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Sample records for methamphetamine dependent subjects

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

    PubMed

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

    2012-05-01

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

  2. Withdrawal symptoms in abstinent methamphetamine-dependent subjects.

    PubMed

    Zorick, Todd; Nestor, Liam; Miotto, Karen; Sugar, Catherine; Hellemann, Gerhard; Scanlon, Graham; Rawson, Richard; London, Edythe D

    2010-10-01

    Withdrawal symptoms have been linked to a propensity for relapse to drug abuse. Inasmuch as this association applies to methamphetamine (MA) abuse, an understanding of the course of MA withdrawal symptoms may help to direct treatment for MA dependence. Previous studies of symptoms manifested during abstinence from MA have been limited in size and scope. We asked (i) whether debilitating psychological and/or physical symptoms appear during the first several weeks of MA abstinence, (ii) how craving for MA evolves and (iii) whether psychiatric symptoms (e.g. depression, psychosis) persist beyond a month of abstinence. A study of MA-dependent participants, who initiated and maintained abstinence from the drug for up to 5 weeks, compared to a matched healthy comparison group. In-patient research hospital ward (MA-dependent subjects) and out-patient (comparison subjects). Fifty-six MA-dependent and eighty-nine comparison subjects. Rater-assessed MA withdrawal questionnaire and self-report assessment of craving (MA-dependent subjects) and self-report assessment of psychiatric symptoms (both groups). At study entry, MA-dependent subjects exhibited a wide range in severity of depressive symptoms, with the average score at a mild-moderate level of severity. Symptoms of psychosis were also prevalent. While depressive and psychotic symptoms largely resolved within a week of abstinence, craving did not decrease significantly from the time of initiating abstinence until the second week, and then continued at a reduced level to the fifth week. Depressive and psychotic symptoms accompany acute withdrawal from methamphetamine but resolve within 1 week. Craving is also present and lasts at least 5 weeks. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

  3. Withdrawal symptoms in abstinent methamphetamine-dependent subjects

    PubMed Central

    Zorick, Todd; Nestor, Liam; Miotto, Karen; Sugar, Catherine; Hellemann, Gerhard; Scanlon, Graham; Rawson, Richard; London, Edythe D.

    2011-01-01

    Aims Withdrawal symptoms have been linked to a propensity for relapse to drug abuse. Inasmuch as this association applies to methamphetamine (MA) abuse, an understanding of the course of MA withdrawal symptoms may help to direct treatment for MA dependence. Previous studies of symptoms manifested during abstinence from MA have been limited in size and scope. We asked (i) whether debilitating psychological and/or physical symptoms appear during the first several weeks of MA abstinence, (ii) how craving for MA evolves and (iii) whether psychiatric symptoms (e.g. depression, psychosis) persist beyond a month of abstinence. Design A study of MA-dependent participants, who initiated and maintained abstinence from the drug for up to 5 weeks, compared to a matched healthy comparison group. Setting In-patient research hospital ward (MA-dependent subjects) and out-patient (comparison subjects). Participants Fifty-six MA-dependent and eighty-nine comparison subjects. Measurements Rater-assessed MA withdrawal questionnaire and self-report assessment of craving (MA-dependent subjects) and self-report assessment of psychiatric symptoms (both groups). Findings At study entry, MA-dependent subjects exhibited a wide range in severity of depressive symptoms, with the average score at a mild–moderate level of severity. Symptoms of psychosis were also prevalent. While depressive and psychotic symptoms largely resolved within a week of abstinence, craving did not decrease significantly from the time of initiating abstinence until the second week, and then continued at a reduced level to the fifth week. Conclusions Depressive and psychotic symptoms accompany acute withdrawal from methamphetamine but resolve within 1 week. Craving is also present and lasts at least 5 weeks. PMID:20840201

  4. Findings of preserved implicit attention in methamphetamine dependent subjects.

    PubMed

    Salo, Ruth; Leamon, Martin H; Natsuaki, Yutaka; Moore, Charles; Waters, Christy; Nordahl, Thomas E

