhibit socially maladaptive behaviors such as violence and aggression, it is possible that they respond abnormally to social cues. To investigate this issue, we exposed 12 MA-dependent participants (abstinent 5-16 days) and 12 healthy comparison participants to fearful and angry faces while they performed an affect matching task during functional magnetic resonance imaging (fMRI). Although the groups did not differ in task performance, the healthy participants showed more task-related activity than the MA-dependent participants in a set of cortical regions consisting of the ventrolateral prefrontal cortex (VLPFC), temporoparietal junction (TPJ), anterior and posterior temporal cortex, and fusiform gyrus in the right hemisphere, and the cuneus in the left hemisphere. In contrast, the MA-dependent participants showed more task-related activity than the healthy participants in the dorsal anterior cingulate cortex (dACC). As expected, the task elicited activation of the amygdala in both groups; however, contrary to expectation, we found no difference between groups in this activation. Dorsal ACC hyperactivity, along with high self-ratings of hostility and interpersonal sensitivity in the MA-dependent group, suggest a hyper-sensitivity to socially threatening cues in the MA-dependent participants, while lower VLPFC activation could point to a deficit in integrating socio-emotional information and/or regulating this limbic hyperactivity. Additional activation differences in neural circuitry related to social cognition (TPJ, anterior, and posterior temporal cortex) suggest further socio-emotional deficits. Together, the results point to cortical abnormalities that could underlie the socially inappropriate behaviors often shown by individuals who abuse MA. PMID:17964741

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

    PubMed Central

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

    2012-01-01

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

  8. Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats

    PubMed Central

    Herring, Nicole R; Schaefer, Tori L; Tang, Peter H; Skelton, Matthew R; Lucot, James P; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

    2008-01-01

    Background Methamphetamine (MA) use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+)-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+)-MA (4 doses at 2 h intervals) on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session) 4 times at 2 h intervals]. Results MA increased corticosterone from 1–72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h. Conclusion Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone. PMID:18513404

  9. 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

  10. 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

  11. Advantages of Joint Modeling of Component HIV Risk Behaviors and Non-Response: Application to Randomized Trials in Cocaine-Dependent and Methamphetamine-Dependent Populations

    PubMed Central

    Holmes, Tyson H.; Anderson, Ann L.; Li, Shou-Hua; Elkashef, Ahmed M.

    2011-01-01

    The HIV risk-taking behavior scale (HRBS) is an 11-item instrument designed to assess the risks of HIV infection due to self-reported injection-drug use and sexual behavior. A retrospective analysis was performed on HRBS data collected from approximately 1,000 participants pooled across seven clinical trials of pharmacotherapies for either the treatment of cocaine dependence or methamphetamine dependence. Analysis faced three important challenges. The sample contained a high proportion of missing assessments after randomization. Also, the HRBS scale consists of two distinct behavioral components which may or may not coincide in response patterns. In addition, distributions of responses on the subscales were highly concentrated at just a few values (e.g., 0, 6). To address these challenges, a single probit regression model was fit to three outcomes variables simultaneously – the two subscale totals plus an indicator variable for assessments not obtained (non-response). This joint-outcome regression model was able to identify that those who left assessment early had higher self-reported risk of injection-drug use and lower self-reported risky sexual behavior because the model was able to draw on information on associations among the three outcomes collectively. These findings were not identified in analyses performed on each outcome separately. No evidence for an effect of pharmacotherapies was observed, except to reduce missing assessments. Univariate-outcome modeling is not recommended for the HRBS. PMID:21779253

  12. 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

  13. 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. PMID:26275348

  14. 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

  15. Research Reports: Methamphetamine

    MedlinePlus

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

  16. Association between the Regulator of G-protein Signaling 9 Gene and Patients with Methamphetamine Use Disorder and Schizophrenia

    PubMed Central

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

    2011-01-01

    The regulator of G-protein signaling (RGS) modulates the functioning of heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a role in modulating dopaminergic receptor-mediated signaling cascades. Previous studies suggested that the RGS9 gene might contribute to the susceptibility to psychotic diseases. Therefore, we investigated the association between the RGS9 gene and two related dopamine psychoses, schizophrenia and methamphetamine use disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and sex-matched healthy controls and 220 patients of methamphetamine use disorder and 289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285 (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed monomorphism in the present Japanese population, but rs12452285 showed polymorphism. There were no significant differences in genotypic or allelic distributions of rs12452285 between patients with schizophrenia and the corresponding control or between patients with methamphetamine use disorder and the corresponding control. We also analyzed the clinical features of methamphetamine use disorder. We found a significant association in allelic distribution with the phenotypes of age at first consumption (p=0.047). The present study suggested that the RGS9 gene is unlikely to play a major role in schizophrenia and methamphetamine dependence liability and/or the development of methamphetamine induced psychosis, at least in a Japanese population. PMID:21886588

  17. 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…

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

    PubMed

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

    2010-08-01

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

  19. Risky Decision-making: Prefrontal Function and Mesocorticolimbic Resting-state Connectivity in Methamphetamine Users

    PubMed Central

    Kohno, Milky; Morales, Angelica M.; Ghahremani, Dara G.; Hellemann, Gerhard; London, Edythe D.

    2014-01-01

    Importance Various neuropsychiatric disorders, especially addictions, feature impairments in risky decision-making; clarifying the neural mechanisms underlying this problem can inform treatment. Objective To determine how methamphetamine-dependent and control subjects differ in brain activation during a risky decision-making task, resting-state functional connectivity within mesolimbic and executive control circuits, and the relationships between these measures. Design A case-control, functional magnetic resonance imaging study of methamphetamine-dependent and healthy comparison participants at rest and when performing the Balloon Analogue Risk Task, which involves the choice to pump a balloon or to cash out in the context of uncertain risk. Setting Clinical research center at an academic institution. Participants Twenty-five methamphetamine-dependent and 27 control subjects. Main Outcomes and Measures 1) Parametric modulation of activation in the striatum and right dorsolateral prefrontal cortex, i.e., the degree to which activation changed as a linear function of risk and potential reward, both indexed by pump number; and 2) resting-state functional connectivity, measured in whole brain with seeds in the midbrain and right dorsolateral prefrontal cortex. Relationships between these outcomes were also tested. Results Parametric modulation of cortical and striatal activation by pump number during risk-taking differed with group. It was stronger in the ventral striatum but weaker in the right dorsolateral prefrontal cortex in methamphetamine-dependent participants than controls. Methamphetamine-dependent subjects also exhibited greater resting-state functional connectivity of the midbrain with the putamen, amygdala, and hippocampus. This connectivity was negatively related to modulation of right dorsolateral prefrontal cortex activation by risk level during risky decision-making. In controls, parametric modulation of right dorsolateral prefrontal cortex activation

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

    PubMed

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

    2016-03-01

    Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders. PMID:26736037

  1. The Hepatocyte Growth Factor/c-Met Antagonist, Divalinal-Angiotensin IV, Blocks the Acquisition of Methamphetamine Dependent Conditioned Place Preference in Rats

    PubMed Central

    Wright, John W.; Wilson, Wendy L.; Wakeling, Vanessa; Boydstun, Alan S.; Jensen, Audrey; Kawas, Leen; Harding, Joseph W.

    2012-01-01

    The use of methamphetamine (MA) is increasing in the U.S. and elsewhere around the world. MA’s capacity to cause addiction significantly exceeds other psychostimulant drugs, and its use negatively impacts learning and memory. Recently, attempts have been made to interfere with the presumed mechanism(s) underlying the establishment of drug-induced memory consolidation. The majority of these studies have employed matrix metalloproteinase (MMP) inhibitors to disrupt MMP-induced extracellular matrix molecule dependent synaptic reconfiguration, or GABA receptor agonists. The present investigation utilized an angiotensin IV (AngIV) analogue, Divalinal-AngIV (divalinal), to disrupt acquisition of MA-induced dependence in rats as measured using the conditioned place preference paradigm. Results indicate that both acute and chronic intracerebroventricular infusion of divalinal prior to each daily subcutaneous injection of MA prevented acquisition. However, divalinal was unable to prevent MA-induced reinstatement after prior acquisition followed by extinction trials. These results indicate that prevention of MA dependence can be accomplished by blockade of the brain AT4 receptor subtype. On the other hand, once MA-induced memory consolidation is in place divalinal appears to be ineffective. Mechanistic studies indicated that divalinal is a potent inhibitor of the hepatocyte growth factor (HGF)/c-Met receptor system, and thus it appears that a functional HGF/c-Met system is required for the acquisition of MA-mediated conditioned place preference. PMID:24961196

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

    PubMed Central

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

    2008-01-01

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

  3. Pharmacotherapy of methamphetamine addiction: an update.

    PubMed

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

    2008-01-01

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

  4. Pharmacotherapy of Methamphetamine Addiction: An Update

    PubMed Central

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

    2008-01-01

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

  5. Methamphetamine-Enhanced Female Sexual Motivation is Dependent on Dopamine and Progesterone Signaling in the Medial Amygdala

    PubMed Central

    Holder, Mary K.; Veichweg, Shaun S.; Mong, Jessica A.

    2014-01-01

    Methamphetamine (METH) is a psychomotor stimulant strongly associated with increases in sexual drive and impulsive sexual behaviors that often lead to unsafe sexual practices. In women METH users, such practices have been associated with increases in unplanned pregnancies and sexually transmitted diseases. Despite this significant heath concern, the neural mechanisms underlying this drug-sex association are not known. We previously established a rodent model of METH-facilitated female sexual behavior in which estradiol and progesterone interact with METH to increase motivational components of female behavior and neuronal activation in the posterodorsal medial amygdala (MePD) (Holder et al., 2010; Holder and Mong, 2010). The current study more directly examines the mechanisms underlying the drug-sex interaction. Here, we hypothesize that METH-induced increases in MePD dopamine signaling bridge the METH-hormone interaction. In support of this hypothesis, we found that excitotoxic lesions targeted to the MePD attenuated the METH-induced increases in proceptive behavior. Furthermore, infusion of a D1 agonist into the MePD increased proceptive behavior, while infusion of a D1 antagonist blocked the ability of METH to increase proceptive behaviors. Additionally, we found that METH-treatment increased progesterone receptor (PR)- immunoreactivity in the MePD, suggesting an interaction between dopamine and progesterone signaling. Indeed, infusions of the PR antagonist, RU486, prevented METH-induced increases in sexual behavior. Thus, taken together, the current findings suggest dopamine in the MePD modulates enhanced sexual motivation via an amplification of progesterone signaling and contributes to a better understanding of the neurobiology of drug-enhanced sexual behaviors. PMID:25448531

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

    PubMed Central

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

    2012-01-01

    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 0.03 mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3 – 10 mg/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. PMID:23010423

  7. 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

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

    PubMed

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

    2016-09-01

    Methamphetamine abuse remains an alarming public heath challenge, with no approved pharmacotherapies available. Agmatine is a naturally occurring cationic polyamine that has previously been shown to attenuate the rewarding and psychomotor-sensitizing effects of methamphetamine. This study examined the effects of agmatine on the discriminative stimulus and hyperthermic effects of methamphetamine. Adult male rats were trained to discriminate 0.32 mg/kg methamphetamine from saline. Methamphetamine dose dependently increased drug-associated lever responding. The nonselective dopamine receptor antagonist haloperidol (0.1 mg/kg) significantly attenuated the discriminative stimulus effects of methamphetamine (5.9-fold rightward shift). Agmatine (10-100 mg/kg) did not substitute for methamphetamine, but significantly attenuated the stimulus effects of methamphetamine, leading to a maximum of a 3.5-fold rightward shift. Acute 10 mg/kg methamphetamine increased the rectal temperature by a maximum of 1.96±0.17°C. Agmatine (10-32 mg/kg) pretreatment significantly attenuated the hyperthermic effect of methamphetamine. Agmatine (10 mg/kg) also significantly reversed methamphetamine-induced temperature increase. Together, these results support further exploration of the value that agmatine may have for the treatment of methamphetamine abuse and overdose. PMID:27232669

  9. Neurochemical Alterations in Methamphetamine-Dependent Patients Treated with Cytidine-5′-Diphosphate Choline: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

    PubMed Central

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

    2010-01-01

    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 (1H-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 1H-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. PMID:20043005

  10. 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

  11. A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence

    PubMed Central

    Shen, Hui; Mohammad, Adeel; Ramroop, Johnny; Smith, Sheryl S.

    2013-01-01

    Methamphetamine (METH) is an addictive stimulant drug. In addition to drug craving and lethargy, METH withdrawal is associated with stress-triggered anxiety. However, the cellular basis for this stress-triggered anxiety is not understood. The present results suggest that during METH withdrawal (24 h) following chronic exposure (3 mg/kg, i.p. for 3-5 weeks) of adult, male mice, the effect of one neurosteroid released by stress, 3α,5α-THP (3α-OH-5α-pregnan-20-one), and its 3α,5β isomer reverse to trigger anxiety assessed by the acoustic startle response (ASR), in contrast to their usual anti-anxiety effects. This novel effect of 3α,5β-THP was due to increased (3-fold) hippocampal expression of α4βδ GABAA receptors (GABARs) during METH withdrawal (24 h – 4 wk) because anxiogenic effects of 3α,5β-THP were not seen in α4−/− mice. 3α,5β-THP reduces current at these receptors when it is hyperpolarizing, as observed during METH withdrawal. As a result, 3α,5β-THP (30 nM) increased neuronal excitability, assessed with current clamp and cell-attached recordings in CA1 hippocampus, one CNS site which regulates anxiety. α4βδ GABARs were first increased 1 h after METH exposure and recovered 6 wk after METH withdrawal. Similar increases in α4βδ GABARs and anxiogenic effects of 3α,5β-THP were noted in rats during METH withdrawal (24 h). In contrast, the ASR was increased by chronic METH treatment in the absence of 3α,5β-THP administration due to its stimulant effect. Although α4βδ GABARs were increased by chronic METH treatment, the GABAergic current recorded from hippocampal neurons at this time was a depolarizing, shunting inhibition, which was potentiated by 3α,5β-THP. This steroid reduced neuronal excitability and anxiety during chronic METH treatment, consistent with its typical effect. Flumazenil (10 mg/kg, i.p., 3x) reduced α4βδ expression and prevented the anxiogenic effect of 3α,5β-THP after METH withdrawal. Our findings suggest

  12. 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

  13. 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

  14. 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…

  15. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

  16. The Cardiac Complications of Methamphetamines.

    PubMed

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

    2016-04-01

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

  17. 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

    2016-07-01

    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. PMID:27009763

  18. Neurobehavioral Effects from Developmental Methamphetamine Exposure.

    PubMed

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

    2016-01-01

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

  19. 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

  20. A Study of the Prevalence of Psychiatric Disorders in Patients with Methamphetamine-Induced Psychosis

    PubMed Central

    Eslami-Shahrbabaki, Mahin; Fekrat, Alireza; Mazhari, Shahrzad

    2015-01-01

    Background The abuse of narcotic drugs and psychotropic substances such as amphetamines and ecstasy has had a growing trend. Tachycardia, increased blood pressure, hallucinations, panic attacks, and psychosis are the negative effects of methamphetamine abuse. The present study aimed to assess psychiatric disorders associated with methamphetamine-induced psychotic disorder. Methods This cross-sectional study was performed from October 2013 to March 2014 on 165 patients hospitalized at Shahid Beheshti Hospital in Kerman, Iran, and diagnosed with psychosis induced by methamphetamine abuse within the previous 6 months. Study subjects were selected via census method. Based on the exclusion criteria and due to the lack of cooperation of some patients, 121 patients were enrolled in the study. Research data were gathered using clinical interviews, the Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton anxiety scale (HAM-A) and Hamilton rating scale for depression (HRSD), Young mania rating scale (YMRS), substance dependence severity scale (SDSS), positive and negative syndrome scale (PANSS), and clinical global impression (CGI) scale. The data analysis was performed using SPSS software, descriptive statistics, and ANOVA. Findings Among the 121 patients of the sample group, 4 patients (3.3%) had anxiety, 58 patients (47.9%) depression, 30 patients (24.8%) obsessive-compulsive disorder (OCD), 20 patients (16.5%) bipolar mood disorder (BMD), 8 patients (6.6%) persistent psychotic symptoms, 85 patients (70.2%) personality disorder, and 36 patients (29.8%) had no personality disorders. The highest prevalence was related to borderline personality disorder (35.5%). However, 45 patients (37.2%) had no impairment associated with methamphetamine-induced psychosis. Conclusion It seems that there is comorbidity between psychiatric disorders, including mood disorders, especially depressive disorder, childhood history of attention deficit hyperactivity disorder (ADHD), bipolar

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

    PubMed

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

    2016-02-15

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

  2. 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.…

  3. Perceived Risk of Methamphetamine among Chinese Methamphetamine Users

    PubMed Central

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

    2014-01-01

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

  4. 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

  5. The effects of adolescent methamphetamine exposure

    PubMed Central

    Buck, Jordan M.; Siegel, Jessica A.

    2015-01-01

    Methamphetamine use among adolescents is a significant social and public health concern. Despite increased awareness of methamphetamine use among younger people, relatively little research has examined the effects of adolescent methamphetamine use compared to adult use. Thus, much remains to be learned about how methamphetamine alters adolescent brain function and behavior. In this article we review recent trends in adolescent methamphetamine use and data examining the effects of adolescent methamphetamine use on the dopaminergic system and behavior in humans and animal models. Future research is warranted to expand our understanding of the effects of adolescent methamphetamine exposure and how those effects differ from those seen in adults. PMID:25972781

  6. 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

  7. 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. PMID:17010100

  8. Impulsivity and methamphetamine use.

    PubMed

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

    2005-09-01

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

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

    PubMed

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

    2015-05-01

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

  10. Predictors of methamphetamine psychosis: history of ADHD-relevant childhood behaviors and drug exposure.

    PubMed

    Salo, Ruth; Fassbender, Catherine; Iosif, Ana-Maria; Ursu, Stefan; Leamon, Martin H; Carter, Cameron

    2013-12-15

    The goal of this study was to extend our previous research that reported a significant association between Attention Deficit Hyperactivity Disorder (ADHD)-relevant childhood behaviors and the frequency of methamphetamine (MA)-induced psychotic symptoms in an expanded sample. 190 participants who met DSM-IV criteria for MA dependence were administered the Methamphetamine Experience Questionnaire that assessed MA-induced psychosis. Data related to MA exposure, comorbid drug use, education, familial psychiatric history and assessments of ADHD-relevant childhood behaviors as measured by the Wender Utah Rating Scale (WURS) were collected. Although WURS scores did not differ between 145 MAP+ and 45 MAP- subjects, MAP+ subjects with higher WURS scores were significantly more likely to report more frequent psychosis. Although mean daily MA dosage did not differ between the MAP+ and MAP- subjects, MAP+ subjects who consumed larger doses of MA were significantly more likely to experience frequent psychosis. These data suggest that ADHD-relevant childhood behaviors may interact with MA exposure to reflect a neurobiological vulnerability related to the emergence of frequent MA-induced psychotic symptoms. These results may elucidate factors that contribute to the psychiatric sequelae of MA abuse. PMID:23896355

  11. Duration Effects in Contingency Management Treatment of Methamphetamine Disorders

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    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 72kD) 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 wise-spread HSP expression in neural and glial cells examined in details 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. PMID:20931246

  13. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    MedlinePlus

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

  14. Methamphetamine Trends in the United States

    MedlinePlus

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

  15. 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" ...

  16. Prenatal Methamphetamine Exposure Linked with Problems

    MedlinePlus

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

  17. Methamphetamine: Putting the Brakes on Speed

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  18. Suicide Risk of Heroin Dependent Subjects in Lebanon.

    PubMed

    Kazour, François; Soufia, Michel; Rohayem, Jihane; Richa, Sami

    2016-07-01

    The aim is to determine the frequency of suicidal behavior and associated factors among heroin dependent inpatients. 61 heroin dependent inpatients (vs. 61 controls) were assessed on their pattern of substance use, impulsivity, depression and suicidal behavior. 37.7 % of patients had a personal history of suicidal attempt (SA), 14.8 % had current suicidal ideation. SA was associated to younger age at first substance use and to higher rates of depression and impulsivity. IV heroin overdose was the most frequent mode of SA (47.8 %). Long duration, multiple drug use, and family history of suicide were associated with higher risk of suicide among lebanese patients. PMID:26424734

  19. Maxillary sinus manifestations of methamphetamine abuse.

    PubMed

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

    2015-01-01

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

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

    PubMed

    Hensleigh, E; Pritchard, L M

    2014-07-15

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

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

    PubMed Central

    Hensleigh, E.; Pritchard, L. M.

    2014-01-01

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

  2. Reduced striatal dopamine transporter density associated with working memory deficits in opioid-dependent male subjects: a SPECT study.

    PubMed

    Liang, Chih-Sung; Ho, Pei-Shen; Yen, Che-Hung; Yeh, Yi-Wei; Kuo, Shin-Chang; Huang, Chang-Chih; Chen, Chun-Yen; Shih, Mei-Chen; Ma, Kuo-Hsing; Huang, San-Yuan

    2016-01-01

    Research on the effects of repeated opioid use on striatal dopamine transporters has yielded inconsistent results, possibly confounded by a history of methamphetamine or methadone exposure in opioid-dependent individuals. Previous studies have shown that striatal dopamine transporter density is positively correlated with the cognitive performance of healthy volunteers. This study aimed to investigate changes in striatal dopamine transporter density and their functional significance in opioid-dependent individuals. Single-photon emission computed tomography with [(99m) Tc]TRODAT-1 as a ligand was used to measure striatal dopamine transporter levels in 20 opioid-dependent individuals and 20 age- and sex-matched healthy controls. Opioid-dependent individuals had no history of methamphetamine or methadone use. The Wisconsin Card Sorting Test (WCST) was performed to assess neurocognitive function. We found that compared with healthy controls, opioid-dependent individuals showed a significant reduction in striatal dopamine transporter density. They also showed poorer performance on the WCST in terms of the trials administered, total errors, perseverative responses, perseverative errors, and non-perseverative errors. Striatal dopamine transporter levels negatively correlated with non-perseverative errors not only in opioid-dependent individuals but also in healthy controls. These findings suggest that in human, repeated opioid exposure reduces striatal dopamine transporter density, which can be associated with non-perseverative errors. Non-perseverative errors may be one of the more sensitive parameters in WCST to identify working memory deficits associated with striatal dopamine transporter reduction. Moreover, we suggest that whether opioid-associated neurotoxicity is reversible depends on the brain region. PMID:25439653

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

    PubMed

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

    2016-01-01

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

  4. 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

  5. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

    Dew, Brian J

    2010-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  10. 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

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

    PubMed

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

    2016-01-01

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

  12. Physical Victimization of Rural Methamphetamine and Cocaine Users

    PubMed Central

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

    2012-01-01

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

  13. 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

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

    PubMed

    Kuribara, H; Tadokoro, S

    1983-02-01

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

  15. Methamphetamine Use and Oral Health

    MedlinePlus

    FOR THE DENTAL PATIENT ... Methamphetamine use and oral health M ethamphetamine is an inexpensive, easy-to-make illicit drug. It is known by several street names: “meth,” “speed,” “ice,” “chalk,” “crank,” “fire,” “glass,” “crystal” and “tina.” It is ...

  16. 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

  17. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  18. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  19. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  20. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  1. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  2. Need for Methamphetamine Programming in Extension Education

    ERIC Educational Resources Information Center

    Beaudreault, Amy R.; Miller, Larry E.

    2011-01-01

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

  3. Methamphetamine Use: Hazards and Social Influences.

    ERIC Educational Resources Information Center

    Wermuth, Laurie

    2000-01-01

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

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

    PubMed Central

    Brecht, Mary-Lynn; Herbeck, Diane

    2015-01-01

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

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

    PubMed

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

    2004-01-01

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

  6. 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

  7. 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

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

    PubMed

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

    1996-10-01

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

  9. 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

  10. Working memory fMRI activation in cocaine-dependent subjects: association with treatment response.

    PubMed

    Moeller, F Gerard; Steinberg, Joel L; Schmitz, Joy M; Ma, Liangsuo; Liu, Shijing; Kjome, Kimberly L; Rathnayaka, Nuvan; Kramer, Larry A; Narayana, Ponnada A

    2010-03-30

    Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections. PMID:20153142

  11. Predicting Rapid Relapse Following Treatment for Chemical Dependence: A Matched-Subjects Design.

    ERIC Educational Resources Information Center

    Svanum, Soren; McAdoo, William George

    1989-01-01

    Persons who underwent residential treatment for chemical dependency were identified as three-month treatment failures (N=52) or successes (N=52). Subjects were matched on Minnesota Multiphasic Personality Inventory (MMPI) scores. Found posttreatment depression, anxiety, and sleep problems strongly related to failure among psychiatric MMPI group;…

  12. Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

    MedlinePlus

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

  13. Surgical Intervention for Penile Methamphetamine Injections

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-10-25

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

  15. Quality of life and health of opioid-dependent subjects in India

    PubMed Central

    Giri, Om Prakash; Srivastava, Mona; Shankar, Ravi

    2014-01-01

    Background and Objectives: The quality of life (QoL) of substance abusers is known to be severely impaired. This study was carried out to assess the impact of opioid dependence on the QoL of subjects and compared it with the normal subjects. Materials and Methods: Based on specified inclusion criteria a total of 47 subjects were recruited from a tertiary care center from India. The WHOQoL-BREF scale domain scores obtained at baseline were compared to that of normal subjects. An assessment of dysfunction and reasons for continuing and other parameters were assessed. Results: WHOQoL-BREF domains (Physical, Psychological, Social relationships and Environment) showed significantly lower scores and the difference was statistically significant. Interpretation and Conclusions: The results showed that QoL is an important parameter in assessment of substance abusers and can be used for long-term prognosis of these individuals. PMID:25288838

  16. Methamphetamine Vaccines: Improvement through Hapten Design.

    PubMed

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

    2016-04-28

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

  17. Psychosocial treatment for methamphetamine use disorders: a preliminary randomized controlled trial of cognitive behavior therapy and Acceptance and Commitment Therapy.

    PubMed

    Smout, Matthew F; Longo, Marie; Harrison, Sonia; Minniti, Rinaldo; Wickes, Wendy; White, Jason M

    2010-04-01

    Acceptance and Commitment Therapy (ACT) incorporates developments in behavior therapy, holds promise but has not been evaluated for methamphetamine use disorders. The objective of this study was to test whether ACT would increase treatment attendance and reduce methamphetamine use and related harms compared to cognitive behavior therapy (CBT). One hundred and four treatment-seeking adults with methamphetamine abuse or dependence were randomly assigned to receive 12 weekly 60-minute individual sessions of ACT or CBT. Attrition was 70% at 12 weeks and 86% at 24 weeks postentry. Per intention-to-treat analysis, there were no significant differences between the treatment groups in treatment attendance (median 3 sessions), and methamphetamine-related outcomes; however, methamphetamine use (toxicology-assessed and self-reported), negative consequences, and dependence severity significantly improved over time in both groups. Although ACT did not improve treatment outcomes or attendance compared to CBT, it may be a viable alternative to CBT for methamphetamine use disorders. Future rigorous research in this area seems warranted. PMID:20408061

  18. 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

  19. 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

  20. Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls

    PubMed Central

    Ma, Liangsuo; Steinberg, Joel L.; Cunningham, Kathryn A.; Lane, Scott D.; Bjork, James M.; Neelakantan, Harshini; Price, Amanda E.; Narayana, Ponnada A.; Kosten, Thomas R.; Bechara, Antoine; Moeller, F. Gerard

    2015-01-01

    Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated with response inhibition in CD subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The performance on the Go/NoGo task was not significantly different between CD subjects and controls. The DCM analysis revealed that prefrontal–striatal connectivity was modulated (influenced) during the NoGo conditions for both groups. The effective connectivity from left (L) anterior cingulate cortex (ACC) to L caudate was similarly modulated during the Easy NoGo condition for both groups. During the Hard NoGo condition in controls, the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to L caudate became more positive, and the effective connectivity from R ventrolateral prefrontal cortex (VLPFC) to L caudate became more negative. In CD subjects, the effective connectivity from L ACC to L caudate became more negative during the Hard NoGo conditions. These results indicate that during Hard NoGo trials in CD subjects, the ACC rather than DLPFC or VLPFC influenced caudate during response inhibition. PMID:26082893

  1. Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls.

    PubMed

    Ma, Liangsuo; Steinberg, Joel L; Cunningham, Kathryn A; Lane, Scott D; Bjork, James M; Neelakantan, Harshini; Price, Amanda E; Narayana, Ponnada A; Kosten, Thomas R; Bechara, Antoine; Moeller, F Gerard

    2015-01-01

    Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated with response inhibition in CD subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The performance on the Go/NoGo task was not significantly different between CD subjects and controls. The DCM analysis revealed that prefrontal-striatal connectivity was modulated (influenced) during the NoGo conditions for both groups. The effective connectivity from left (L) anterior cingulate cortex (ACC) to L caudate was similarly modulated during the Easy NoGo condition for both groups. During the Hard NoGo condition in controls, the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to L caudate became more positive, and the effective connectivity from R ventrolateral prefrontal cortex (VLPFC) to L caudate became more negative. In CD subjects, the effective connectivity from L ACC to L caudate became more negative during the Hard NoGo conditions. These results indicate that during Hard NoGo trials in CD subjects, the ACC rather than DLPFC or VLPFC influenced caudate during response inhibition. PMID:26082893

  2. METHAMPHETAMINE: HERE WE GO AGAIN?

    PubMed Central

    Maxwell, Jane Carlisle; Brecht, Mary-Lynn

    2011-01-01

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

  3. What You Need to Know about Drugs: Methamphetamines

    MedlinePlus

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

  4. 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.

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

    PubMed Central

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

    1972-01-01

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

  6. 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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2014-01-01

    Jumping to conclusions (JTC) during probabilistic reasoning is a cognitive bias repeatedly demonstrated in people with schizophrenia and shown to be associated with delusions. Little is known about the neurochemical basis of probabilistic reasoning. We tested the hypothesis that catecholamines influence data gathering and probabilistic reasoning by administering intravenous methamphetamine, which is known to cause synaptic release of the catecholamines noradrenaline and dopamine, to healthy humans whilst they undertook a probabilistic inference task. Our study used a randomised, double-blind, cross-over design. Seventeen healthy volunteers on three visits were administered either placebo or methamphetamine or methamphetamine preceded by amisulpride. In all three conditions participants performed the “beads” task in which participants decide how much information to gather before making a probabilistic inference, and which measures the cognitive bias towards jumping to conclusions. Psychotic symptoms triggered by methamphetamine were assessed using Comprehensive Assessment of At-Risk Mental States (CAARMS). Methamphetamine induced mild psychotic symptoms, but there was no effect of drug administration on the number of draws to decision (DTD) on the beads task. DTD was a stable trait that was highly correlated within subjects across visits (intra-class correlation coefficients of 0.86 and 0.91 on two versions of the task). The less information was sampled in the placebo condition, the more psychotic-like symptoms the person had after the methamphetamine plus amisulpride condition (p = 0.028). Our results suggest that information gathering during probabilistic reasoning is a stable trait, not easily modified by dopaminergic or noradrenergic modulation. PMID:25061949

  9. 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

  10. 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…

  11. Methamphetamine

    MedlinePlus

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

  12. Methamphetamine

    MedlinePlus

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

  13. Methamphetamine

    MedlinePlus

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

  14. Effects of Family-Centered Empowerment Model Based Education Program on Quality of Life in Methamphetamine Users and Their Families

    PubMed Central

    Ghasemi, Afsaneh; Rahimi Foroshani, Abbass; Kheibar, Nasrin; Latifi, Marziye; Khanjani, Narges; Eshagh Afkari, Mohammad; Taghdisi, Mohammad Hossein; Ghasemi, Faranak; Shojaeizadeh, Davoud; Dastoorpour, Maryam

    2014-01-01

    Background: Nowadays there are more concerns about drug treatment of methamphetamine abusers whereas quality of life (QOL) related supportive psychotherapy is less credited. Objectives: This study aimed to evaluate the effects of family-centered empowerment model on social support and QOL of methamphetamine users and their families. Patients and Methods: This study was a randomized clinical trial; individuals were randomly allocated to three groups: a group for educating methamphetamine users in recovery (95 subjects), a group for educating a family member of methamphetamine users in recovery (95 subjects) and a control group (95 subjects). Data collecting instruments were standard questionnaires of social support and health-related quality of life (HRQOL). Data were analyzed using χ2-test, t-test, paired t-test, Pearson’s correlation and ANOVA. Results: Mean scores of QOL and social support dimensions changed significantly in two intervention groups (P < 0.0001), but didn’t change in the control group (P > 0.05). Also, there was a positive significant relation (P < 0.05) between total social support and all dimensions of QOL for all study groups. Conclusions: Family-centered empowerment model, easily adapted to methamphetamine users and their families, leads to improved social supports and QOL. PMID:24829765

  15. 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

  16. A new survey of methamphetamine users in treatment: who they are, why they like "meth," and why they need additional services.

    PubMed

    Maxwell, Jane Carlisle

    2014-05-01

    The quality and quantity of illicit methamphetamine has recently increased due to introduction of a new precursor, 1-phenyl-2-propanone (P2P). This paper updates the problems associated with methamphetamine use. Methamphetamine-using clients (N = 222) entering a Texas program participated in computer-assisted interviews in 2010 and 2011 about routes of administration, other drugs used, severity of dependence, mental and physical health, perceived risks and benefits of use, family history, and abuse and neglect experienced as children and adults. Special needs of this population include therapies for trauma, gender-focused counseling, safe housing, and prevention messages to discourage use of the drug. PMID:24093526

  17. 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

  18. Secretory vesicle rebound hyperacidification and increased quantal size due to prolonged methamphetamine exposure

    PubMed Central

    Markov, Dmitriy; Mosharov, Eugene V.; Setlik, Wanda; Gershon, Michael D.; Sulzer, David

    2009-01-01

    Acute exposure to amphetamines collapses secretory vesicle pH gradients, which increases cytosolic catecholamine levels while decreases the quantal size of catecholamine release during fusion events. Amphetamine and methamphetamine, however, are retained in tissues over long durations. We used optical and electron microscopic probes to measure the effects of long-term methamphetamine exposure on secretory vesicle pH, and amperometry and intracellular patch electrochemistry to observe the effects on neurosecretion and cytosolic catecholamines in cultured rat chromaffin cells. In contrast to acute methamphetamine effects, exposure to the drug for 6–48 h at 10 μM and higher concentrations produced a concentration-dependent rebound hyperacidification of secretory vesicles. At 5–10 μM levels, methamphetamine increased the quantal size and reinstated exocytotic catecholamine release, although very high (>100 μM) levels of the drug, while continuing to produce rebound hyperacidification, did not increase quantal size. Secretory vesicle rebound hyperacidification was temperature dependent with optimal response at ~ 37°C, was not blocked by the transcription inhibitor, puromycin, and appears to be a general compensatory response to prolonged exposure with membranophilic weak bases, including amphetamines, methylphenidate, cocaine, and ammonia. Thus, under some conditions of prolonged exposure, amphetamines and other weak bases can enhance, rather than deplete, the vesicular release of catecholamines via a compensatory response resulting in vesicle acidification. PMID:19014382

  19. Neurophysiology of Hungarian subject-verb dependencies with varying intervening complexity.

    PubMed

    Jolsvai, Hajnal; Sussman, Elyse; Csuhaj, Roland; Csépe, Valéria

    2011-12-01

    Non-adjacent dependencies are thought to be more costly to process than sentences wherein dependents immediately follow or precede what they depend on. In English locality effects have been revealed, while in languages with rich case marking (German and Hindi) sentence final structures show anti-locality-effects. The motivation of the current study is to test whether locality effects can be directly applied to a typologically different language than those investigated so far. Hungarian is a "topic prominent" language; it permits a variation of possible word sequencing for semantic reasons, including SVO word order. Hungarian also has a rich morphological system (e.g., rich case system) and postpositions to indicate grammatical functions. In the present ERP study, Hungarian subject-verb dependencies were compared by manipulating the mismatch of number agreement between the sentence's initial noun phrase and the sentence's final intransitive verb as well as the complexity of the intervening sentence material, interrupting the dependencies. Possible lexical class and frequency or cloze-probability effects for the first two words of the intervening sentence material were revealed when used separate baseline for each word, while at the third word of the intervening material as well as at the main verb ERPs were not modulated by complexity but at the verb ERPs were enhanced by grammaticality. Ungrammatical sentences enlarged the amplitude of both LAN and P600 components at the main verb. These results are in line with studies suggesting that the retrieval of the first element of a dependency is not influenced by distance from the second element, as the first element is directly accessible when needed for integration (e.g., McElree, 2000). PMID:21740931

  20. Tracking Irregular Morphophonological Dependencies in Natural Language: Evidence from the Acquisition of Subject-Verb Agreement in French

    ERIC Educational Resources Information Center

    Nazzi, Thierry; Barriere, Isabelle; Goyet, Louise; Kresh, Sarah; Legendre, Geraldine

    2011-01-01

    This study examines French-learning infants' sensitivity to grammatical non-adjacent dependencies involving subject-verb agreement (e.g., "le/les garcons 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…

  1. A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Perez, Audrey Y.; Haney, Margaret; Foltin, Richard W.

    2015-01-01

    Rationale Despite their chemical similarities, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) produce differing neurochemical and behavioral responses in animals. In humans, individual studies of methamphetamine and MDMA indicate that the drugs engender overlapping and divergent effects; there are only limited data comparing the two drugs in the same individuals. Objectives This study examined the effects of methamphetamine and MDMA using a within-subject design. Methods Eleven adult volunteers completed this 13-day residential laboratory study, which consisted of four 3-day blocks of sessions. On the first day of each block, participants received oral methamphetamine (20, 40 mg), MDMA (100 mg), or placebo. Drug plasma concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and after. Food intake and sleep were also assessed. On subsequent days of each block, placebo was administered and residual effects were assessed. Results Acutely, both drugs increased cardiovascular measures and “positive” subjective effects and decreased food intake. In addition, when asked to identify each drug, participants had difficulty distinguishing between the amphetamines. The drugs also produced divergent effects: methamphetamine improved performance and disrupted sleep, while MDMA increased “negative” subjective-effect ratings. Few residual drug effects were noted for either drug. Conclusions It is possible that the differences observed could explain the differential public perception and abuse potential associated with these amphetamines. Alternatively, the route of administration by which the drugs are used recreationally might account for the many of the effects attributed to these drugs (i.e., MDMA is primarily used orally, whereas methamphetamine is used by routes associated with higher abuse potential). PMID:21713605

  2. Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate.

    PubMed

    Karpyak, V M; Biernacka, J M; Geske, J R; Jenkins, G D; Cunningham, J M; Rüegg, J; Kononenko, O; Leontovich, A A; Abulseoud, O A; Hall-Flavin, D K; Loukianova, L L; Schneekloth, T D; Skime, M K; Frank, J; Nöthen, M M; Rietschel, M; Kiefer, F; Mann, K F; Weinshilboum, R M; Frye, M A; Choi, D S

    2014-01-01

    Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow. PMID:25290263

  3. Extended access methamphetamine decreases immature neurons in the hippocampus which results from loss and altered development of neural progenitors without altered dynamics of the S-phase of the cell cycle

    PubMed Central

    Yuan, Clara J.; Quiocho, Jovy Marie D.; Kim, Airee; Wee, Sunmee; Mandyam, Chitra D.