    2008-01-01

    Long-term methamphetamine (MA) abuse is associated with a wide range of deficits on explicit tasks of selective attention. Less is known however about the effects of MA abuse on implicit measures of attention. Accordingly, we used a computerized spatial priming task to assess implicit attentional processes in 54 MA dependent subjects (mean age=37.04+/-8.9 years) and 32 healthy controls without history of any form of substance abuse (mean age=33.63+/-7.05 years). The MA dependent subjects had been drug-abstinent a minimum of 3 weeks with a mean duration of MA use of 13.27+/-7.75 years. The MA dependent subjects did not differ significantly from controls on either inhibitory priming [p=.37] or facilitory priming) [p=.69]. This result comports with our earlier findings of intact object-based priming in MA dependent individuals and suggests that intact priming effects extend across spatial domains. Further, this pattern of sparing suggests that cortical brain systems typically supporting implicit attentional functioning are relatively intact in long-term MA dependent individuals whereas brain systems supporting explicit attentional processes are affected.

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. 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

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

    PubMed

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

    2010-01-15

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

  9. Comparison of Wisconsin Card Sorting Test results between Czech subjects dependent on methamphetamine versus healthy volunteers.

    PubMed

    Hosak, Ladislav; Preiss, Marek; Bazant, Jan; Tibenska, Andrea; Cermakova, Radka; Cermakova, Eva

    2012-06-01

    Methamphetamine is a neurotoxic agent. Its chronic abuse may result in cognitive impairment with negative consequences for patients' treatment and rehabilitation. The aim of the study was to compare Wisconsin Card Sorting Test profiles of Czech subjects dependent on methamphetamine with healthy individuals. Forty-three hospitalized Czech Caucasian patients including twenty-seven men at the average age of 25.3±5.2 years dependent on methamphetamine for 6.2±3.3 years were assessed by the Wisconsin Card Sorting Test. We used the same neurocognitive test for the comparison group of healthy controls with the same ethnicity (N=52, men N=28, average age of 38.7±12.1 years). We applied the Chi-Square Test, Two-Sample T Test, Mann-Whitney U Test and Kolmogorov-Smirnov Test to compare methamphetamine dependent patients with healthy volunteers. All recorded Wisconsin Card Sorting Test parameters were significantly different in the group of methamphetamine dependent patients versus healthy volunteers (P=0.04-0.006; Mann-Whitney U Test, Two-Sample T Test). The results showed a higher error rate and a smaller achievement quality in the patients as against healthy subjects. We ascertained a significant cognitive deterioration in the patients as compared to healthy volunteers even if the average patients' achievements were in the normal range according to the test norms. A cognitive impairment was present in the group of patients as compared to healthy controls. Better understanding of neurocognitive symptoms in methamphetamine dependent subjects should help to generate modern therapeutic approaches, both pharmacological and psychosocial, to prevent or attenuate the long-term negative consequences of methamphetamine use disorders.

  10. Determinants of cue-elicited craving and physiologic reactivity in methamphetamine-dependent subjects in the laboratory.

    PubMed

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

    2010-03-01

    Craving for methamphetamine is commonly reported by heavy users of the drug and may increase the risk of relapse in newly abstinent individuals. Exposure to methamphetamine-associated cues in the laboratory can elicit measureable craving and autonomic reactivity in some individuals with methamphetamine dependence. In this study, clinical and demographic correlates of methamphetamine craving and the optimal conditions for its measurement in the laboratory are explored. Subjective (craving) and physiologic (heart rate and skin conductance) reactivity to presentation of methamphetamine-associated photo, video, and paraphernalia cues were evaluated in 43 subjects with methamphetamine dependence. Association of cue reactivity with demographic and clinical characteristics including duration, frequency, amount, and recency of methamphetamine use were assessed. Craving was reported by fewer than half of subjects at baseline and by approximately 70% of subjects after methamphetamine cue exposure. Relative to baseline, subjective craving was increased by all three cue modalities to a similar extent. In general, physiological cue reactivity correlated poorly with cue-induced craving. Craving at baseline was strongly predictive of cue-induced craving. Differences in cue-induced craving were not associated with age, sex, education, employment, treatment status, or number of days using methamphetamine in the 60 days prior to study entry. In contrast, the degree of baseline craving was strongly associated with employment status and the number of days using methamphetamine in the past 60 days. Cue-induced craving for methamphetamine may be reliably measured in methamphetamine-dependent individuals in the laboratory. Further studies employing the cue reactivity paradigm in methamphetamine dependence are warranted.

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

    PubMed

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

    2015-01-01

    A high prevalence of tobacco smoking has been observed in methamphetamine users, but there have been no in vivo brain neurochemistry studies addressing gender effects of tobacco smoking in methamphetamine users. Methamphetamine addiction is associated with increased risk of depression and anxiety in females. There is increasing evidence that selective analogues of nicotine, a principal active component of tobacco smoking, may ease depression and improve cognitive performance in animals and humans. To investigate the effects of tobacco smoking and gender on brain phosphocreatine (PCr) levels, a marker of brain energy metabolism reported to be reduced in methamphetamine-dependent subjects. Thirty female and 27 male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. Analysis of covariance revealed that there were statistically significant slope (PCr versus lifetime amount of tobacco smoking) differences between female and male methamphetamine-dependent subjects (p = 0.03). In females, there was also a statistically significant interaction between lifetime amounts of tobacco smoking and methamphetamine in regard to PCr levels (p = 0.01), which suggests that tobacco smoking may have a more significant positive impact on brain PCr levels in heavy, as opposed to light to moderate, methamphetamine-dependent females. These results indicate that tobacco smoking has gender-specific effects in terms of increased anterior cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette smoking in methamphetamine-dependent women, particularly those with heavy methamphetamine use, may have a potentially protective effect upon neuronal metabolism.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

    Galloway, Gantt P; Didier, Ryne; Garrison, Kathleen; Mendelson, John

    2008-01-01

    Background Predictors of relapse to methamphetamine use are poorly understood. State variables may play an important role in relapse, but they have been difficult to measure at frequent intervals in outpatients. Methods We conducted a feasibility study of the use of cellular telephones to collect state variable data from outpatients. Six subjects in treatment for methamphetamine dependence were called three times per weekday for approximately seven weeks. Seven questionnaires were administered that assessed craving, stress, affect and current type of location and social environment. Results 395/606 (65%) of calls attempted were completed. The mean time to complete each call was 4.9 (s.d. 1.8) minutes and the mean time to complete each item was 8.4 (s.d. 4.8) seconds. Subjects rated the acceptability of the procedures as good. All six cellular phones and battery chargers were returned undamaged. Conclusion Cellular telephones are a feasible method for collecting state data from methamphetamine dependent outpatients. PMID:19997532

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

    PubMed

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

    2005-02-01

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

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

    PubMed

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

    2014-01-01

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

  16. Physiological and subjective effects of acute intranasal methamphetamine during atomoxetine maintenance.

    PubMed

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

    2011-11-01

    Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed. This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients. After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min. Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance. These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Physiological and Subjective Effects of Acute Intranasal Methamphetamine During Atomoxetine Maintenance

    PubMed Central

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

    2011-01-01

    Rationale Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed. Objectives This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients Methods After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 minutes. Results Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance. Conclusions These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined. PMID:21802442

  18. Management of methamphetamine abuse and dependence.

    PubMed

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

    2006-10-01

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

  19. Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects.

    PubMed

    Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima; Wallace, Christopher; Wells, Lynda; Dawes, Michael; Wang, Yanmei

    2005-06-01

    In healthy human volunteers, we have previously shown that isradipine, a dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine-induced positive subjective effects associated with its abuse liability, presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present study, we combined acute immediate-release (IR) isradipine with repeated sustained-release (SR) isradipine pretreatment to determine whether isradipine could antagonize methamphetamine's positive subjective and reinforcing effects in methamphetamine-dependent research subjects. We included 18 non-treatment-seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this double-blind, within-subject, cross-over study, which was done in a human laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on three different days after 5 days of double-blind cross-over treatment with either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self-report questionnaires measured drug liking, euphoria, craving, stimulation, and methamphetamine preference. Methamphetamine reinforcement was measured by a behavioural procedure involving choices between methamphetamine and money. For those who received isradipine second and placebo first as the pretreatment paradigm but not vice versa, methamphetamine-induced drug liking, elation, and preference were reduced significantly by isradipine. Depending upon conditioning status, isradipine can reduce some methamphetamine-induced positive subjective and reinforcing effects associated with its abuse liability in methamphetamine addicts.