    2011-01-01

    Methamphetamine addicts demonstrate impaired hippocampal-dependent cognitive function that could result from methamphetamine-induced maladaptive plasticity in the hippocampus. Reduced adult hippocampal neurogenesis observed in a rodent model of compulsive methamphetamine self-administration partially contributes to the maladaptive plasticity in the hippocampus. The potential mechanisms underlying methamphetamine-induced inhibition of hippocampal neurogenesis were identified in the present study. Key aspects of the cell cycle dynamics of hippocampal progenitors, including proliferation and neuronal development, were studied in rats that intravenously self-administered methamphetamine in a limited access (1 h/day: short access (ShA)-4 days and ShA-13 days) or extended access (6 h/day: long access (LgA)-4 days and LgA-13 days) paradigm. Immunohistochemical analysis of Ki-67 cells with 5-chloro-2’-deoxyuridine (CldU) demonstrated that LgA methamphetamine inhibited hippocampal proliferation by decreasing the proliferating pool of progenitors that are in the synthesis (S)-phase of the cell cycle. Double S-phase labeling with CldU and 5-iodo-2’-deoxyuridine (IdU) revealed that reduced S-phase cells were not due to alterations in the length of the S-phase. Further systematic analysis of Ki-67 cells with GFAP, Sox2, and DCX revealed that LgA methamphetamine-induced inhibition of hippocampal neurogenesis was attributable to impairment in the development of neuronal progenitors from preneuronal progenitors to immature neurons. Methamphetamine concomitantly increased hippocampal apoptosis, changes that were evident during the earlier days of self-administration. These findings demonstrate that methamphetamine self-administration initiates allostatic changes in adult neuroplasticity maintained by the hippocampus, including increased apoptosis, and altered dynamics of hippocampal neural progenitors. These data suggest that altered hippocampal plasticity by methamphetamine

  4. Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

    PubMed

    Sigal, R J; Purdon, C; Fisher, S J; Halter, J B; Vranic, M; Marliss, E B

    1994-10-01

    Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is

  5. 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

  6. Methamphetamine Exposure: A Rural Early Intervention Challenge

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  7. 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

  8. 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

  9. Glycemic control and nerve conduction abnormalities in non-insulin-dependent diabetic subjects.

    PubMed

    Graf, R J; Halter, J B; Pfeifer, M A; Halar, E; Brozovich, F; Porte, D

    1981-03-01

    The influence of therapy of hyperglycemia on the progression of diabetic neuropathy is unclear. We studied variables of glycemia and motor and sensory nerve conduction velocity in a group of 18 non-insulin-dependent diabetic subjects before and after institution of diabetes therapy. Diabetes therapy significantly reduced variables of glycemia after 1, 3, 6, and 12 months. Conduction velocity of the median motor nerve was improved from baseline at each time tested during treatment. In addition, peroneal and tibial motor nerve conduction velocities improved in patients whose levels of hyperglycemia were lowered. Moreover, extent of improvement of conduction velocity of some motor nerves was related to the degree of reduction of hyperglycemia. Sensory nerve conduction velocity was not altered by diabetes therapy. These findings support the hypothesis of a metabolic component to diabetic neuropathy and suggest that optimal glycemic control may be beneficial to patients with this disorder. PMID:7013592

  10. 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

  11. Anti-saccade error rates as a measure of attentional bias in cocaine dependent subjects.

    PubMed

    Dias, Nadeeka R; Schmitz, Joy M; Rathnayaka, Nuvan; Red, Stuart D; Sereno, Anne B; Moeller, F Gerard; Lane, Scott D

    2015-10-01

    Cocaine-dependent (CD) subjects show attentional bias toward cocaine-related cues, and this form of cue-reactivity may be predictive of craving and relapse. Attentional bias has previously been assessed by models that present drug-relevant stimuli and measure physiological and behavioral reactivity (often reaction time). Studies of several CNS diseases outside of substance use disorders consistently report anti-saccade deficits, suggesting a compromise in the interplay between higher-order cortical processes in voluntary eye control (i.e., anti-saccades) and reflexive saccades driven more by involuntary midbrain perceptual input (i.e., pro-saccades). Here, we describe a novel attentional-bias task developed by using measurements of saccadic eye movements in the presence of cocaine-specific stimuli, combining previously unique research domains to capitalize on their respective experimental and conceptual strengths. CD subjects (N = 46) and healthy controls (N = 41) were tested on blocks of pro-saccade and anti-saccade trials featuring cocaine and neutral stimuli (pictures). Analyses of eye-movement data indicated (1) greater overall anti-saccade errors in the CD group; (2) greater attentional bias in CD subjects as measured by anti-saccade errors to cocaine-specific (relative to neutral) stimuli; and (3) no differences in pro-saccade error rates. Attentional bias was correlated with scores on the obsessive-compulsive cocaine scale. The results demonstrate increased saliency and differential attentional to cocaine cues by the CD group. The assay provides a sensitive index of saccadic (visual inhibitory) control, a specific index of attentional bias to drug-relevant cues, and preliminary insight into the visual circuitry that may contribute to drug-specific cue reactivity. PMID:26164486

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

    PubMed

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

    2014-10-01

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

  13. 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.

  14. 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

  15. Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.

    PubMed

    Lane, Scott D; Green, Charles E; Schmitz, Joy M; Rathnayaka, Nuvan; Fang, Wendy B; Ferré, Sergi; Moeller, F Gerard

    2014-01-01

    Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS 'elated' scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3-4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous preclinical and

  16. Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine

    PubMed Central

    Lane, Scott D; Green, Charles E; Schmitz, Joy M; Rathnayaka, Nuvan; Fang, Wendy B; Ferré, Sergi; Moeller, F Gerard

    2014-01-01

    Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS ‘elated’ scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3–4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Lindsay, Brianna; Albrecht, Jennifer; Terplan, Mishka

    2011-01-01

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

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

    PubMed

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

    2016-08-01

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

  20. 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

  1. Nature of Functional Links in Valuation Networks Differentiates Impulsive Behaviors between Abstinent Heroin-Dependent Subjects and Nondrug-Using Subjects

    PubMed Central

    Zhai, Tianye; Shao, Yongcong; Chen, Gang; Ye, Enmao; Ma, Lin; Wang, Lubin; Lei, Yu; Chen, Guangyu; Li, Wenjun; Zou, Feng; Jin, Xiao; Li, Shi-Jiang; Yang, Zheng

    2015-01-01

    Advanced neuroimaging studies have identified brain correlates of pathological impulsivity in a variety of neuropsychiatric disorders. However, whether and how these spatially separate and functionally integrated neural correlates collectively contribute to aberrant impulsive behaviors remains unclear. Building on recent progress in neuroeconomics towards determining a biological account of human behaviors, we employed resting-state functional MRI to characterize the nature of the links between these neural correlates and to investigate their impact on impulsivity. We demonstrated that through functional connectivity with the ventral medial prefrontal cortex, the δ-network (regions of the executive control system, such as the dorsolateral prefrontal cortex) and the β-network (regions of the reward system involved in the mesocorticolimbic pathway), jointly influence impulsivity measured by the Barratt Impulsiveness Scale scores. In control nondrug-using subjects, the functional link between the β- and δ-networks is balanced, and the δ-network competitively controls impulsivity. However, in abstinent heroin-dependent subjects, the link is imbalanced, with stronger β-network connectivity and weaker δ-network connectivity. The imbalanced link is associated with impulsivity, indicating that the β- and δ-networks may mutually reinforce each other in abstinent heroin-dependent subjects. These findings of an aberrant link between the β- and δ-networks in abstinent heroin-dependent subjects may shed light on the mechanism of aberrant behaviors of drug addiction and may serve as an endophenotype to mark individual subjects’ self-control capacity. PMID:25944613

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

    PubMed

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

    2009-04-01

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

  3. 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.

  4. Theories of Addiction: Methamphetamine Users’ Explanations for Continuing Drug Use and Relapse

    PubMed Central

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

    2012-01-01

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

  5. Neurologic manifestations of chronic methamphetamine abuse

    PubMed Central

    Rusyniak, Daniel E.

    2011-01-01

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

  6. METHAMPHETAMINE: WHERE WILL THE STAMPEDE TAKE US?

    PubMed

    Sullivan, Danny; McDonough Michael

    2015-09-01

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

  7. Glycyrrhizae Radix Methanol Extract Attenuates Methamphetamine-Induced Locomotor Sensitization and Conditioned Place Preference

    PubMed Central

    Zhao, ZhengLin; Zhang, Jie; Jung, Ji Yun; Chang, Suchan; Zhou, FuBo; Zhao, JunChang; Lee, Bong Hyeo; Yang, Chae Ha; Zhao, RongJie

    2014-01-01

    Glycyrrhizae Radix modulates the neurochemical and locomotor alterations induced by acute psychostimulants in rodents via GABAb receptors. This study investigated the influence of methanol extract from Glycyrrhizae Radix (MEGR) on repeated methamphetamine- (METH-) induced locomotor sensitization and conditioned place preference (CPP). A cohort of rats was treated with METH (1 mg/kg/day) for 6 consecutive days, subjected to 6 days of withdrawal, and then challenged with the same dose of METH to induce locomotor sensitization; during the withdrawal period, the rats were administered MEGR (60 or 180 mg/kg/day). A separate cohort of rats was treated with either METH or saline every other day for 6 days in METH-paired or saline-paired chambers, respectively, to induce CPP. These rats were also administered MEGR (180 mg/kg) prior to every METH or CPP expression test. Pretreatment with MEGR (60 and 180 mg/kg/day) attenuated the expression of METH-induced locomotor sensitization dose-dependently, and 180 mg/kg MEGR significantly inhibited the development and expression of METH-induced CPP. Furthermore, administration of a selective GABAb receptor antagonist (SCH50911) prior to MEGR treatment effectively blocked the inhibitory effects of MEGR on locomotor sensitization, but not CPP. These results suggest that Glycyrrhizae Radix blocked repeated METH-induced behavioral changes via GABAb receptors. PMID:25386216

  8. 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

  9. 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

  10. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

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

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

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

    PubMed

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

    2015-04-01

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

  17. 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

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

    PubMed

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

    2011-01-01

    While many studies have examined correlates of trading sex for money, few have examined factors associated with exclusive trading of sex for drugs. We identified sociodemographic, behavioral, and psychological correlates of trading sex for methamphetamine in a sample of HIV-negative heterosexual men and women who were enrolled in a sexual risk reduction intervention in San Diego, California. Of 342 participants, 26% overall (21% of males and 31% of females) reported trading sex for methamphetamine in the past two months. Multiple logistic regression analysis revealed that recently trading sex for methamphetamine was independently associated with being female, homeless, binging on methamphetamine, sexual victimization in the past two months, engaging in anal sex 24 or more times in the past two months, and higher sexual compulsivity scores. Effective interventions for this high-risk population should consider gender-focused counseling for sexual abuse, motivational enhancement therapy, social-cognitive skills training, as well as enhanced access and utilization of social services, including drug treatment. PMID:21858954

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

    PubMed

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

    2016-05-01

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

  20. 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

    2016-01-01

    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

  1. Association of Smoking with Mu- Opioid Receptor Availability Before and During Naltrexone Blockade in Alcohol-Dependent Subjects

    PubMed Central

    Weerts, Elise M.; Wand, Gary S.; Kuwabara, Hiroto; Xu, Xiaoqiang; Frost, J.James; Wong, Dean F.; McCaul, Mary E.

    2012-01-01

    Persons with a history of alcohol dependence are more likely to use tobacco and to meet criteria for nicotine dependence compared to social drinkers or nondrinkers. The high levels of comorbidity of nicotine and alcohol use and dependence are thought to be related to interactions between nicotinic, opioid and dopamine receptors in mesolimbic regions. The current study examined whether individual differences in regional mu-opioid receptor (MOR) availability were associated with tobacco use, nicotine dependence, and level of nicotine craving in 25 alcohol dependent (AD) subjects. AD subjects completed an inpatient protocol, which included medically supervised alcohol withdrawal, monitored alcohol abstinence, transdermal nicotine maintenance (21 mg/day), and Positron Emission Tomography (PET) imaging using the MOR agonist [11C]-carfentanil (CFN) before (basal scan) and during treatment with 50 mg/day naltrexone (naltrexone scan). Subjects who had higher scores on the Fagerström Nicotine Dependence Test had significantly lower basal scan binding potential (BPND) across mesolimbic regions including the amygdala, cingulate, globus pallidus, thalamus and insula. Likewise, the number of cigarettes per day was negatively associated with basal scan BPND in mesolimbic regions Higher nicotine craving was significantly associated with lower BPND in amygdala, globus pallidus, putamen, thalamus and ventral striatum. Although blunted during naltrexone treatment, the negative association was maintained for nicotine dependence and cigarettes per day, but not for nicotine craving. These findings suggest that intensity of cigarette smoking and severity of nicotine dependence symptoms are systematically related to reduced BPND across multiple brain regions in AD subjects. PMID:23252742

  2. Event-Level Relationship between Methamphetamine Use Significantly Associated with Non-adherence to Pharmacologic Trial Medications in Event-Level Analyses

    PubMed Central

    Santos, Glenn-Milo; Vittinghoff, Eric; Santos, Deirdre; Colfax, Grant; Coffin, Phillip

    2014-01-01

    Background Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. Methods We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. Results We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49–0.98). In addition, age (AOR: 1.07; 95% CI: 1.02–1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64–0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. Conclusions Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles. PMID:25156227

  3. Neural Mechanisms Underlying Contextual Dependency of Subjective Values: Converging Evidence from Monkeys and Humans

    PubMed Central

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

    2015-01-01

    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. PMID:25653384

  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

    2015-02-01

    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. PMID:25653384

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

    PubMed

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

    2016-01-01

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

  6. 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

  7. 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. PMID:27161925

  8. 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.

  9. Differential regional effects of methamphetamine on dopamine transport.

    PubMed

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

    2008-08-20

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

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

    PubMed

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

    2016-07-15

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

  11. An ordinary mixed meal transiently impairs endothelium-dependent vasodilation in healthy subjects.

    PubMed

    Sarabi, M; Fugmann, A; Karlström, B; Berne, C; Lithell, H; Lind, L

    2001-06-01

    This study was designed to evaluate the effects of an ordinary mixed meal on endothelium-dependent vasodilation. Ten young healthy volunteers were given a mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was fat). In the fasting state, at 60 and 120 min after the start of the meal, endothelium-dependent vasodilation and endothelium-independent vasodilation were evaluated by local infusion of metacholine (4 microg min (-1)) and sodium nitroprusside (10 microg min (-1)) in the brachial artery. Blood flow in the forearm was measured using venous occlusion plethysmography. Endothelium-dependent vasodilation decreased from 15.4 +/- 3.3 (mean +/- SD) at fasting to 13.7 +/- 3.5 mL min (-1) (100 mL tissue)-1 (P < 0.01) 60 min after feeding, but had returned to the fasting level at 120 min. At 60 min, but not in the fasting state, the serum level of free fatty acids was inversely related to endothelium-dependent vasodilation (r=-0.74, P < 0.05), although no significant net changes in FFA levels were seen. Endothelium-independent vasodilation was not affected by the mixed meal. No similar attenuations in endothelium-dependent vasodilation were seen during control meals. In conclusion, an ordinary mixed meal transiently attenuated endothelium-dependent vasodilation. Free fatty acids may be involved in this effect on endothelial function. PMID:11442450

  12. 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.

  13. 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

  14. Glutamatergic Neurometabolites during Early Abstinence from Chronic Methamphetamine Abuse

    PubMed Central

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

    2015-01-01

    Background: The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon. Methods: We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a methamphetamine group of 44 adults who had chronically abused methamphetamine and a control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the methamphetamine group were studied as inpatients during the first week of abstinence from the drug and were not receiving treatment. Results: In the methamphetamine group, small but significant (5–15%, P<.05) decrements (vs control) in glutamate+glutamine were observed in posterior cingulate, precuneus, and right inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (P<.05) with years of methamphetamine abuse. The Beck Depression Inventory score was negatively correlated (P<.005) with glutamate+glutamine in right inferior frontal cortex. Conclusions: Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery. PMID:25522400

  15. Patient Reactance Moderates the Effect of Directive Telephone Counseling for Methamphetamine Users

    PubMed Central

    Karno, Mitchell; Farabee, David; Brecht, Mary-Lynn; Rawson, Richard

    2012-01-01

    Objective: This study examined the impact of the interaction between patient reactance and treatment directiveness on the effectiveness of telephone aftercare for methamphetamine dependence. Method: Reactance was assessed at baseline, and participants were randomly assigned to directive or nondirective treatment conditions. Logistic regression tested for the significance of the interaction as a predictor of 3-month and 12-month use of methamphetamine and stimulants. Results: A significant interaction was observed at the 3-month follow-up, in which the directive condition was less effective for patients higher in reactance and was more effective for patients lower in reactance. Among patients at a high level of reactance, the nondirective condition increased the likelihood of abstinence. Conclusions: This study suggests that, in the context of telephone-based care, directive interventions offer short-term clinical benefit for methamphetamine users who readily accept influence from authority figures, whereas nondirective interventions offer benefit for patients who do not readily accept influence. The short-term nature of these effects indicates that there is a need for brief but ongoing telephone support to maintain treatment gains. PMID:22846250

  16. Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

    PubMed

    Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

    1995-05-01

    A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects. PMID:7587920

  17. 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

  18. Neuropsychological function in older subjects with non-insulin-dependent diabetes mellitus.

    PubMed

    Atiea, J A; Moses, J L; Sinclair, A J

    1995-08-01

    Neuropsychological function was compared in three well-matched groups of subjects: Group 1, 20 diabetic patients with hypertension, mean age 69.1 +/- 4.8 years, 14 males and 6 females; Group 2, 20 normotensive diabetic patients, mean age 69.0 +/- 6.2 years, 14 males and 6 females; Group 3, 20 healthy community controls, mean age 68.1 +/- 4.5 years, 13 males and 7 females. There were no significant differences between the groups in education or estimated IQ using the NART (National Adult Reading Test). Groups 1 and 2 did not differ significantly in duration of diabetes (mean 10.6 and 9.5 years, respectively), or mean glycosylated haemoglobin, HbA1 (mean 9.8 and 10.6%, respectively), or mean blood glucose before and after testing. On a battery neuropsychological tests, sensitive to cognitive impairment in older subjects, analysis of covariance using estimated IQ as the covariate showed no significant differences between the groups on tests of recall, with (Brown-Peterson Test) and without (Kendrick Object Learning Test) interference, forward and backward digit span, concentration (serial subtraction), verbal fluency, immediate and delayed prose recall, digit symbol substitution or psychomotor speed (Kendrick Digit Copying Test). These results provide no support for an association between cognitive deficits and Type 2 diabetes mellitus in older subjects or for the view that such deficits may also be mediated by hypertension. PMID:7587006

  19. Effect of Abstinence on Depression, Anxiety, and Quality of Life in Chronic Methamphetamine Users in a Therapeutic Community

    PubMed Central

    Bagheri, Maryam; Mokri, Azarakhsh; Khosravi, Aliakbar; Kabir, Kourosh

    2015-01-01

    Background: During withdrawal, patients experience different symptoms. These symptoms are associated with relapse. Understanding different outcomes of methamphetamine abstinence is useful for finding better treatments for dependence. Objectives: This study aimed to show the effects of abstinence on depression, anxiety, and quality of life in methamphetamine users. Patients and Methods: A prospective quasi-experimental (before and after study) method was used to show the effect of 3 weeks abstinence on depression, anxiety, and quality of life. A convenient sample of addicted people entered into the study and 34 people completed the study. Beck Depression Scale, Cattell Anxiety Inventory and Short Form Health Survey (SF-36) (for assessing quality of life), were used for outcome assessments. Results: The mean depression score after abstinence decreased significantly (P < 0.001). Both hidden and obvious anxiety and total anxiety had a high level at admission and after 3 weeks of abstinence, the mean level of anxiety did not change significantly (P < 0.096). However, the quality of life increased after 3 weeks of abstinence (P < 0.001). Conclusions: Depression and anxiety are prevalent in methamphetamine users. Short-term abstinence improves depression and quality of life but does not improve anxiety in methamphetamine abusers. During follow up of these patients, addressing depression and anxiety is important to achieve better results. PMID:26495258

  20. 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. PMID:26503310

  1. Neurologic Manifestations of Chronic Methamphetamine Abuse

    PubMed Central

    Rusyniak, Daniel E.

    2013-01-01

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

  2. Arterial Pressure Variation as a Biomarker of Preload Dependency in Spontaneously Breathing Subjects – A Proof of Principle

    PubMed Central

    Bronzwaer, Anne-Sophie G. T.; Ouweneel, Dagmar M.; Stok, Wim J.; Westerhof, Berend E.; van Lieshout, Johannes J.

    2015-01-01

    Objective Pulse (PPV) and systolic pressure variation (SPV) quantify variations in arterial pressure related to heart-lung interactions and have been introduced as biomarkers of preload dependency to guide fluid treatment in mechanically ventilated patients. However, respiratory intra-thoracic pressure changes during spontaneous breathing are considered too small to affect preload and stroke volume sufficiently for the detection by PPV and/or SPV. This study addressed the effects of paced breathing and/or an external respiratory resistance on PPV and SPV in detecting preload dependency in spontaneously breathing subjects. Methods In 10 healthy subjects, hemodynamic and respiratory parameters were evaluated during progressive central hypovolemia (head-up tilt). Breathing conditions were varied by manipulating breathing frequency and respiratory resistance. Subjects responding with a reduction in stroke volume index ≥15% were classified as having developed preload dependency. The ability for PPV and SPV to predict preload dependency was expressed by the area under the ROC curve (AUC). Results A breathing frequency at 6/min increased the PPV (16±5% vs. 10±3%, p<0.001) and SPV (9±3% vs. 5±2%, p<0.001) which was further enhanced by an expiratory resistance (PPV: 19±3%, p = 0.025 and SPV: 10±2%, p = 0.047). These respiratory modifications, compared to free breathing, enhanced the predictive value of PPV with higher accuracy (AUC: 0.92 vs. 0.46). Conclusion Under conditions of progressive central hypovolemia, the application of an external respiratory resistance at a breathing frequency of 6/min enhanced PPV and SPV and is worth further study for detection of preload dependency from arterial pressure variations in non-ventilated subjects. PMID:26335939

  3. 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

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

    PubMed

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

    2016-09-01

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

  5. Computational microstructure modeling of asphalt mixtures subjected to rate-dependent fracture

    NASA Astrophysics Data System (ADS)

    Aragao, Francisco Thiago Sacramento

    2011-12-01

    Computational microstructure models have been actively pursued by the pavement mechanics community as a promising and advantageous alternative to limited analytical and semi-empirical modeling approaches. The primary goal of this research is to develop a computational microstructure modeling framework that will eventually allow researchers and practitioners of the pavement mechanics community to evaluate the effects of constituents and mix design characteristics (some of the key factors directly affecting the quality of the pavement structures) on the mechanical responses of asphalt mixtures. To that end, the mixtures are modeled as heterogeneous materials with inelastic mechanical behavior. To account for the complex geometric characteristics of the heterogeneous mixtures, an image treatment process is used to generate finite element meshes that closely reproduce the geometric characteristics of aggregate particles (size, shape, and volume fraction) that are distributed within a fine aggregate asphaltic matrix (FAM). These two mixture components, i.e., aggregate particles and FAM, are modeled, respectively, as isotropic linear elastic and isotropic linear viscoelastic materials and the material properties required as inputs for the computational model are obtained from simple and expedited laboratory tests. In addition to the consideration of the complex geometric characteristics and inelastic behavior of the mixtures, this study uses the cohesive zone model to simulate fracture as a gradual and rate-dependent phenomenon in which the initiation and propagation of discrete cracks take place in different locations of the mixture microstructure. Rate-dependent cohesive zone fracture properties are obtained using a procedure that combines laboratory tests of semi-circular bending specimens of the FAM and their numerical simulations. To address the rate-dependent fracture characteristics of the FAM phase, a rate-dependent cohesive zone model is developed and

  6. 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

  7. D-(U-11C)glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    SciTech Connect

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V. )

    1990-05-01

    We used D-(U-11C)glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-(U-11C)-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia (arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects). Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects.

  8. Groundwater flow within a sub-aerial orogenic wedge subject to depth-dependent permeability structure

    NASA Astrophysics Data System (ADS)

    Pollyea, R.; Van Dusen, E.; Fischer, M. P.

    2014-12-01

    In recent years, investigators have revisited the problem of basin-scale fluid flow with an emphasis on depth-dependent permeability, which is a frequently observed geological phenomenon that is seldom accounted for in basin-scale flow models. These recent investigations have shown that depth-dependent permeability at the basin scale strongly influences the relationship between sub-basin and regional-scale flow paths. Here, we revisit topography driven fluid flow within a foreland basin using a numerical modeling experiment designed to assess first-order fluid system behavior when permeability decreases systematically with depth. Critical taper theory is invoked to define two-dimensional basin geometry, and three sub-aerially exposed orogenic wedge models are presented with critical taper angles of 2°, 4°, and 10°. To assess the combined influence of topographic slope and depth-dependent permeability, a constant rate infiltration is applied at the wedge surface and a transient simulation is performed within each model for 500,000 years. Our results suggest that fluid system structure within the narrowly tapering orogenic wedge (2°) is explained by recent investigations applying depth-decaying permeability to the classic Tóth basin; however, increasing topographic slope beyond 3° results in a fundamentally different fluid system architecture. As topographic slope increases, fluid system structure is characterized by (1) dominant regional flow paths and little, if any, sub-basin scale fluid circulation, (2) shallow meteoric water penetration, (3) a stratified distribution of groundwater residence time without pronounced stagnation points. Moreover, for a given detachment slope, these effects become more pronounced as topographic gradient increases.

  9. Redox-dependent regulation, redox control and oxidative damage in plant cells subjected to abiotic stress.

    PubMed

    Dietz, Karl-Josef

    2010-01-01

    Stress development intricately involves uncontrolled redox reactions and oxidative damage to functional macromolecules. Three phases characterize progressing abiotic stress and the stress strength; in the first phase redox-dependent deregulation in metabolism, in the second phase detectable development of oxidative damage and in the third phase cell death. Each phase is characterized by traceable biochemical features and specific molecular responses that reflect on the one hand cell damage but on the other hand indicate specific regulation and redox signalling aiming at compensation of stress impact. PMID:20387040

  10. Turgidity-dependent petiole flexibility enables efficient water use by a tree subjected to water stress.

    PubMed

    Gonzalez-Rodriguez, David; Cournède, Paul-Henry; de Langre, Emmanuel

    2016-06-01

    Water stress is a major cause of tree mortality. In response to drought, leaves wilt due to an increase in petiole flexibility. We present an analytical model coupling petiole mechanics, thermal balance, and xylem hydraulics to investigate the role of petiole flexibility in protecting a tree from water stress. Our model suggests that turgidity-dependent petiole flexibility can significantly attenuate the minimal xylem pressure and thus reduce the risk of cavitation. Moreover, we show that petiole flexibility increases water use efficiency by trees under water stress. PMID:26992577

  11. 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.

  12. Non-linear dielectric signatures of entropy changes in liquids subject to time dependent electric fields

    NASA Astrophysics Data System (ADS)

    Richert, Ranko

    2016-03-01

    A model of non-linear dielectric polarization is studied in which the field induced entropy change is the source of polarization dependent retardation time constants. Numerical solutions for the susceptibilities of the system are obtained for parameters that represent the dynamic and thermodynamic behavior of glycerol. The calculations for high amplitude sinusoidal fields show a significant enhancement of the steady state loss for frequencies below that of the low field loss peak. Also at relatively low frequencies, the third harmonic susceptibility spectrum shows a "hump," i.e., a maximum, with an amplitude that increases with decreasing temperature. Both of these non-linear effects are consistent with experimental evidence. While such features have been used to conclude on a temperature dependent number of dynamically correlated particles, Ncorr, the present result demonstrates that the third harmonic susceptibility display a peak with an amplitude that tracks the variation of the activation energy in a model that does not involve dynamical correlations or spatial scales.

  13. The relationship between methamphetamine and popper use and risk of HIV seroconversion in the multicenter AIDS cohort study

    PubMed Central

    Plankey, Michael W.; Ostrow, David G.; Stall, Ron; Cox, Christopher; Li, Xiuhong; Peck, James A.; Jacobson, Lisa P.

    2012-01-01

    Background The association between methamphetamine use and HIV seroconversion for men who have sex with men (MSM) was examined using longitudinal data from the Multicenter AIDS Cohort Study. Methods Seronegative (n=4003) men enrolled in 1984–85, 1987–1991 and 2001–2003 were identified. Recent methamphetamine and popper use were determined at either the current or the previous visit. Time to HIV-seroconversion was the outcome of interest. Covariates included race/ethnicity, cohort, study site, educational level, number of sexual partners, number of unprotected insertive anal sexual partners (UIAS), number of unprotected receptive anal sexual partners (URAS), insertive rimming, cocaine use at either the current or last visit, ecstasy use at either the current or last visit, any needle use since last visit, CES-D depression score > 16 since last visit, and alcohol consumption. Results After adjusting for covariates, there was an approximately 1.46-fold independent increased relative hazard (HR) of HIV seroconversion for methamphetamine use. The HR associated with popper use was 2.1 [95% CI 1.63, 2.70]. The HR of HIV seroconversion increased with URAS ranging from 1.87 [95% CI 1.40, 2.51] for 1 partner to 9.32 [95% CI 6.20, 13.98] for 5+ partners. The joint HR for methamphetamine and popper use was 3.05 [95% CI 2.12, 4.37]. Most notably, there was a significant joint HR for methamphetamine use and URAS of 2.71 [95% CI 1.81, 4.04] for men with 1 unprotected receptive anal sex partner, which increased in a dose-dependent manner for >1 partners. Conclusions Further examination of the synergism of patterns of drug use and sexual risk behaviors on rates of HIV seroconversion will be necessary in order to develop new HIV prevention strategies for drug-using MSM. PMID:17325605

  14. Acute Iodine Toxicity From a Suspected Oral Methamphetamine Ingestion

    PubMed Central

    Bulloch, Marilyn N

    2014-01-01

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

  15. 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.

  16. Are inmates’ subjective sleep problems associated with borderline personality, psychopathy, and antisocial personality independent of depression and substance dependence?

    PubMed Central

    Harty, Laura; Duckworth, Rebecca; Thompson, Aaron; Stuewig, Jeffrey; Tangney, June P.

    2009-01-01

    Previous research investigating the relationship between Borderline Personality Disorder (BPD) and sleep problems, independent of depression, has been conducted on small atypical samples with mixed results. This study extends the literature by utilizing a much larger sample and by statistically controlling for depression and substance dependence. Subjective reports of sleep problems were obtained from 513 jail inmates (70% male) incarcerated on felony charges. Symptoms of BPD were significantly associated with sleep problems even when controlling for depression. Thus, sleep problems associated with BPD cannot be attributed simply to co-morbid symptoms of depression and substance dependence was ruled out as proximal causes for this relationship. Symptoms of depression, but not Antisocial Personality features, were related to sleep problems independent of substance dependence. Treatment of individuals with BPD may be more effective if sleep problems are explicitly addressed in the treatment plan. PMID:20198127

  17. 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.

  18. METHAMPHETAMINE TOXICITY AND MESSENGERS OF DEATH

    PubMed Central

    Krasnova, Irina N.; Cadet, Jean Lud

    2009-01-01

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

  19. Melatonin Attenuates Methamphetamine-Induced Neurotoxicity.

    PubMed

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2016-01-01

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

  20. 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

  1. Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

    PubMed Central

    2013-01-01

    Background The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence. Methods We evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11–12 month-old) rats. Results We did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry. Conclusions With a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of

  2. Modeling subject-specific phase-dependent effects and variations in longitudinal responses via a geometric Brownian motion process.

    PubMed

    Zhu, Li; Hsieh, Fushing; Li, Juan; Chi, Eric

    2011-08-30

    We address statistical issues regarding modeling a collection of longitudinal response trajectories characterized by the presence of subject-specific phase-dependent effects and variation. To accommodate these two time-varying individual characteristics, we employ a geometric stochastic differential equation for modeling based on a Brownian motion process and develop a two-step paradigm for statistical analysis. This paradigm reverses the order of statistical inference in random effects model. We first extract individual information about phase-dependent treatment effects and volatility parameters for all subjects. Then, we derive the association relationship between the parameters characterizing the individual longitudinal trajectories and the corresponding covariates by means of multiple regression analysis. The stochastic differential equation model and the two-step paradigm together provide significant advantages both in modeling flexibility and in computational efficiency. The modeling flexibility is due to the easy adaptation of temporal change points for subject-specific phase transition in treatment effects, whereas the computational efficiency benefits in part from the independent increment property of Brownian motion that avoids high-dimensional integration. We demonstrate our modeling approach and statistical analysis on a real data set of longitudinal measurements of disease activity scores from a rheumatoid arthritis study. PMID:21751228

  3. Ghrelin system in alcohol-dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving

    PubMed Central

    Leggio, Lorenzo; Ferrulli, Anna; Cardone, Silvia; Nesci, Antonio; Miceli, Antonio; Malandrino, Noemi; Capristo, Esmeralda; Canestrelli, Benedetta; Monteleone, Palmiero; Kenna, George A.; Swift, Robert M.; Addolorato, Giovanni

    2016-01-01

    Animal studies suggest that the gut-brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics. This investigation consisted of two studies. Study 1 was a 12-week study with alcohol-dependent subjects, where plasma ghrelin determinations were assessed four times (T0-T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone (GH) levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case-control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol-dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non-abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol-dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant. This investigation suggests that ghrelin is potentially able to affect alcohol-seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD. PMID:21392177

  4. 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

  5. Decreased frontal lobe phosphocreatine levels in methamphetamine users

    PubMed Central

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

    2012-01-01

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

  6. On the Josephson effect in a Bose-Einstein condensate subject to a density-dependent gauge potential

    NASA Astrophysics Data System (ADS)

    Edmonds, M. J.; Valiente, M.; Öhberg, P.

    2013-07-01

    We investigate the coherent dynamics of a Bose-Einstein condensate in a double well, subject to a density-dependent gauge potential. Further, we derive the nonlinear Josephson equations that allow us to understand the many-body system in terms of a classical Hamiltonian that describes the motion of a nonrigid pendulum with an initial angular offset. Finally we analyse the phase-space trajectories of the system, and describe how the self-trapping is affected by the presence of an interacting gauge potential.

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

    ERIC Educational Resources Information Center

    Connell-Carrick, Kelli

    2007-01-01

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

  8. 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…

  9. 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.…

  10. 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

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

    PubMed

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

    2013-10-01

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

  12. 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

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

    PubMed

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

    2014-07-01

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

  15. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Musshoff, F

    2000-02-01

    The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources. PMID:10711406

  18. The Methamphetamine Problem in the United States

    PubMed Central

    Gonzales, Rachel; Mooney, Larissa; Rawson, Richard

    2015-01-01

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

  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. Role for Rab10 in Methamphetamine-Induced Behavior

    PubMed Central

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

    2015-01-01

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

  1. Association Study of Serine Racemase Gene with Methamphetamine Psychosis

    PubMed Central

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

    2011-01-01

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

  2. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus.

    PubMed

    Colagiuri, S; Miller, J J; Edwards, R A

    1989-09-01

    This study compared the effects of adding sucrose and aspartame to the usual diet of individuals with well-controlled noninsulin-dependent diabetes mellitus (NIDDM). A double-blind, cross-over design was used with each 6-wk study period. During the sucrose period, 45 g sucrose (9% of total daily energy) was added, 10 g with each main meal and 5 g with each between-meal beverage. An equivalent sweetening quantity of aspartame (162 mg) was ingested during the aspartame period. The addition of sucrose did not have a deleterious effect on glycemic control, lipids, glucose tolerance, or insulin action. No differences were observed between sucrose and aspartame. Sucrose added as an integral part of the diabetic diet does not adversely affect metabolic control in well-controlled NIDDM subjects. Aspartame is an acceptable sugar substitute for diabetic individuals but no specific advantage over sucrose was demonstrated. PMID:2672774

  3. Effects of naltrexone on neural and subjective response to alcohol in treatment-seeking alcohol dependent patients

    PubMed Central

    Spagnolo, Primavera A.; Ramchandani, Vijay A.; Schwandt, Melanie L.; Zhang, Lishu; Blaine, Sara K.; Usala, Julie M.; Diamond, Kristie A.; Phillips, Monte J.; George, David T.; Momenan, Reza; Heilig, Markus

    2014-01-01

    Rationale Positively reinforcing properties of alcohol are in part mediated by activation of the ventral striatum (VS). Alcohol-induced release of endogenous opioids is thought to contribute to this response. Preclinical studies show that the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to do so in treatment seeking alcoholics has not been examined. Objectives To study the effects of NTX on alcohol-induced VS activation and on amygdala response to affective stimuli in treatment seeking alcohol dependent inpatients. Methods Sixty-three treatment seeking alcoholics were randomized to receive NTX (50 mg) or placebo (PLC) daily. On day 7, participants underwent an alcohol cue reactivity session, and craving was measured using the Penn Alcohol Craving Scale. On day 9, participants received a saline infusion followed by an alcohol infusion and also viewed affective stimuli in an MR scanner. Results Irrespective of medication treatment condition, the alcohol infusion did not activate the VS in the alcohol dependent patients. Unexpectedly, VS activation was greater in NTX treated patients than in the PLC group. NTX treated patients also reported increased craving in response to alcohol cue exposure, and increased subjective response to alcohol (‘high’ and ‘intoxicated’) compared to PLC subjects. No significant effects of alcohol infusion on brain response to affective stimuli were in the NTX or placebo groups. Conclusions Unlike previous findings in social drinkers, a moderate level of intoxication did not activate the VS in treatment seeking alcoholics. This is likely to reflect tolerance to the positively reinforcing properties of alcohol in this clinical population. Our findings may help explain the efficacy of NTX to reduce heavy drinking, but not to maintain abstinence. PMID:25581657

  4. Empagliflozin (BI 10773), a Potent and Selective SGLT2 Inhibitor, Induces Dose-Dependent Glucosuria in Healthy Subjects.

    PubMed

    Seman, Leo; Macha, Sreeraj; Nehmiz, Gerhard; Simons, Gudrun; Ren, Bailuo; Pinnetti, Sabine; Woerle, Hans J; Dugi, Klaus

    2013-04-01

    Empagliflozin is an orally available, selective inhibitor of sodium glucose cotransporter 2. In this study, single oral doses of empagliflozin from 0.5 to 800 mg were not associated with any clinically significant safety concerns in healthy male volunteers. The incidence of adverse events (AEs) was similar in subjects receiving placebo (22.2%) or empagliflozin (25.0%) in the single rising dose part of the study and after 50 mg empagliflozin under fed (28.6%) or fasted (28.6%) conditions. The most frequent AE was headache. No clinically relevant changes in laboratory or electrocardiogram (ECG) measurements were observed. Single oral doses of empagliflozin were rapidly absorbed, reaching peak levels after 1.0-2.1 hours. Increases in empagliflozin exposure were roughly dose-proportional and a dose-dependent increase in urinary glucose excretion was observed for empagliflozin doses up to 100 mg. After ingestion of 50 mg empagliflozin in conjunction with a high-fat, high-calorie meal, no clinically relevant changes in exposure were found, indicating that empagliflozin can be administered independent of food. Empagliflozin up to 800 mg did not generate clinically significant safety concerns in healthy male subjects. The pharmacokinetic properties of empagliflozin support once daily administration independent of food. PMID:27121669

  5. 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

  6. Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence

    PubMed Central

    Dean, Angela J.; Saunders, John B.; Jones, Rod T.; Young, Ross M.; Connor, Jason P.; Lawford, Bruce R.

    2006-01-01

    Objective: Dysphoria and depression have been cited as side effects of the opioid antagonist naltrexone. We aimed to assess whether depressive symptoms are a clinically relevant side effect in a population receiving naltrexone as a treatment for opioid dependence. Methods: We carried out a randomized controlled, open-label trial comparing rapid opiate detoxification under anesthesia and naltrexone treatment with continued methadone maintenance at the Alcohol and Drug Service, Royal Brisbane and Women's Hospital, Brisbane, Australia. The study subjects were patients stabilized on methadone maintenance treatment for heroin dependence who wished to transfer to naltrexone treatment. The Beck Depression Inventory, State–Trait Anxiety Inventory and Opiate Treatment Index subscales for heroin use and social functioning were used at baseline and follow-up assessments at 1, 2, 3 and 6 months. Results: Forty-two participants were allocated to receive naltrexone treatment, whereas 38 continued methadone maintenance as the control condition. Participants who received naltrexone did not exhibit worsening of depressive symptoms. In participants attending all follow-up assessments, there was a trend for those receiving naltrexone to exhibit an improvement in depression over time compared with the control group. Participants who were adherent to naltrexone treatment exhibited fewer depressive symptoms than those who were nonadherent. Conclusions: These results suggest that depression need not be considered a common adverse effect of naltrexone treatment or a treatment contraindication and that engaging with or adhering to naltrexone treatment may be associated with fewer depressive symptoms. PMID:16496034

  7. Dissociations between interval timing and intertemporal choice following administration of fluoxetine, cocaine, or methamphetamine.