  20. 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

  1. Acute modafinil effects on attention and inhibitory control in methamphetamine-dependent humans.

    PubMed

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

    2011-11-01

    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. 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. 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. 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.

  2. Subjective and physiological effects of acute intranasal methamphetamine during d-amphetamine maintenance.

    PubMed

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

    2011-04-01

    Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence, suggesting other strategies like pharmacotherapy are needed. This experiment determined the subjective and physiological effects of intranasal methamphetamine during D: -amphetamine maintenance in eight non-treatment-seeking stimulant-dependent participants. We predicted D: -amphetamine maintenance would attenuate the acute subjective effects of intranasal methamphetamine. We also predicted intranasal methamphetamine would be well tolerated during D: -amphetamine maintenance. After at least 7 days of maintenance on sustained-release D: -amphetamine (0 and 45 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 2.5, 5, 10, and 20 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min. Intranasal methamphetamine produced prototypical subjective and physiological effects (e.g., increased ratings of Like Drug; increased heart rate, blood pressure, and body temperature). The acute effects of intranasal methamphetamine were significantly diminished during D: -amphetamine maintenance relative to placebo maintenance. These results are concordant with those of clinical trials and provide further support for the use of agonist replacement therapy to manage methamphetamine dependence. Additional research in humans is needed to determine the effectiveness of D: -amphetamine under different experimental conditions that more closely reflect use in the natural environment (e.g., higher methamphetamine doses) and behavioral arrangements that are predictive of pharmacotherapy effectiveness (e.g., drug self-administration).

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

    PubMed

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

    2012-10-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2011-12-15

    Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABA(A) activity following chronic stimulant use, and that positive modulation of GABA(A) receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABA(A) modulators could be useful as pharmacotherapies for stimulant-use disorders. 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 1mg/day). 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. The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABA(A) 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 GABA(A) positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment. Copyright © 2011. Published by Elsevier Ireland Ltd.

  6. 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

  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. [Prevalence and Therapy of Crystal Methamphetamine Dependence].

    PubMed

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

    2017-02-01

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

  9. Effects of acute topiramate dosing on methamphetamine-induced subjective mood.

    PubMed

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

    2007-02-01

    Clinical studies have shown that topiramate, a sulphamate-substituted fructopyranose derivative, might be an efficacious treatment for alcohol dependence, smoking cessation within an alcohol-dependent population, and cocaine dependence. Mechanistically, topiramate's therapeutic effects have been hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the primary substrate that governs the acquisition, maintenance, and reinstatement of goal-directed behaviour towards seeking abused drugs. Predicated on this hypothesis, we tested in 10 methamphetamine-dependent individuals (three females) whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive subjective effects and reinforcement can be antagonized by low- or high-dose (100 or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial design. Methamphetamine administration was associated with orderly, prototypical, and significant increases on measures of stimulation, euphoria, craving, and reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone showed a non-significant trend towards mild reductions in positive mood and reinforcement; yet topiramate appeared to accentuate the appreciation of methamphetamine-induced stimulation and euphoria significantly, but not craving or reinforcement. The experimental combination of topiramate and methamphetamine appeared to be safe and well tolerated, with few adverse events. Acute dosing with up to 200 mg topiramate appears to enhance, rather than attenuate, the positive subjective effects of methamphetamine. Perhaps this indicates a partial inhibition of methamphetamine's reinforcing effects. Thus, testing chronically administered or higher doses, or both, of topiramate would be necessary to determine conclusively whether or not it can attenuate the positive subjective and reinforcing effects of methamphetamine.