    PubMed

    Heilbronner, Sarah R; Meck, Warren H

    2014-01-01

    The goal of our study was to characterize the relationship between intertemporal choice and interval timing, including determining how drugs that modulate brain serotonin and dopamine levels influence these two processes. In Experiment 1, rats were tested on a standard 40-s peak-interval procedure following administration of fluoxetine (3, 5, or 8 mg/kg) or vehicle to assess basic effects on interval timing. In Experiment 2, rats were tested in a novel behavioral paradigm intended to simultaneously examine interval timing and impulsivity. Rats performed a variant of the bi-peak procedure using 10-s and 40-s target durations with an additional "defection" lever that provided the possibility of a small, immediate reward. Timing functions remained relatively intact, and 'patience' across subjects correlated with peak times, indicating a negative relationship between 'patience' and clock speed. We next examined the effects of fluoxetine (5 mg/kg), cocaine (15 mg/kg), or methamphetamine (1 mg/kg) on task performance. Fluoxetine reduced impulsivity as measured by defection time without corresponding changes in clock speed. In contrast, cocaine and methamphetamine both increased impulsivity and clock speed. Thus, variations in timing may mediate intertemporal choice via dopaminergic inputs. However, a separate, serotonergic system can affect intertemporal choice without affecting interval timing directly. This article is part of a Special Issue entitled: Associative and Temporal Learning. PMID:24135569

  8. Music and Methamphetamine: Conditioned Cue-induced Increases in Locomotor Activity and Dopamine Release in Rats

    PubMed Central

    Polston, J.E.; Rubbinaccio, H.Y.; Morra, J.T.; Sell, E.M.; Glick, S.D.

    2011-01-01

    Associations between drugs of abuse and cues facilitate the acquisition and maintenance of addictive behaviors. Although significant research has been done to elucidate the role that simple discriminative or discrete conditioned stimuli (e.g., a tone or a light) play in addiction, less is known about complex environmental cues. The purpose of the present study was to examine the role of a musical conditioned stimulus by assessing locomotor activity and in vivo microdialysis. Two groups of rats were given non-contingent injections of methamphetamine (1.0 mg/kg) or vehicle and placed in standard conditioning chambers. During these conditioning sessions both groups were exposed to a continuous conditioned stimulus, in the form of a musical selection (“Four” by Miles Davis) played repeatedly for ninety minutes. After seven consecutive conditioning days subjects were given one day of rest, and subsequently tested for locomotor activity or dopamine release in the absence of drug while the musical conditioned stimulus was continually present. The brain regions examined included the basolateral amygdala, nucleus accumbens, and prefrontal cortex. The results show that music is an effective contextual conditioned stimulus, significantly increasing locomotor activity after repeated association with methamphetamine. Furthermore, this musical conditioned stimulus significantly increased extracellular dopamine levels in the basolateral amygdala and nucleus accumbens. These findings support other evidence showing the importance of these brain regions in conditioned learning paradigms, and demonstrate that music is an effective conditioned stimulus warranting further investigation. PMID:21145911

  9. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    PubMed

    de la Torre, Rafael; Yubero-Lahoz, Samanta; Pardo-Lozano, Ricardo; Farré, Magí

    2012-01-01

    In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI) of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer (PM) phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies. PMID:23162568

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

    PubMed Central

    Ballard, Michael E.; Dean, Andy C.; Mandelkern, Mark A.; London, Edythe D.

    2015-01-01

    Background Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence. Methods Methamphetamine users and non-user controls (n = 18 per group) completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride. Results The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008), but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622). The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010), but not methamphetamine users (r = 0.281, p = 0.258), and the group-wise interaction was significant (p = 0.030). Conclusions These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls. PMID:26657223

  11. Nucleus Accumbens Invulnerability to Methamphetamine Neurotoxicity

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

    BACKGROUND Vaccines have treatment potential for methamphetamine (MA) addiction. We tested whether a conjugate vaccine against MA (succinyl-methamphetamine–keyhole limpet hemocyanin carrier protein; SMA-KLH) would generate MA antibodies and alter MA-induced behaviors. METHODS Mice were injected with SMA-KLH and received booster administrations 3-and 20-weeks later. Serum antibody titers reached peak levels by 4–6 weeks, remained at a modest level through 18-weeks, peaked again at 22-wks after the second boost, and were still elevated at 35-weeks. At 7 weeks, groups of vaccinated and non-vaccinated mice were administered one of three MA doses (1, 2, or 3 mg/kg) to assess locomotor activity. RESULTS Non-vaccinated mice showed dose-dependent effects of MA with hypolocomotion at the lowest dose and elevated activity levels at the highest dose. Both dose effects were reduced in SMA-KLH groups, particularly low dose-induced hypolocomotion at later times post MA administration. Separate groups of vaccinated and non-vaccinated mice were trained in MA place conditioning at 30-weeks with either 0 (vehicle) or 0.5 mg/kg MA. Although times spent in the MA-paired side did not differ between groups on Test vs. Baseline sessions, SMA-KLH mice conditioned with MA showed reduced conditioned approach behaviors and decreased conditioned activity levels compared to control groups. CONCLUSION These data suggest SMA-KLH attenuates the ability of MA to support place conditioning and reduces or delays its locomotor effects. Overall, results support SMA-KLH as a candidate MA vaccine. PMID:23022610

  13. Pharmacological effects of two anti-methamphetamine monoclonal antibodies

    PubMed Central

    Laurenzana, Elizabeth M; Stevens, Misty W; Frank, John C; Hambuchen, Michael D; Hendrickson, Howard P; White, Sarah J; Williams, D Keith; Owens, S Michael; Gentry, W Brooks

    2014-01-01

    This lead candidate selection study compared two anti-(+)-methamphetamine (METH) monoclonal antibodies (mAb) to determine their ability to reduce METH-induced locomotor effects and redistribute METH and (+)-amphetamine (AMP) in a preclinical overdose model. Both mAbs have high affinity for METH, but mAb4G9 has moderate and mAb7F9 has low affinity for AMP. In the placebo-controlled behavioral experiment, the effects of each mAb on the locomotor response to a single 1 mg/kg intravenous (IV) METH dose were determined in rats. The doses of mAb binding sites were administered such that they equaled 1, 0.56, 0.32, and 0.1 times the molar equivalent (mol-eq) of METH in the body 30 min after the METH dose. METH disposition was determined in separate animals that similarly received either a 1 or 0.32 mol-eq dose of mAb binding sites 30 min after a 1 mg/kg METH dose. Total METH-induced distance traveled was significantly reduced in rats that received the highest three doses of each mAb compared with saline. The duration of METH effects was also significantly reduced by mAb7F9 at the highest dose. The disposition of METH was altered dose-dependently by both mAbs as shown in reductions of volume of distribution and total clearance, and increases in elimination half-life. These data indicate that both mAbs are effective at reducing METH-induced behavior and favorably altering METH disposition. Both were therefore suitable for further preclinical testing as potential human medications for treating METH use; however, due to results reported here and in later studies, mAb7F9 was selected for clinical development. PMID:25483484

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

    PubMed Central

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

    2015-01-01

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

  15. Duration of detection of methamphetamine in hair after abstinence.

    PubMed

    Suwannachom, Natiprada; Thananchai, Thiwaphorn; Junkuy, Anongphan; O'Brien, Timothy E; Sribanditmongkol, Pongruk

    2015-09-01

    Researchers in the field of hair analysis have known for at least two decades that test results for many chemical compounds remain positive for a considerable period of time after subjects have reported cessation of use. These findings were generally based on small sample populations or individual case studies. Within the last decade, hair analyses of larger populations have investigated the phenomenon of residual positives in abstinent individuals in order to determine the period of time required for various compounds to present negative hair test results at internationally accepted cutoff levels. Such data has primarily been used to establish guidelines for retesting former abusers of illicit drugs in order to evaluate claims of abstinence. To date, research has focused on cocaine and opiates. The present study is the first to examine the duration of detection of methamphetamine (MA) and its metabolite amphetamine (AP) in the hair of chronic MA users who recently ceased their consumption of the drug. The study population (n=63) consisted of inpatients at a hospital drug rehabilitation program in Chiang Mai, Thailand. Drug taking behavior was collected by personal interview at the time of enrollment. Subjects provided hair samples at approximately monthly intervals for MA and AP analysis by gas chromatography-mass spectrometry at 0.2ng/mg cutoff levels. The correlation of baseline MA and AP concentrations in hair at the beginning of abstinence with corresponding duration of detection indicated great individual variability for the rate of clearance of MA and AP from hair. In regard to duration of detection, the majority of chronic MA users remained MA positive for up to about 90 days of reported abstinence, but by 120 days, the detection rate had fallen to about 16%. All subjects tested negative for MA after 153 days of abstinence. For AP, the limit of the duration of detection was reached at 106 days. With the adoption of a margin of safety to compensate for

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

    PubMed Central

    Leech, Ronald; Stark, Jeffrey G.

    2013-01-01

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

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

    PubMed

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

    2016-01-01

    Methamphetamine has powerful stimulant and euphoric effects that are experienced as rewarding and encourage use. Methamphetamine addiction is associated with debilitating illnesses, destroyed relationships, child neglect, violence, and crime; but after many years of research, broadly effective medications have not been identified. Individual differences that may impact not only risk for developing a methamphetamine use disorder but also affect treatment response have not been fully considered. Human studies have identified candidate genes that may be relevant, but lack of control over drug history, the common use or coabuse of multiple addictive drugs, and restrictions on the types of data that can be collected in humans are barriers to progress. To overcome some of these issues, a genetic animal model comprised of lines of mice selectively bred for high and low voluntary methamphetamine intake was developed to identify risk and protective alleles for methamphetamine consumption, and identify therapeutic targets. The mu opioid receptor gene was supported as a target for genes within a top-ranked transcription factor network associated with level of methamphetamine intake. In addition, mice that consume high levels of methamphetamine were found to possess a nonfunctional form of the trace amine-associated receptor 1 (TAAR1). The Taar1 gene is within a mouse chromosome 10 quantitative trait locus for methamphetamine consumption, and TAAR1 function determines sensitivity to aversive effects of methamphetamine that may curb intake. The genes, gene interaction partners, and protein products identified in this genetic mouse model represent treatment target candidates for methamphetamine addiction. PMID:27055611

  18. Characterizing prefrontal cortical activity during inhibition task in methamphetamine-associated psychosis versus schizophrenia: a multi-channel near-infrared spectroscopy study.

    PubMed

    Okada, Naohiro; Takahashi, Katsuyoshi; Nishimura, Yukika; Koike, Shinsuke; Ishii-Takahashi, Ayaka; Sakakibara, Eisuke; Satomura, Yoshihiro; Kinoshita, Akihide; Takizawa, Ryu; Kawasaki, Shingo; Nakakita, Mayumi; Ohtani, Toshiyuki; Okazaki, Yuji; Kasai, Kiyoto

    2016-03-01

    Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use. PMID:25619621

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2009-08-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  2. 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

  3. Methamphetamine Exposure Combined with HIV-1 Disease or gp120 Expression: Comparison of Learning and Executive Functions in Humans and Mice

    PubMed Central

    Kesby, James P; Heaton, Robert K; Young, Jared W; Umlauf, Anya; Woods, Steven P; Letendre, Scott L; Markou, Athina; Grant, Igor; Semenova, Svetlana

    2015-01-01

    Methamphetamine dependence is a common comorbid condition among people living with HIV, and may exacerbate HIV-associated neurocognitive disorders. Animal models of neuroAIDS suggest that the gp120 protein may also cause cognitive impairment. The present work evaluated the separate and combined effects of HIV/gp120 and methamphetamine on learning and executive functions in both humans and transgenic mice. Human participants were grouped by HIV serostatus (HIV+ or HIV−) and lifetime methamphetamine dependence (METH+ or METH−). A neurocognitive test battery included domain-specific assessments of learning and executive functions. Mice (gp120+ and gp120−) were exposed to either a methamphetamine binge (METH+) or saline (METH−), then tested in the attentional-set-shifting task to assess learning and executive functions. In humans, HIV status was associated with significant impairments in learning, but less so for executive functions. The frequency of learning impairments varied between groups, with the greatest impairment observed in the HIV+/METH+ group. In mice, gp120 expression was associated with impairments in learning but not reversal learning (executive component). The greatest proportion of mice that failed to complete the task was observed in the gp120+/METH+ group, suggesting greater learning impairments. Our cross-species study demonstrated that HIV in humans and gp120 in mice impaired learning, and that a history of methamphetamine exposure increased the susceptibility to HIV-associated neurocognitive deficits in both species. Finally, the similar pattern of results in both species suggest that the gp120 protein may contribute to HIV-associated learning deficits in humans. PMID:25652249

  4. Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity.

    PubMed

    Preuss, U W; Soyka, M; Bahlmann, M; Wenzel, K; Behrens, S; de Jonge, S; Krüger, M; Bondy, B

    2000-09-25

    The aim of this study was to investigate [3H]paroxetine binding and impulsivity in alcohol-dependent and age-matched control subjects in relation to a 5'-promoter region serotonin transporter (5-HTT) polymorphism (5-HTTLPR). Alcohol-dependent subjects were hypothesized to show a decreased number of bindings sites and a lower dissociation constant. 5-HTTLPR S-genotype carriers in both alcohol-dependent and control subjects were expected to show significantly fewer binding sites and a lower dissociation constant. Influences of impulsive traits, chronic daily alcohol intake, duration of alcohol dependence, age of onset and age on [3H]paroxetine binding were also investigated. Inpatients meeting DSM IV alcohol dependence criteria and of German descent were recruited to avoid ethnic stratification effects. One hundred and seventeen control subjects of similar social status were recruited from a town community. Blood samples were taken from both alcohol-dependent and control subjects to determine 5-HTTLPR genotypes using PCR of lymphocyte DNA, and to perform platelet [3H]paroxetine binding (binding capacity: B(max); and dissociation constant: K(D)). Impulsivity was assessed using the Barratt impulsiveness scale version 5 (BIS-5) in alcohol-dependent subjects only. Alcohol-dependent subjects were subdivided into low or high impulsivity groups using a median-split of the BIS-5 scale. The control group was slightly older than the alcohol-dependent group (not statistically significant). [3H]paroxetine binding was investigated in 72 control subjects and 72 patients, of which five patients met type 2 alcohol dependence criteria. Genotyping was carried out in all patients and control subjects. A significant influence of duration of alcohol dependence was found on the [3H]paroxetine binding K(D) but not B(max.) Neither alcohol-dependent nor control subjects showed any differences in B(max) or K(D). S-allele carriers did not show a decreased binding or lower dissociation constant

  5. Profound reduction in sensitivity to the aversive effects of methamphetamine in mice bred for high methamphetamine intake

    PubMed Central

    Shabani, Shkelzen; McKinnon, Carrie S.; Cunningham, Christopher L.; Phillips, Tamara J.

    2011-01-01

    Reduced sensitivity to aversive effects of methamphetamine (MA) may increase risk for MA abuse. Studies in two replicate sets of mouse lines that were selectively bred for high and low levels of MA intake support this view. Current studies examined the extent of insensitivity to aversive MA effects of mice bred for high levels of MA drinking. Conditioning procedures in which drugs are delivered shortly after cue exposure have been used to detect aversive drug effects and, in some cases, are more sensitive to such effects. Aversive effects induced by MA injected immediately after exposure to cues from two different sensory modalities were examined. In addition, effects of higher MA doses than those used previously were examined. MA-associated place conditioning utilized tactile cues, whereas MA-induced taste conditioning utilized a novel tastant. Second replicate, MA high drinking (MAHDR-2) and low drinking (MALDR-2) mice were treated with doses of MA up to 4 mg/kg. MAHDR-2 mice were insensitive to aversive effects of MA, except after place conditioning with the 4 mg/kg dose; MALDR-2 mice exhibited sensitivity to aversive effects of MA at doses as low as 1 mg/kg. These studies show that the expression of aversion is dependent upon procedure and MA dose, and that MAHDR-2 mice have markedly reduced sensitivity to the aversive effects of MA. The current and previous results support a strong genetic relationship between level of MA intake and level of sensitivity to aversive effects of MA, a factor that could impact risk for MA use in humans. PMID:22118879

  6. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

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

  10. Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects.

    PubMed Central

    Bogardus, C; Lillioja, S; Howard, B V; Reaven, G; Mott, D

    1984-01-01

    The relationships between insulin secretion, insulin action, and fasting plasma glucose concentration (FPG) were examined in 34 southwest American Indians (19 nondiabetics, 15 noninsulin-dependent diabetics) who had a broad range of FPG (88-310 mg/100 ml). Fasting, glucose-stimulated, and meal-stimulated plasma insulin concentrations were negatively correlated with FPG in diabetics but not in nondiabetics. In contrast, fasting and glucose-stimulated plasma C-peptide concentrations did not decrease with increasing FPG in either group and 24-h urinary C-peptide excretion during a diet of mixed composition was positively correlated with FPG for all subjects (r = 0.36, P less than 0.05). Fasting free fatty acid (FFA) was correlated with FPG in nondiabetics (r = 0.49, P less than 0.05) and diabetics (r = 0.77, P less than 0.001). Fasting FFA was also correlated with the isotopically determined endogenous glucose production rate in the diabetics (r = 0.54, P less than 0.05). Endogenous glucose production was strongly correlated with FPG in the diabetics (r = 0.90, P less than 0.0001), but not in the nondiabetics. Indirect calorimetry showed that FPG was also negatively correlated with basal glucose oxidation rates (r = -0.61, P less than 0.001), but positively with lipid oxidation (r = 0.74, P less than 0.001) in the diabetics. Insulin action was measured as total insulin-mediated glucose disposal, glucose oxidation, and storage rates, using the euglycemic clamp with simultaneous indirect calorimetry at plasma insulin concentrations of 135 +/- 5 and 1738 +/- 59 microU/ml. These parameters of insulin action were significantly, negatively correlated with FPG in the nondiabetics at both insulin concentrations, but not in the diabetics although all the diabetics had markedly decreased insulin action. We conclude that decreased insulin action is present in the noninsulin-dependent diabetics in this population and marked hyperglycemia occurs with the addition of decreased

  11. Expression of TNF-Alpha-Dependent Apoptosis-Related Genes in the Peripheral Blood of Malagasy Subjects with Tuberculosis

    PubMed Central

    Rakotosamimanana, Niaina; Doherty, T. Mark; Andriamihantasoa, Lova H.; Richard, Vincent; Gicquel, Brigitte; Soares, Jean-Louis; Zumla, Alimuddin; Razanamparany, Voahangy Rasolofo

    2013-01-01

    The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective “protective immunity” against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis. Newly diagnosed tuberculosis patients (n = 23), their close household contacts (n = 80), and community controls (n = 46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up. Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes. These data suggest tuberculosis may be associated with

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    2008-03-01

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

  17. Methamphetamine Users Have Increased Dental Disease: A Propensity Score Analysis.

    PubMed

    Shetty, V; Harrell, L; Clague, J; Murphy, D A; Dye, B A; Belin, T R

    2016-07-01

    Methamphetamine (MA) users are assumed to have a high burden of tooth decay. Less clear is how the distribution and severity of dental caries in MA users differ from the general population. Using a covariate-balancing propensity score strategy, we investigated the differential effects of MA use on dental caries by comparing the patterns of decayed, missing, and filled teeth in a community sample of 571 MA users with a subset of 2,755 demographically similar control individuals selected from a National Health and Nutrition Examination Survey (NHANES) cohort. Recruited over a 2-y period with a stratified sampling protocol, the MA users underwent comprehensive dental examinations by 3 trained and calibrated dentists using NHANES protocols. Propensity scores were estimated with logistic regression based on background characteristics, and a subset of closely matched subjects was stratified into quintiles for comparisons. MA users were twice as likely to have untreated caries (odds ratio [OR] = 2.08; 95% confidence interval [95% CI]: 1.55 to 2.78) and 4 times more likely to have caries experience (OR = 4.06; 95% CI: 2.24 to 7.34) than the control group of NHANES participants. Additionally, MA users were twice as likely to have 2 more decayed, missing, or filled teeth (OR = 2.08; 95% CI: 1.29 to 2.79) than the NHANES participants. The differential involvement of the teeth surfaces in MA users was quite distinctive, with carious surface involvement being highest for the maxillary central incisors, followed by maxillary posterior premolars and molars. Users injecting MA had significantly higher rates of tooth decay compared with noninjectors (P = 0.04). Although MA users experienced decayed and missing dental surfaces more frequently than NHANES participants, NHANES participants had more restored surfaces, especially on molars. The high rates and distinctive patterns of dental caries observed could be used 1) to alert dentists to covert MA use in their patients and 2) as

  18. The pH Levels of Different Methamphetamine Drug Samples on the Street Market in Cape Town

    PubMed Central

    Grobler, Sias R.; Chikte, Usuf; Westraat, Jaco

    2011-01-01

    The purpose of this study was to determine the pH levels of 29 different samples of methamphetamine on the street market in Cape Town. The sample was dissolved in water and the pH of each sample determined. The pH levels varied from 3.02 to 7.03 with an average of 5.0. Seventy-two percent (21) of the samples had a pH level below the saliva “critical pH point of 5.6” and therefore should cause significant damage to enamel, especially in hyposalivation subjects without a saliva flow. However, about 26% of the samples had a pH level close to the neutral point and should cause minor damage to enamel. To lessen enamel damage, subjects should exercise good oral hygiene practice, rinse with a fluoride-containing mouth rinse, drink artificially sweetened drinks, and eat cheese. It is concluded that most of the methamphetamine samples have a low enough pH to cause direct damage to enamel especially in hyposalivation subjects. PMID:21991491

  19. Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

    PubMed Central

    Mayo, Leah M; de Wit, Harriet

    2015-01-01

    Drug-associated cues elicit conditioned responses in human drug users, and are thought to facilitate a drug-seeking behavior. Yet, little is known about how these associations are acquired, or about the specificity of the conditioned response modalities. In this study, healthy, nondependent volunteers (N=90) completed a conditioning paradigm in which they received a moderate dose of methamphetamine paired with one stimulus and placebo with another stimulus, each on two separate occasions. Their responses to these cues were measured with a behavioral preference, self-reported ‘liking', emotional reactivity, and attentional bias measures, both before and after the conditioning. Following the conditioning procedure, subjects exhibited a behavioral preference, positive emotional reactivity, and attentional bias toward the methamphetamine-associated cue, compared with the placebo stimulus. In addition, subjects who reported greater positive subjective drug effects during the conditioning displayed a more robust conditioning. This work demonstrates that healthy nondependent volunteers readily acquire conditioned responses to neutral stimuli paired with a drug. The procedure has significant value to study individual variation in acquisition of conditioned responses as a possible risk factor for drug taking, and to study the neural basis of conditioned drug responses. PMID:25601231

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

    PubMed

    Banks, Matthew L; Blough, Bruce E

    2015-08-01

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

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

    PubMed Central

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

    1979-01-01

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

  2. Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine

    PubMed Central

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

    2013-01-01

    Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as ‘bath salts’ that have gained popularity amongst drug abusers. PMID:23892199

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

    PubMed

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

    2014-02-27

    Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as 'bath salts' that have gained popularity among drug abusers. PMID:23892199

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

    PubMed

    Dayrit, Fabian M; Dumlao, Morphy C

    2004-08-11

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

  5. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2013-01-01

    Relapse rates following current methamphetamine abuse treatments are very high (∼40–60%), and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders) that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-Ab/mMOG-35-55), in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.). Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2) levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments. PMID:23460798

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

    SciTech Connect

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

    2010-12-01

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

  9. Preclinical Efficacy of N-Substituted Benztropine Analogs as Antagonists of Methamphetamine Self-Administration in Rats

    PubMed Central

    Hiranita, Takato; Kohut, Stephen J.; Soto, Paul L.; Tanda, Gianluigi; Kopajtic, Theresa A.

    2014-01-01

    Atypical dopamine-uptake inhibitors have low abuse potential and may serve as leads for development of cocaine-abuse treatments. Among them, the benztropine (BZT) derivatives, N-butyl (JHW007), N-allyl (AHN2-005), and N-methyl (AHN1-055) analogs of 3α-[bis(4′-fluorophenyl)methoxy]-tropane dose-dependently decreased cocaine self-administration without effects on food-maintained responding. Our study examined selectivity by assessing their effects on self-administration of other drugs. As with cocaine, each BZT analog (1.0–10.0 mg/kg i.p.) dose-dependently decreased maximal self-administration of d-methamphetamine (0.01–0.32 mg/kg/infusion) but was inactive against heroin (1.0–32.0 µg/kg/infusion) and ketamine (0.032–1.0 mg/kg/infusion) self-administration. Further, standard dopamine indirect-agonists [WIN35,428 ((−)-3β-(4-fluorophenyl)-tropan-2-β-carboxylic acid methyl ester tartrate), d-amphetamine (0.1–1.0 mg/kg i.p., each)] dose-dependently left-shifted self-administration dose-effect curves for d-methamphetamine, heroin, and ketamine. Noncompetitive NMDA-glutamate receptor/channel antagonists [(+)-MK-801 (0.01–0.1 mg/kg i.p.), memantine (1.0–10.0 mg/kg i.p.)] also left-shifted dose-effect curves for d-methamphetamine and ketamine (but not heroin) self-administration. The µ-agonists [dl-methadone and morphine (1.0–10.0 mg/kg i.p., each)] dose-dependently decreased maximal self-administration of µ-agonists (heroin, remifentanil) but not d-methamphetamine or ketamine self-administration. The µ-agonist-induced decreases were similar to the effects of BZT analogs on stimulant self-administration and effects of food prefeeding on responding maintained by food reinforcement. Radioligand-binding and behavioral studies suggested that inhibition of dopamine transporters and σ receptors were critical for blocking stimulant self-administration by BZT-analogs. Thus, the present results suggest that the effects of BZT analogs on stimulant self

  10. Preclinical efficacy of N-substituted benztropine analogs as antagonists of methamphetamine self-administration in rats.

    PubMed

    Hiranita, Takato; Kohut, Stephen J; Soto, Paul L; Tanda, Gianluigi; Kopajtic, Theresa A; Katz, Jonathan L

    2014-01-01

    Atypical dopamine-uptake inhibitors have low abuse potential and may serve as leads for development of cocaine-abuse treatments. Among them, the benztropine (BZT) derivatives, N-butyl (JHW007), N-allyl (AHN2-005), and N-methyl (AHN1-055) analogs of 3α-[bis(4'-fluorophenyl)methoxy]-tropane dose-dependently decreased cocaine self-administration without effects on food-maintained responding. Our study examined selectivity by assessing their effects on self-administration of other drugs. As with cocaine, each BZT analog (1.0-10.0 mg/kg i.p.) dose-dependently decreased maximal self-administration of d-methamphetamine (0.01-0.32 mg/kg/infusion) but was inactive against heroin (1.0-32.0 µg/kg/infusion) and ketamine (0.032-1.0 mg/kg/infusion) self-administration. Further, standard dopamine indirect-agonists [WIN35,428 ((-)-3β-(4-fluorophenyl)-tropan-2-β-carboxylic acid methyl ester tartrate), d-amphetamine (0.1-1.0 mg/kg i.p., each)] dose-dependently left-shifted self-administration dose-effect curves for d-methamphetamine, heroin, and ketamine. Noncompetitive NMDA-glutamate receptor/channel antagonists [(+)-MK-801 (0.01-0.1 mg/kg i.p.), memantine (1.0-10.0 mg/kg i.p.)] also left-shifted dose-effect curves for d-methamphetamine and ketamine (but not heroin) self-administration. The µ-agonists [dl-methadone and morphine (1.0-10.0 mg/kg i.p., each)] dose-dependently decreased maximal self-administration of µ-agonists (heroin, remifentanil) but not d-methamphetamine or ketamine self-administration. The µ-agonist-induced decreases were similar to the effects of BZT analogs on stimulant self-administration and effects of food prefeeding on responding maintained by food reinforcement. Radioligand-binding and behavioral studies suggested that inhibition of dopamine transporters and σ receptors were critical for blocking stimulant self-administration by BZT-analogs. Thus, the present results suggest that the effects of BZT analogs on stimulant self-administration are

  11. An animal model of differential genetic risk for methamphetamine intake

    PubMed Central

    Phillips, Tamara J.; Shabani, Shkelzen

    2015-01-01

    The question of whether genetic factors contribute to risk for methamphetamine (MA) use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine-associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1) agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the development of a

  12. The relationship between methamphetamine use and increased dental disease

    PubMed Central

    Shetty, Vivek; Mooney, Larissa J.; Zigler, Corwin M.; Belin, Thomas R.; Murphy, Debra; Rawson, Richard

    2010-01-01

    Background Methamphetamine (MA) use has been linked anecdotally to rampant dental disease. The authors sought to determine the relative prevalence of dental comorbidities in MA users, verify whether MA users have more quantifiable dental disease and report having more dental problems than nonusers and establish the influence of mode of MA administration on oral health outcomes. Methods Participating physicians provided comprehensive medical and oral assessments for adults dependent on MA (n = 301). Trained interviewers collected patients' self-reports regarding oral health and substance-use behaviors. The authors used propensity score matching to create a matched comparison group of nonusers from participants in the the Third National Health and Nutrition Examination Survey (NHANES III). Results Dental or oral disease was one of the most prevalent (41.3 percent) medical cormorbidities in MA users who otherwise were generally healthy. On average, MA users had significantly more missing teeth than did matched NHANES III control participants (4.58 versus 1.96, P < .001) and were more likely to report having oral health problems (P < .001). Significant subsets of MA users expressed concerns with their dental appearance (28.6 percent), problems with broken or loose teeth (23.3 percent) and tooth grinding (bruxism) or erosion (22.3 percent). The intravenous use of MA was significantly more likely to be associated with missing teeth than was smoking MA (odds ratio = 2.47; 95 percent confidence interval = 1.3-4.8). Conclusions Overt dental disease is one of the key distinguishing comorbidities in MA users. MA users have demonstrably higher rates of dental disease and report long-term unmet oral health needs. Contrary to common perception, users who smoke or inhale MA have lower rates of dental disease than do those who inject the drug. Many MA users are concerned with the cosmetic aspects of their dental disease, and these concerns could be used as behavioral triggers for

  13. Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

    PubMed Central

    Castelli, M. Paola; Casu, Angelo; Casti, Paola; Scherma, Maria; Fattore, Liana; Fadda, Paola; Ennas, M. Grazia

    2014-01-01

    Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS), production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4×10 mg/kg, 2 hours apart) were pre- or post-treated with Δ9-THC (1 or 3 mg/kg) and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP). Results showed that, as compared to corresponding controls (i) METH-induced nNOS overexpression in the caudate-putamen (CPu) was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (−19% and −28% for 1 mg/kg pre- and post-treated animals; −25% and −21% for 3 mg/kg pre- and post-treated animals); (ii) METH-induced GFAP-immunoreactivity (IR) was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (−50%) and by pre-treatment with 3 mg/kg Δ9-THC (−53%); (iii) METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC) by pre- and post-treatment with both doses of Δ9-THC (−34% and −47% for 1 mg/kg pre- and post-treated animals; −37% and −29% for 3 mg/kg pre- and post-treated animals). The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    PubMed

    Verweij, A M

    1989-06-01

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

  16. Methamphetamine exposure and chronic illness in police officers

    PubMed Central

    Ross, Gerald H; Sternquist, Marie C

    2012-01-01

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

  17. Methamphetamine use and malnutrition among street-involved youth

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2007-12-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... methamphetamine salts (d-desoxyephedrine, or dl-desoxyephedrine, or their salts), as well as amphetamine inhalers... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and...

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

    ERIC Educational Resources Information Center

    Yacoubian, George S.

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Skeers, Vicki M.

    1992-01-01

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

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

    ERIC Educational Resources Information Center

    Armstrong, Todd A.; Armstrong, Gaylene S.

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Eitle, David J.; Eitle, Tamela McNulty

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  14. 75 FR 13702 - Implementation of the Methamphetamine Production Prevention Act of 2008

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

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

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

    ERIC Educational Resources Information Center

    Stretesky, Paul B.

    2009-01-01

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

  16. Flicker-induced retinal vasodilatation is not dependent on complement factor H polymorphism in healthy young subjects

    PubMed Central

    Told, Reinhard; Palkovits, Stefan; Boltz, Agnes; Schmidl, Doreen; Napora, Katarzyna J; Werkmeister, René M; Haslacher, Helmuth; Frantal, Sophie; Popa-Cherecheanu, Alina; Schmetterer, Leopold; Garhöfer, Gerhard

    2014-01-01

    Purpose The complement factor H (CFH) tyrosine 402 histidine (Y402H, rs1061170) variant is known to be significantly associated with age-related macular degeneration (AMD). Whether this genetic variant may impact retinal blood flow regulation is largely unknown. This study investigated whether flicker-induced vasodilation, an indicator for the coupling between neural activity and blood flow, is altered in subjects carrying the rs1061170 risk allele. Methods One hundred healthy subjects (aged between 18 and 45 years) were included in this study. Retinal blood flow regulation was tested by assessing retinal vessel calibres in response to stimulation with diffuse flicker light. Retinal vascular flicker responses were determined with a Dynamic Vessel Analyzer (DVA). In addition, genotyping for rs1061170 was performed. Results Eighteen subjects were homozygous for the risk allele C, 50 were homozygous for the ancestral allele T, and 31 subjects were heterozygous (CT). One subject had to be excluded from data evaluation, as no genetic analysis could be performed due to technical difficulties. Baseline diameters of retinal arteries (p = 0.39) and veins (p = 0.64) were comparable between the three groups. Flicker-induced vasodilation in both retinal arteries (p = 0.38) and retinal veins (p = 0.62) was also comparable between the three studied groups. Conclusions Our data indicate that homozygous healthy young carriers of the C risk allele at rs1061170 do not show abnormal flicker-induced vasodilation in the retina. This suggests that the high-risk genetic variant of CFH polymorphism does not impact neuro-vascular coupling in healthy subjects. PMID:24863099

  17. A pilot trial of integrated behavioral activation and sexual risk reduction counseling for HIV-uninfected men who have sex with men abusing crystal methamphetamine.

    PubMed

    Mimiaga, Matthew J; Reisner, Sari L; Pantalone, David W; O'Cleirigh, Conall; Mayer, Kenneth H; Safren, Steven A

    2012-11-01

    Crystal methamphetamine use is a major driver behind high-risk sexual behavior among men who have sex with men (MSM). Prior work suggests a cycle of continued crystal methamphetamine use and high-risk sex due to loss of the ability to enjoy other activities, which appears to be a side effect of this drug. Behavioral activation (BA) is a treatment for depression that involves learning to reengage in life's activities. We evaluated a novel intervention for crystal methamphetamine abuse and high-risk sex in MSM, incorporating 10 sessions of BA with integrated HIV risk reduction counseling (RR). Forty-four subjects were screened, of whom 21 met initial entry criteria. A total of 19 participants enrolled; 16 completed an open-phase study of the intervention. Behavioral assessments were conducted at baseline, 3 months postbaseline, and 6 months postbaseline. Linear mixed effects regression models were fit to assess change over time. Mean unprotected anal intercourse (UAI) episodes decreased significantly from baseline to acute postintervention (β=-4.86; 95% confidence interval [CI]=-7.48, -2.24; p=0.0015) and from baseline to 6 months postbaseline (β=-5.07; 95% CI=-7.85, -2.29; p=0.0017; test of fixed effects χ(2)=16.59; df=2,13; p=0.0002). On average, there was a significant decrease over time in the number of crystal methamphetamine episodes in the past 3 months (χ(2)=22.43; df=2,15; p<0.0001), and the number of days of crystal methamphetamine use in the past 30 days (χ(2)=9.21; df=2,15; p=0.010). Statistically significant reductions in depressive symptoms and poly-substance use were also maintained. Adding behavioral activation to risk reduction counseling for MSM with problematic crystal methamphetamine use may augment the potency of a risk reduction intervention for this population. Due to the small sample size and time intensive intervention, future testing in a randomized design is necessary to determine efficacy, with subsequent effectiveness testing. PMID

  18. Homogenizing the 2 X 2 Contingency Table: A Method for Removing Dependencies Due to Subject and Item Differences.

    ERIC Educational Resources Information Center

    Flexser, Arthur J.

    1981-01-01

    Contingency analyses have been employed to assess the degree to which outcomes of successive tests of corresponding items deviate from stochastic independence. A method of adjusting contingency tables to remove the effects of subject and item inhomogeneities, is presented. The method represents a partial solution to the "Simpson's paradox"…

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

    PubMed

    Connell-Carrick, Kelli

    2007-01-01

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

  20. Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS)

    PubMed Central

    Santos-Pontelli, Taiza E. G.; Rimoli, Brunna P.; Favoretto, Diandra B.; Mazin, Suleimy C.; Truong, Dennis Q.; Leite, Joao P.; Pontes-Neto, Octavio M.; Babyar, Suzanne R.; Reding, Michael; Bikson, Marom; Edwards, Dylan J.

    2016-01-01

    Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients. PMID:27031726

  1. Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

    PubMed

    Santos-Pontelli, Taiza E G; Rimoli, Brunna P; Favoretto, Diandra B; Mazin, Suleimy C; Truong, Dennis Q; Leite, Joao P; Pontes-Neto, Octavio M; Babyar, Suzanne R; Reding, Michael; Bikson, Marom; Edwards, Dylan J

    2016-01-01

    Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients. PMID:27031726

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

    PubMed Central

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

    2016-01-01

    Background: The C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) is a nontoxic peptide with demonstrated in vitro and in vivo neuroprotective effects against striatal dopaminergic damage induced by 1-methyl-4-phenylpyridinium and 6-hydoxydopamine, suggesting its possible therapeutic potential in Parkinson’s disease. Methamphetamine, a widely abused psychostimulant, has selective dopaminergic neurotoxicity in rodents, monkeys, and humans. This study was undertaken to determine whether Hc-TeTx might also protect against methamphetamine-induced dopaminergic neurotoxicity and the consequent motor impairment. Methods: For this purpose, we treated mice with a toxic regimen of methamphetamine (4mg/kg, 3 consecutive i.p. injections, 3 hours apart) followed by 3 injections of 40 ug/kg of Hc-TeTx into grastrocnemius muscle at 1, 24, and 48 hours post methamphetamine treatment. Results: We found that Hc-TeTx significantly reduced the loss of dopaminergic markers tyrosine hydroxylase and dopamine transporter and the increases in silver staining (a well stablished degeneration marker) induced by methamphetamine in the striatum. Moreover, Hc-TeTx prevented the increase of neuronal nitric oxide synthase but did not affect microglia activation induced by methamphetamine. Stereological neuronal count in the substantia nigra indicated loss of tyrosine hydroxylase-positive neurons after methamphetamine that was partially prevented by Hc-TeTx. Importantly, impairment in motor behaviors post methamphetamine treatment were significantly reduced by Hc-TeTx. Conclusions: Here we demonstrate that Hc-TeTx can provide significant protection against acute methamphetamine-induced neurotoxicity and motor impairment, suggesting its therapeutic potential in methamphetamine abusers. PMID:26945022

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

    PubMed Central

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

    2014-01-01

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

  4. 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. PMID:22458709

  5. Amphetamine Dependence and Co-Morbid Alcohol Abuse: Associations to Brain Cortical Thickness

    PubMed Central

    2010-01-01

    Background Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls. While all subjects were recruited to be free of alcohol dependence, structured clinical interviews revealed significant patterns of alcohol use in the patients. Structural magnetic resonance brain images were obtained from the subjects using a 1.5 Tesla GE Signa machine. Brain cortical thickness was measured with submillimeter precision at multiple finely spaced cortical locations using semi-automated post-processing (FreeSurfer). Contrast analysis of a general linear model was used to test for differences between the two groups at each cortical location. In addition to contrasting patients with controls, a number of analyses sought to identify possible confounding effects from alcohol. Results No significant cortical thickness differences were observed between the full patient group and controls, nor between non-drinking patients and controls. Patients with a history of co-morbid heavy alcohol use (n = 29) showed reductions in the superior-frontal right hemisphere and pre-central left hemisphere when compared to healthy controls (n = 40). Conclusions Amphetamine usage was associated with reduced cortical thickness only in patients co-morbid for heavy alcohol use. Since cortical thickness is but one measure of brain structure and does not capture brain function, further studies of brain structure and function in amphetamine dependence are warranted. PMID:20487539

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2012-09-01

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

  10. Effects of Educational Intervention on Health-Promoting Lifestyle and Health-Related Life quality of Methamphetamine Users and Their Families: a Randomized Clinical Trial

    PubMed Central

    Ghasemi, Afsaneh; Estebsari, Fatemeh; Bastaminia, Amir; Jamshidi, Ensiyeh; Dastoorpoor, Maryam

    2014-01-01

    Background: Family-centered empowerment of drug and stimulant users is an effective program for a better response to treatment, prevention of treatment adverse effects, and promotion quality of life (QoL) and lifestyle in the process of discontinuing drug abuse. Objectives: This study aimed to determine the effects of educational intervention, based on family-centered empowerment and Pender's health promotion models, on health-promoting lifestyle and health-related QoL among methamphetamine users and their families. Patients and Methods: In a randomized clinical trial, methamphetamine users, who were admitted to Tehran University of Medical Sciences Substance Abuse Treatment Centers, were randomly allocated to three groups: a group for training of methamphetamine users who were in recovery phase (intervention group 1;95 subjects);a group for training of a family member of methamphetamine users who were in recovery phase (intervention group 2; 95 subjects); and a control group (95 subjects). A demographic checklist and a standard questionnaire covering health-promoting lifestyle, health-related QoL, self-efficacy, perceived affect, perceived social support, and perceived barriers dimensions were used to gather required data. Independent-samples t test, paired-samples t-test, and ANCOVA were used to analyze the data. Results: Analysis of covariance showed that after adjusting for effects of pretest scores, the difference between mean post-test scores of health-promoting lifestyle scale, health-related QoL scale, and all constructs of Pender's health promotion model (self-efficacy, perceived affect, perceived social support, and perceived barriers) in the intervention group 1 and control group were significant (P< 0.0001). In addition, changes in mean scores of lifestyle scale (42.4 ± 13.6), QoL scale (29.1 ± 14.2), self-efficacy (16.1 ± 2.6), perceived affect (16.1 ± 8), social support (35.4 ± 12.4), and barriers (17.2 ± 15.8) before and after intervention were

  11. 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. PMID:25444868

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

    PubMed Central

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

    2009-01-01

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

  13. Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

    PubMed Central

    Blum, Kenneth; Chen, Amanda L. C.; Oscar-Berman, Marlene; Chen, Thomas J. H.; Lubar, Joel; White, Nancy; Lubar, Judith; Bowirrat, Abdalla; Braverman, Eric; Schoolfield, John; Waite, Roger L.; Downs, Bernard W.; Madigan, Margaret; Comings, David E.; Davis, Caroline; Kerner, Mallory M.; Knopf, Jennifer; Palomo, Tomas; Giordano, John J.; Morse, Siobhan A.; Fornari, Frank; Barh, Debmalya; Femino, John; Bailey, John A.

    2011-01-01

    Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic). Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]). Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may

  14. Methodology for determining time-dependent mechanical properties of tuff subjected to near-field repository conditions

    SciTech Connect

    Blacic, J.D.; Andersen, R.

    1983-01-01

    We have established a methodology to determine the time dependence of strength and transport properties of tuff under conditions appropriate to a nuclear waste repository. Exploratory tests to determine the approximate magnitudes of thermomechanical property changes are nearly complete. In this report we describe the capabilities of an apparatus designed to precisely measure the time-dependent deformation and permeability of tuff at simulated repository conditions. Preliminary tests with this new apparatus indicate that microclastic creep failure of tuff occurs over a narrow strain range with little precursory Tertiary creep behavior. In one test, deformation under conditions of slowly decreasing effective pressure resulted in failure, whereas some strain indicators showed a decreasing rate of strain.

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

    PubMed Central

    Messina, Nena; Jeter, Kira

    2012-01-01

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

  16. Methamphetamine and the hypothalamic-pituitary-adrenal axis

    PubMed Central

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

    2015-01-01

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

  17. Acute lead poisoning in two users of illicit methamphetamine

    SciTech Connect

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

    1987-07-31

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

  18. On a relativistic particle and a relativistic position-dependent mass particle subject to the Klein-Gordon oscillator and the Coulomb potential

    NASA Astrophysics Data System (ADS)

    Vitória, R. L. L.; Furtado, C.; Bakke, K.

    2016-07-01

    The relativistic quantum dynamics of an electrically charged particle subject to the Klein-Gordon oscillator and the Coulomb potential is investigated. By searching for relativistic bound states, a particular quantum effect can be observed: a dependence of the angular frequency of the Klein-Gordon oscillator on the quantum numbers of the system. The meaning of this behaviour of the angular frequency is that only some specific values of the angular frequency of the Klein-Gordon oscillator are permitted in order to obtain bound state solutions. As an example, we obtain both the angular frequency and the energy level associated with the ground state of the relativistic system. Further, we analyse the behaviour of a relativistic position-dependent mass particle subject to the Klein-Gordon oscillator and the Coulomb potential.

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Courtney, Kelly E.; Ray, Lara A.

    2014-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  10. Cytochrome P450 epoxygenase dependence of opioid analgesia: fluconazole does not interfere with remifentanil-mediated analgesia in human subjects.

    PubMed

    Oertel, B G; Vermehren, J; Huynh, T T; Doehring, A; Ferreiros, N; Zimmermann, M; Geisslinger, G; Lötsch, J

    2014-12-01

    Cytochrome P450 (CYP) inhibitors may reduce opioid analgesia by inhibiting CYP activity-dependent post-opioid receptor signaling pathways in the brain. This suggestion was predicated on observations of highly attenuated morphine antinociception in rodents after intracerebroventricular injection of fluconazole or carrying a neuron-specific deletion of the cytochrome P450 reductase. However, based on assessments of thermal and electrical pain tolerance, respiratory function, and side effects in 21 healthy volunteers, before and during steady-state concentrations of 1.5 and 3.0 ng/ml of remifentanil at the effect site (viz., the central nervous system), administration of 400 mg/day fluconazole for 8 days in a double-blind, placebo-controlled manner failed to attenuate opioid effects. Although CYP inhibitors such as fluconazole are unlikely to attenuate remifentanil analgesia in humans, extrapolation of the findings to other opioids is premature because differences among opioid effects, such as ligand-selective biased signaling at opioid receptors, leave the possibility that CYP-dependent opioid signaling in the brain might be limited to morphine and may not extend to remifentanil. PMID:25148377

  11. From dilatancy to contraction: Stress-dependent failure mode progression in two porous sandstones subjected to true triaxial testing

    NASA Astrophysics Data System (ADS)

    Ma, Xiaodong; Haimson, Bezalel

    2013-04-01

    Porous sedimentary rocks such as sandstones are typical oil-bearing formations in which failure due to high stress concentration is likely to occur during wellbore drilling and subsequent operations. The objective of this research was to investigate the effect of ?2 on strength, failure-plane angle, and failure mode under realistically simulated field conditions (?1 ×?2 ×?3). A series of true triaxial compression tests were conducted on two representative porous sandstones: Coconino (17.5% porosity, 99% quartz, with rounded and well-sorted 0.1 mm grains that are bonded by suturing and some quartz overgrowth), and Bentheim (24% porosity, 95% quartz, with sub-rounded 0.3 mm grains that are bonded exclusively by suturing). Square cuboidal specimens (19 x 19 x 38mm) were subjected to independent loads in three principal directions, using the University of Wisconsin testing apparatus, creating a true triaxial state of stress (?1 ×?2 ×?3). In all tests, ?3 and ?2 were maintained constant at predetermined levels, while ?1 was raised monotonically until failure occurred. The magnitude of ?3 varied between 0 and 150 MPa, covering the range of brittle behavior, brittle-ductile transition, and the threshold to the ductile zone in the weaker Bentheim sandstone. It was found that in both rocks the compressive strength (?1,peak) for a given ?3 increases as the preset ?2 is raised between tests, and reaches a peak (15% over ?1,peak when ?2 = ?3 in the Coconino, and less than 10% in the Bentheim), beyond which it gradually drops, such that when ?2 ? ?1,peak, the strength is approximately the same as when ?2 = ?3. This strengthening effect is considerably lower than that in previously tested crystalline rocks, such as Westerly granite and KTB amphibolite (more than 50%, Haimson, 2006). Plotting the test data in the ?oct vs. ?oct domain, where the two stress invariants ?oct, the octahedral shear stress, and ?oct,the mean normal stress, are both taken at failure), Coconino shows

  12. The Pharmacokinetic Exposure to Fexofenadine is Volume-Dependently Reduced in Healthy Subjects Following Oral Administration With Apple Juice.

    PubMed

    Luo, J; Imai, H; Ohyama, T; Hashimoto, S; Hasunuma, T; Inoue, Y; Kotegawa, T; Ohashi, K; Uemura, N

    2016-08-01

    Pharmacokinetic exposures to fexofenadine (FEX) are reduced by apple juice (AJ); however, the relationship between the AJ volume and the degree of AJ-FEX interaction has not been understood. In this crossover study, 10 healthy subjects received single doses of FEX 60 mg with different volumes (150, 300, and 600 mL) of AJ or water (control). To identify an AJ volume lacking clinically meaningful interaction, we tested a hypothesis that the 90% confidence interval (CI) for geometric mean ratio (GMR) of FEX AUCAJ /AUCwater is contained within a biocomparability bound of 0.5-2.0, with at least one tested volume of AJ. GMR (90% CI) of AUCAJ 150mL /AUCwater , AUCAJ 300mL /AUCwater , and AUCAJ 600mL /AUCwater were 0.903 (0.752-1.085), 0.593 (0.494-0.712), and 0.385 (0.321-0.462), respectively. While a moderate to large AJ-FEX interaction is caused by a larger volumes of AJ (e.g., 300 to 600 mL), the effect of a small volume (e.g., 150 mL) appears to be not meaningful. PMID:27197662

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

    PubMed Central

    Ahmadi, Jamshid; Ekramzadeh, Sara; Pridmore, Saxby

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2009-03-01

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

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

    PubMed

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

    2015-04-01

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

  17. Time-dependent behavior of a placed bed of cohesive sediment subjected to erosion and deposition cycles

    NASA Astrophysics Data System (ADS)

    Mariotti, G.; Valentine, K.; Fagherazzi, S.

    2015-02-01

    This study aims to explore the behavior of a cohesive sediment bed that undergoes cycles of erosion and deposition under diluted conditions. A bed of bentonite (montmorillonite) sediment was placed in two annular flumes and subjected to daily erosion tests for a period of 80 days, mimicking intermittent moderate-energy disturbances like tidal currents and wind waves. After each erosion test, the suspended sediment was allowed to settle back in the flumes. The amount of suspended sediment measured at the top of the water column at the end of each erosion test decreased in the first 5 days, concurrently with an increase in the bulk-settling velocity near the bed. This pattern is explained by turbulence-induced flocculation of clay particles and consequent formation of a surface floc layer. After about 20 days, the amount of suspended sediment measured at the top of the water column at the end of each erosion test increased and the settling velocity decreased, whereas the suspended sediment concentration measured near the bed remained nearly constant. We explain such trend by the cumulative release of slow-settling particles from the bed. This experiment suggests that the superficial layer of a placed bed that is periodically eroded and redeposited experiences competing processes: the sediment that is resuspended at every cycle becomes less erodible, but prolonged exposure to shear stress increases the pool of eroded sediment over time. The total amount of resuspended sediment seems to become constant after several tens of cycle, suggesting that the release of particles from the bed by cumulative erosion is balanced by the binding of such particles to the bed.

  18. Conceptualizing Social Recovery: Recovery Routes of Methamphetamine Users

    PubMed Central

    Boeri, Miriam; Gibson, David; Boshears, Paul

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  20. The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects

    PubMed Central

    Cotter, Rachel; Pei, Yue; Mus, Liudmila; Harmeier, Anja; Gainetdinov, Raul R.; Hoener, Marius C.; Canales, Juan J.

    2015-01-01

    The newly discovered trace amine-associated receptor 1 (TAAR1) has the ability to regulate both dopamine function and psychostimulant action. Here, we tested in rats the ability of RO5203648, a selective TAAR1 partial agonist, to modulate the physiological and behavioral effects of methamphetamine (METH). In experiment 1, RO5203468 dose- and time-dependently altered METH-induced locomotor activity, manifested as an early attenuation followed by a late potentiation of METH's stimulating effects. In experiment 2, rats received a 14-day treatment regimen during which RO5203648 was co-administered with METH. RO5203648 dose-dependently attenuated METH-stimulated hyperactivity, with the effects becoming more apparent as the treatments progressed. After chronic exposure and 3-day withdrawal, rats were tested for locomotor sensitization. RO5203648 administration during the sensitizing phase prevented the development of METH sensitization. However, RO5203648, at the high dose, cross-sensitized with METH. In experiment 3, RO5203648 dose-dependently blocked METH self-administration without affecting operant responding maintained by sucrose, and exhibited lack of reinforcing efficacy when tested as a METH's substitute. Neurochemical data showed that RO5203648 did not affect METH-mediated DA efflux and uptake inhibition in striatal synaptosomes. In vivo, however, RO5203648 was able to transiently inhibit METH-induced accumulation of extracellular DA levels in the nucleus accumbens. Taken together, these data highlight the significant potential of TAAR1 to modulate METH's neurochemical and behavioral effects. PMID:25762894

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

    PubMed

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

    2001-08-01

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

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

    PubMed

    Rau, Thomas; Ziemniak, John; Poulsen, David

    2016-01-01

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

  3. Evidence for Shared Genetic Risk Between Methamphetamine-Induced Psychosis and Schizophrenia

    PubMed Central

    Ikeda, Masashi; Okahisa, Yuko; Aleksic, Branko; Won, Mujun; Kondo, Naoki; Naruse, Nobuya; Aoyama-Uehara, Kumi; Sora, Ichiro; Iyo, Masaomi; Hashimoto, Ryota; Kawamura, Yoshiya; Nishida, Nao; Miyagawa, Taku; Takeda, Masatoshi; Sasaki, Tsukasa; Tokunaga, Katsushi; Ozaki, Norio; Ujike, Hiroshi; Iwata, Nakao

    2013-01-01

    Methamphetamine (METH) use can provoke psychotic reactions requiring immediate treatment, namely METH-induced psychosis. Although the distinction between METH-induced and primary psychosis is important for understanding their clinical courses, we do not have clear diagnostic procedure by their symptoms. Not only are there similarities between the clinical features of METH-induced psychosis and schizophrenia (SCZ), but there is also epidemiological evidence of a shared genetic risk between ‘METH-related' disorders and SCZ, which makes the differentiation of these two conditions difficult. In this study, we conducted a genome-wide association study (GWAS) targeting METH-dependent patients. The METH sample group, used in the METH-dependence GWAS, included 236 METH-dependent patients and 864 healthy controls. We also included a ‘within-case' comparison between 194 METH-induced psychosis patients and 42 METH-dependent patients without psychosis in a METH-induced psychosis GWAS. To investigate the shared genetic components between METH dependence, METH-induced psychosis, and SCZ, data from our previous SCZ GWAS (total N=1108) were re-analyzed. In the SNP-based analysis, none of the SNPs showed genome-wide significance in either data set. By performing a polygenic component analysis, however, we found that a large number of ‘risk' alleles for METH-induced psychosis are over-represented in individuals with SCZ (Pbest=0.0090). Conversely, we did not detect enrichment either between METH dependence and METH-induced psychosis or between METH dependence and SCZ. The results support previous epidemiological and neurobiological evidence for a relationship between METH-induced psychosis and SCZ. These also suggest that the overlap between genes scored as positive in these data sets can have higher probability as susceptibility genes for psychosis. PMID:23594818

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

    NASA Technical Reports Server (NTRS)

    Brown, Patricia A.; Comparin, Jeffrey H.

    1995-01-01

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

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

    PubMed Central

    El Ayadi, Amina; Zigmond, Michael J.

    2011-01-01

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

  6. Reward-related Brain Response and Craving Correlates of Marijuana Cue Exposure: A Preliminary Study in Treatment-Seeking Marijuana-Dependent Subjects

    PubMed Central

    Goldman, Marina; Szucs-Reed, Regina P.; Jagannathan, Kanchana; Ehrman, Ronald N.; Wang, Ze; Li, Yin; Suh, Jesse J.; Kampman, Kyle; O’Brien, Charles P.; Childress, Anna Rose; Franklin, Teresa R.

    2012-01-01

    Objective Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry [e.g., amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex (OFC)] triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain’s response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. Methods Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, BOLD functional MRI data were acquired during exposure to alternating 20 second blocks of marijuana-related versus matched nondrug visual cues. Results Brain activation during marijuana cue exposure was significantly greater in bilateral amygdala and hippocampus. Significant positive correlations between craving scores and brain activation were found in ventral striatum, and medial and lateral OFC (p<0.0001). Conclusions This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving, and extends the current literature on marijuana cue reactivity. Further, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances. PMID:23188041

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2011-08-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed

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

    1997-04-18

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

  13. Acute exposure to methamphetamine alters TLR9-mediated cytokine expression in human macrophage.

    PubMed

    Burns, Ariel; Ciborowski, Pawel

    2016-02-01

    Recent studies show that methamphetamine (Meth) use leads to higher susceptibility to and progression of infections, which suggests impairment of the immune system. The first line of defense against infections is the innate immune system and the macrophage is a key player in preventing and fighting infections. So we profiled cytokines over time in Meth treated THP-1 cells, as a human macrophage model, at a relevant concentration using high throughput screening to find a signaling target. We showed that after a single exposure, the effect of Meth on macrophage cytokine production was rapid and time dependent and shifted the balance of expression of cytokines to pro-inflammatory. Our results were analogous to previous reports in that Meth up-regulates TNF-α and IL-8 after two hours of exposure. However, global screening led to the novel identification of CXCL16, CXCL1 and many other up-regulated cytokines. We also showed CCL7 as the most down-regulated chemokine due to Meth exposure, which led us to hypothesize that Meth dysregulates the MyD88-dependent Toll-like receptor 9 (TLR9) signaling pathway. In conclusion, altered cytokine expression in macrophages suggests it could lead to a suppressed innate immunity in people who use Meth. PMID:26387832

  14. Current research on the epidemiology, medical and psychiatric effects, and treatment of methamphetamine use

    PubMed Central

    Rawson, Richard A.

    2014-01-01

    Methamphetamine (MA) is a drug that is widely used in many parts of the world. It has multiple neurobiological impacts on the nervous system, some of which are transitory and some more long lasting. MA activates the reward system of the brain and produces effects that are highly reinforcing, which can lead to abuse and dependence. Routes of administration that produce rapid onset of the drug’s effects (i.e., smoking and injection) are likely to lead to more rapid addiction and more medical and psychiatric effects. The medical effects of MA use are extensive, and chronic use of MA can produce significant neurological damage as well as damage to cardiovascular, pulmonary, and other organ systems. Both acute and chronic MA use can lead to extreme paranoia, anxiety, and depression, and following discontinuation of MA use, cognitive deficits and anhedonia can persist for months. No effective pharmacotherapies have been developed for the treatment of MA dependence, although this is an area of very active research. Several behavioral treatments have been shown to reduce MA use, but better treatments are needed. The research agenda for MA is substantial, with development of effective pharmacotherapies as one of the most important priorities. PMID:25214749

  15. Microstructural changes to the brain of mice after methamphetamine exposure as identified with diffusion tensor imaging.

    PubMed

    McKenna, Benjamin S; Brown, Gregory G; Archibald, Sarah; Scadeng, Miriam; Bussell, Robert; Kesby, James P; Markou, Athina; Soontornniyomkij, Virawudh; Achim, Cristian; Semenova, Svetlana

    2016-03-30

    Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH-dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location. PMID:27000304

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

    PubMed Central

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

    2015-01-01

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

  17. Current Research on Methamphetamine: Epidemiology, Medical and Psychiatric Effects, Treatment, and Harm Reduction Efforts

    PubMed Central

    Radfar, Seyed Ramin; Rawson, Richard A.

    2014-01-01

    Background Methamphetamine (MA) which is known as “shisheh” in Iran is a drug that widely is used in many parts of the world and it is near to a decade that is available for the most drug users and has a considerable prevalence of use. Due to high abuse prevalence and very new challenging phenomenon, it is very important that researchers and treatment providers become more familiar with different aspects of MA. Discussion It has multiple neurobiological impacts on the nervous system, some of which are transitory and some longer lasting. MA activates the reward system of the brain and produces effects that are highly reinforcing, which can lead to abuse and dependence. Routes of administration that produce rapid onset of the drug’s effects (i.e., smoking and injection) are likely to lead to more rapid addiction and more medical and psychiatric effects. No effective pharmacotherapies have been developed for the treatment of MA dependence; although, this is an area of very active research. Several behavioral treatments have been shown to reduce MA use, but better treatments are needed. Conclusion Harm reduction strategies for non-treatment seeking MA users are needed to reduce the risk of human immunodeficiency virus and other medical risks. The research agenda for MA is substantial, with development of effective pharmacotherapies as one of the most important priorities. Appropriate and effective response for prevention, treatment and harm reduction services due to increasing problems regarding MA in Iran and some other countries in the region. PMID:25984282

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  20. Allelic and genotypic associations of DRD2 TaqI A polymorphism with heroin dependence in Spanish subjects: a case control study

    PubMed Central

    Perez de los Cobos, Jose; Baiget, Montserrat; Trujols, Joan; Sinol, Nuria; Volpini, Victor; Banuls, Enrique; Calafell, Francesc; Luquero, Elena; del Rio, Elisabeth; Alvarez, Enric

    2007-01-01

    Background Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism. Methods We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females). Results The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70). Conclusion Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males. PMID:17543096

  1. Methamphetamine-using felons: Psychosocial and behavioral characteristics

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Itzhak, Yossef; Achat-Mendes, Cindy

    2004-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  5. The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats.

    PubMed

    Zhu, Rui; Yang, Tianjiao; Kobeissy, Firas; Mouhieddine, Tarek H; Raad, Mohamad; Nokkari, Amaly; Gold, Mark S; Wang, Kevin K; Mechref, Yehia

    2016-01-01

    Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb) underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis. PMID:27082425

  6. THE FIRST INJECTION EVENT: DIFFERENCES AMONG HEROIN, METHAMPHETAMINE, COCAINE, AND KETAMINE INITIATES

    PubMed Central

    Lankenau, Stephen E.; Wagner, Karla D.; Jackson Bloom, Jennifer; Sanders, Bill; Hathazi, Dodi; Shin, Charles

    2011-01-01

    This article describes how the drug type injected at the first injection event is related to characteristics of the initiate, risk behaviors at initiation, and future drug-using trajectories. A diverse sample (n=222) of young injection drug users (IDUs) were recruited from public settings in New York, New Orleans, and Los Angeles during 2004 and 2005. The sample was between 16 and 29 years old, and had injected ketamine at least once in the preceding two years. Interview data was analyzed both quantitatively and qualitatively. Young IDUs initiated with four primary drug types: heroin (48.6%), methamphetamine (20.3%), ketamine (17.1%), and cocaine (14%). Several variables evidenced statistically significant relationships with drug type: age at injection initiation, level of education, region of initiation, setting, mode of administration, patterns of self-injection, number of drugs ever injected, current housing status, and their hepatitis C virus (HCV) status. Qualitative analyses revealed that rationale for injection initiation and subjective experiences at first injection differed by drug type. PMID:21423792

  7. The Effect of Chronic Methamphetamine Exposure on the Hippocampal and Olfactory Bulb Neuroproteomes of Rats

    PubMed Central

    Zhu, Rui; Yang, Tianjiao; Kobeissy, Firas; Mouhieddine, Tarek H.; Raad, Mohamad; Nokkari, Amaly; Gold, Mark S.; Wang, Kevin K.; Mechref, Yehia

    2016-01-01

    Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb) underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis. PMID:27082425

  8. Distributed attentional deficits in chronic methamphetamine abusers: Evidence from the Attentional Network Task (ANT)

    PubMed Central

    Salo, Ruth; Gabay, Shai; Fassbender, Catherine; Henik, Avishai

    2016-01-01

    Objective The goal of the present study was to examine distributed attentional functions in long-term but currently abstinent methamphetamine (MA) abusers using a task that measures attentional alertness, orienting, and conflict resolution. Methods Thirty currently abstinent MA abusers (1 month–5 years) and 22 healthy non-substance using adults were administered a multimodal version of the Attentional Network Task (ANT-I). In this task subjects identified the direction of a centrally presented arrow using a key press. Analyses examined the interaction between alerting tones, location cueing and congruency between the target arrows and flanking distractor stimuli. Results All participants were faster when an auditory tone preceded the trial onset (p < 0.001), on trials in which a valid cue preceded the location of the target arrow (p < 0.001), and on congruent trials (i.e., when all display arrows faced in the same direction) (p < 0.001). Of primary interest was the finding that MA abusers were more influenced by the conflict between the peripheral arrows and the central target arrow (p = 0.009). There were also correlations between length of drug sobriety and executive function as well as between drug-induced psychiatric symptoms and alertness. Conclusions These results suggest that chronic MA abusers display cognitive deficits that may reflect a specific vulnerability to distraction on a task of executive function. These findings are consistent with other studies that have reported deficits in anterior attentional systems and top-down cognitive control. PMID:21906864

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

    PubMed

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

    2009-04-01

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

  10. Racial disparities in methamphetamine-associated intracerebral hemorrhage

    PubMed Central

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

    2015-01-01

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

  11. Association analysis of GABA receptor subunit genes on 5q33 with heroin dependence in a Chinese male population.

    PubMed

    Loh, E W; Tang, N L S; Lee, D T S; Liu, S I; Stadlin, Alfreda

    2007-06-01

    GABAA receptor subunit genes clustered on 5q33 play a role in the development of alcoholism and methamphetamine use disorder without psychosis. The present study explored the possible contribution of the same subunit genes to the development of heroin dependence. Single nucleotide polymorphisms (SNPs) of the GABAA receptor subunits GABRB2, GABRA6, GABRA1, and GABRG2 were examined in 178 male Han Chinese heroin-dependent and 170 male control subjects. A significant difference in allele frequency for the SNP rs211014 in the GABAAgamma2 receptor subunit gene between cases and controls was identified (P = 0.015). A possible mechanism for the involvement of the GABA receptor subunit genes on 5q33 in the development of heroin dependence is discussed. PMID:17440936

  12. Time of day influences the voluntary intake and behavioral response to methamphetamine and food reward.

    PubMed

    Keith, Diana R; Hart, Carl L; Robotham, Margaret; Tariq, Maliha; Le Sauter, Joseph; Silver, Rae

    2013-09-01

    The circadian timing system influences a vast array of behavioral responses. Substantial evidence indicates a role for the circadian system in regulating reward processing. Here we explore time of day effects on drug anticipation, locomotor activity, and voluntary methamphetamine (MA) and food intake in animals with ad libitum food access. We compared responses to drug versus a palatable treat during their normal sleep times in early day (zeitgeber time (ZT) 0400) or late day (ZT 1000). In the first study, using a between-subjects design, mice were given daily 1-h access to either peanut butter (PB-Alone) or to a low or high concentration of MA mixed in PB (MA+PB). In study 2, we repeated the experiment using a within-subjects design in which mice could choose between PB-Alone and MA+PB at either ZT 0400 or 1000. In study 3, the effects of MA-alone were investigated by evaluating anticipatory activity preceding exposure to nebulized MA at ZT 0400 vs. ZT 1000. Time of day effects were observed for both drug and palatable treat, such that in the between groups design, animals showed greater intake, anticipatory activity, and post-ingestional activity in the early day. Furthermore, there were differences among mice in the amount of MA ingested but individuals were self-consistent in their daily intake. The results for the within-subjects experiment also revealed robust individual differences in preference for MA+PB or PB-Alone. Interestingly, time of day effects on intake were observed only for the preferred substance. Anticipatory activity preceding administration of MA by nebulization was also greater at ZT 0400 than ZT 1000. Finally, pharmacokinetic response to MA administered intraperitoneally did not vary as a function of time of administration. The results indicate that time of day is an important variable mediating the voluntary intake and behavioral effects of reinforcers. PMID:23711589

  13. Methamphetamine and amphetamine concentrations in survivors of body-packer syndrome in Japan.

    PubMed

    Uekusa, Kyoko; Hayashida, Makiko; Saito, Nobuyuki; Mashiko, Kunihiro; Hara, Kenji; Waters, Brian; Ohno, Youkichi

    2013-04-10

    There are few reports from Japan on the analysis of fluids in survivors of body-packer syndrome. We analyzed the concentrations of stimulants in the serum, plasma and urine collected from three patients suspected of being body packers at immigration that were referred to hospitals between 2010 and 2011. The drugs were extracted with solid-phase columns and analyzed by gas chromatography-mass spectrometry (GC-MS). In all cases, wrapped, cylindrical packets of foreign bodies were detected in the intestinal tract on plain X-ray (X-P) and computed tomography (CT), and they were eventually removed surgically. In case 1, the patient presented with convulsions and tachycardia at admission to the hospital and one of the packets was found to have ruptured. In case 2, although the subject appeared to have an intestinal obstruction caused by the packets on the third day, he exhibited no symptoms on arrival and the packets did not appear to have ruptured. In case 3, the patient exhibited restlessness on the first day and one of the removed packets had ruptured. In all cases, methamphetamine (MA) and amphetamine (AP) were detected in serum, plasma and urine. In this study, we report the variation in MA and AP concentrations in survivors of body-packer syndrome. The serum and plasma concentrations of MA were high in subjects that exhibited symptoms of MA intoxication. MA and AP were also detected in the case in which the patient exhibited no symptoms of intoxication and the packets had not ruptured. These results suggest either that the stimulants may have seeped through the wrap of the packets, or that the subject had been abusing the drugs. PMID:23116635

  14. First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.

    PubMed

    Stevens, Misty W; Henry, Ralph L; Owens, S Michael; Schutz, Ralph; Gentry, W Brooks

    2014-01-01

    This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17-19 d in the 3 highest dose groups and volume of distribution of 5-6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration. PMID:25484042

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Mithramycin protects against dopaminergic neurotoxicity in the mouse brain after administration of methamphetamine.

    PubMed

    Hagiwara, Hiroko; Iyo, Masaomi; Hashimoto, Kenji

    2009-12-01

    The present study was undertaken to examine the effects of mithramycin, an inhibitor of transcription factor Specificity protein (Sp)-1, on the behavioral changes and dopaminergic neurotoxicity in the mouse striatum after administration of methamphetamine (METH). Pretreatment with mithramycin (75, 150 or 300 microg/kg) did not alter acute hyperlocomotion in mice after a single administration of METH (3 mg/kg). However, the development of behavioral sensitization in mice after repeated administration of METH (3 mg/kg/day, once daily for 5 days) was significantly blocked by pretreatment with mithramycin (300 microg/kg). Furthermore, pretreatment with mithramycin (300 microg/kg) significantly attenuated the hyperthermia in mice after repeated administration of METH (3 mg/kgx3, 3-h intervals). Moreover, the combination of pretreatment and subsequent administration of mithramycin (75, 150 or 300 microg/kg) significantly attenuated the reductions of dopamine (DA), its major metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and DA transporter (DAT) in the striatum after repeated administration of METH (3 mg/kgx3, 3-h intervals), and these attenuations were dose dependent. These findings suggest that mithramycin attenuates the development of behavioral sensitization and dopaminergic neurotoxicity in mice after repeated administration of METH. Therefore, mithramycin could have potential for the treatment of METH abusers, particularly since this drug has been approved by the Food and Drug Administration in the United States. In the future, however, another Sp1 inhibitors with fewer side effects might be more appropriate. PMID:19748494

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

    PubMed

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

    2015-08-01

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

  20. Effect of methamphetamine on the microglial damage: role of potassium channel Kv1.3.

    PubMed

    Wang, Jun; Qian, Wenyi; Liu, Jingli; Zhao, Jingjing; Yu, Pan; Jiang, Lei; Zhou, Jing; Gao, Rong; Xiao, Hang

    2014-01-01

    Methamphetamine (Meth) abusing represents a major public health problem worldwide. Meth has long been known to induce neurotoxicity. However, the mechanism is still remained poorly understood. Growing evidences indicated that the voltage-gated potassium channels (Kv) were participated in neuronal damage and microglia function. With the whole cell patch clamp, we found that Meth significantly increased the outward K⁺ currents, therefore, we explored whether Kv1.3, one of the major K⁺ channels expressed in microglia, was involved in Meth-induced microglia damage. Our study showed that Meth significantly increased the cell viability in a dose dependent manner, while the Kv blocker, tetraethylamine (TEA), 4-Aminopyridine (4-AP) and Kv1.3 specific antagonist margatoxin (MgTx), prevented against the damage mediated by Meth. Interestingly, treatment of cells with Meth resulted in increasing expression of Kv1.3 rather than Kv1.5, at both mRNA and protein level, which is partially blocked by MgTx. Furthermore, Meth also stimulated a significant increased expression of IL-6 and TNF-α at protein level, which was significantly inhibited by MgTx. Taken together, these results demonstrated that Kv1.3 was involved in Meth-mediated microglial damage, providing the potential target for the development of therapeutic strategies for Meth abuse. PMID:24533129

  1. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ

    PubMed Central

    Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F.; Kanthasamy, Anumantha G.; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2014-01-01

    This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (–/–) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (–/–) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (–/–) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. PMID:22512859

  2. Methamphetamine alters occludin expression via NADPH oxidase-induced oxidative insult and intact caveolae

    PubMed Central

    Park, Minseon; Hennig, Bernhard; Toborek, Michal

    2012-01-01

    Abstract Methamphetamine (METH) is a drug of abuse with neurotoxic and vascular effects that may be mediated by reactive oxygen species (ROS). However, potential sources of METH-induced generation of ROS are not fully understood. This study is focused on the role of NAD(P)H oxidase (NOX) in METH-induced dysfunction of brain endothelial cells. Treatment with METH induced a time-dependent increase in phosphorylation of NOX subunit p47, followed by its binding with gp91 and p22, and the formation of an active NOX complex. An increase in NOX activity was associated with elevated production of ROS, alterations of occludin levels and increased transendothelial migration of monocytes. Inhibition of NOX by NSC 23766 attenuated METH-induced ROS generation, changes in occludin protein levels and monocyte migration. Because an active NOX complex is localized to caveolae, we next evaluated the role of caveolae in METH-mediated toxicity to brain endothelial cells. Treatment with METH induced phosphorylation of ERK1/2 and caveolin-1 protein. Inhibition of ERK1/2 activity or caveolin-1 silencing protected against METH-induced alterations of occludin levels. These findings indicate an important role of NOX and functional caveolae in METH-induced oxidative stress in brain endothelial cells that contribute to the subsequent alterations of occludin levels and transendothelial migration of inflammatory cells. PMID:21435178

  3. Methamphetamine exposure during early postnatal development in rats: I. Acoustic startle augmentation and spatial learning deficits.

    PubMed

    Vorhees, C V; Ahrens, K G; Acuff-Smith, K D; Schilling, M A; Fisher, J E

    1994-04-01

    Methamphetamine (MA) induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received less attention. In this experiment the effects of MA exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously with d-MA (30 mg/kg b.i.d.) early in postnatal development (days 1-10), later (postnatal days 11-20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited augmented acoustic startle and impaired performance in a complex multiple-T water maze. Only the early MA exposure group showed a persistent deficit in weight while only the later MA exposure group showed impaired learning in the Morris hidden platform maze. Effects on locomoter activity are reported in the accompanying article. It was concluded that the effects of MA are both long lasting and stage dependent and involve cognitive as well as arousal functions. PMID:7855197

  4. Predictors of Relapse and Dropout During a 12-Week Relapse Prevention Program for Methamphetamine Users.

    PubMed

    Chen, Yi-Chih; Chen, Chih-Ken; Wang, Liang-Jen

    2015-01-01

    In this research, the possible neuropsychological predictors of relapse and dropout of group cognitive behavioral therapy (CBT) for methamphetamine (MA) users were explored. Participants were 42 MA users sentenced by the judicial system to take part in an out-patient relapse prevention program for MA abuse and dependence that employs a CBT model once a week over the course of 12 weeks. Baseline neuropsychological functions were evaluated with the Conners' Continuous Performance Test, Wisconsin Card Sorting Test, Iowa Gambling Task, and Barratt Impulsiveness Scale. All participants had to submit to urine drug tests every week. Of the 42 participants, 69.0% had a MA positive urine screening result at least once throughout the program (relapse), while 40.5% dropped out of the treatment program prior to its completion. Short duration of MA abstinence at baseline and poor attention predicted relapse. Predictors of dropout included being unmarried and having risky decision making. Findings may be helpful for clinicians, who can screen for the aforementioned risk factors and provide strategies for high-risk patients to help prevent relapse and dropout among MA users in treatment programs. PMID:26267045

  5. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

    PubMed Central

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

    2015-01-01

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

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

    PubMed Central

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

    2015-01-01

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

  7. Acute Methamphetamine Intoxication: Brain Hyperthermia, Blood-Brain Barrier and Brain Edema

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2011-01-01

    Methamphetamine (METH) is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-induced metabolic activation (or oxidative stress) are primary factors underlying damage of neural cells, in this work we will present data suggesting a role of brain hyperthermia and associated leakage of the brain-blood barrier (BBB) in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial activation, and increased water content (edema), which are related to drug-induced brain hyperthermia. Third, we document widespread morphological abnormalities of brain cells, including neurons, glia, epithelial and endothelial cells developing rapidly during acute METH intoxication. These structural abnormalities are tightly related to the extent of brain hyperthermia, leakage of the BBB, and brain edema. While it is unclear whether these rapidly developed morphological abnormalities are reversible, this study demonstrates that METH induces multiple functional and structural perturbations in the brain, determining its acute toxicity and possibly contributing to neurotoxicity. PMID:19897075

  8. The rewarding properties of methamphetamine in an invertebrate model of drug addiction.

    PubMed

    Imeh-Nathaniel, Adebobola; Adedeji, Adekunle; Huber, Robert; Nathaniel, Thomas I

    2016-01-01

    The rewarding properties of drugs in the mammalian system depend on their ability to activate appetitive motivational states. The associated underlying mechanism is strongly conserved in evolution and invertebrates have recently emerged as a powerful new model in addiction research. The natural reward system in crayfish has surprisingly proven sensitive to human drugs of abuse, providing a new model for research into the basic biological mechanisms of drug addiction. In this study, we examined the presence of natural reward systems in crayfish, and then characterized its sensitivity to 2.5 μg/g, 5.0 μg/g and 10.0 μg/g doses of methamphetamine (METH). Using the conditioned place preference (CPP) paradigm, we demonstrated that irrespective of the number of doses of METH injected into the pericardial system, crayfish seek out a particular tactile environment that had previously been paired with the METH. This study demonstrates that crayfish offer a comparative and complementary approach in addiction research. It contributes an evolutionary context to our understanding of a key component in learning and of natural reward as an important life-sustaining process. PMID:26477734

  9. Skin vasoreactivity to insulin iontophoresis is reduced in elderly subjects and is absent in treated non-insulin-dependent diabetes patients.

    PubMed

    Rossi, Marco; Cupisti, Adamasco; Ricco, Roberto; Santoro, Gino; Pentimone, Ferdinando; Carpi, Angelo

    2004-12-01

    We investigated the skin vasoreactivity to insulin in normal subjects and in treated non-insulin-dependent diabetes mellitus (NIDDM) patients. We measured cutaneous perfusion by laser-Doppler flowmetry (LDF) at rest and during skin cathodal iontophoresis (six pulses of 0.1 mA each for 20 s, with 40 s interval between stimulations) of insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with of 0.9% saline solution) in 45 healthy subjects (HS), (25 males, 20 females, aged 45 +/- 18 years), and in 15 treated NIDDM patients (13 males), aged 66 +/- 8 years. Fifteen of the HS were used as controls. In these 15 sex- and age-matched HS and in the patients, we assessed also the skin postischemic hyperemia by LDF. In HS cutaneous blood flux response (CBF) to iontophoresis of insulin in saline (expressed as percent changes from baseline) was significantly higher than CBF response to iontophoresis of pure saline (maximum response: 360 +/- 51% versus 172 +/- 42%, respecti