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

    PubMed Central

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

    2010-01-01

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

  11. Methamphetamine

    MedlinePlus

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

  12. Association between quantitative EEG and neurocognition in methamphetamine-dependent volunteers.

    PubMed

    Newton, Thomas F; Kalechstein, Ari D; Hardy, David J; Cook, Ian A; Nestor, Liam; Ling, Walter; Leuchter, Andrew F

    2004-01-01

    Exposure to methamphetamine is associated with long-lasting reductions in markers for dopaminergic neurons in preclinical models and in humans. These changes may be associated with alterations in brain electrical activity and in cognition. The sample included 9 methamphetamine-dependent subjects and 10 non-drug-using volunteers. Methamphetamine-dependent subjects were hospitalized for 4 days to document abstinence; non-drug-using volunteers were studied as outpatients. EEGs were recorded in the eyes-closed resting state, and absolute EEG power in each frequency band (0.5-4 Hz, 4-8 Hz, 8-12 Hz, and 12-20 Hz) was measured using a fast Fourier transform. EEG power was log-transformed prior to analysis. Cognition was measured using computerized reaction time tasks. Within the methamphetamine-dependent group only, increased theta quantitative EEG (QEEG) power correlated significantly with reaction time on tasks that were more difficult or that were degraded by fatigue. Increased theta QEEG power also correlated with reduced accuracy on a working memory task. Increased QEEG power in the theta band is associated with worse performance on reaction time tasks in the methamphetamine-dependent sample but not in the non-drug-using volunteers. Methamphetamine dependence is associated with pathological alterations in brain electrical activity and in cognitive performance. QEEG appears to provide a sensitive measure of methamphetamine-associated alterations in brain function.

  13. Educational Attainment is not a Good Proxy for Cognitive Function in Methamphetamine Dependence

    PubMed Central

    Dean, Andy C.; Hellemann, Gerhard; Sugar, Catherine A.; London, Edythe D.

    2014-01-01

    We sought to test the hypothesis that methamphetamine use interferes with both the quantity and quality of one's education, such that the years of education obtained by methamphetamine dependent individuals serves to underestimate general cognitive functioning and overestimate the quality of academic learning. Thirty-six methamphetamine-dependent participants and 42 healthy comparison subjects completed cognitive tests and self-report measures in Los Angeles, California. An overall cognitive battery score was used to assess general cognition, and vocabulary knowledge was used as a proxy for the quality of academic learning. Linear regression procedures were used for analyses. Supporting the hypothesis that methamphetamine use interferes with the quantity of education, we found that a) earlier onset of methamphetamine use was associated with fewer years of education (p < .01); b) using a normative model developed in healthy participants, methamphetamine-dependent participants had lower educational attainment than predicted from their demographics and performance on the cognitive battery score (p < .01); and c) greater differences between methamphetamine-dependent participants' predicted and actual educational attainment were associated with an earlier onset of MA use (p ≤ .01). Supporting the hypothesis that methamphetamine use interferes with the quality of education, years of education received prior to the onset of methamphetamine use was a better predictor of a proxy for academic learning, vocabulary knowledge, than was the total years of education obtained. Results support the hypothesis that methamphetamine use interferes with the quantity and quality of educational exposure, leading to under- and overestimation of cognitive function and academic learning, respectively. PMID:22206606

  14. Educational attainment is not a good proxy for cognitive function in methamphetamine dependence.

    PubMed

    Dean, Andy C; Hellemann, Gerhard; Sugar, Catherine A; London, Edythe D

    2012-06-01

    We sought to test the hypothesis that methamphetamine use interferes with both the quantity and quality of one's education, such that the years of education obtained by methamphetamine dependent individuals serves to underestimate general cognitive functioning and overestimate the quality of academic learning. Thirty-six methamphetamine-dependent participants and 42 healthy comparison subjects completed cognitive tests and self-report measures in Los Angeles, California. An overall cognitive battery score was used to assess general cognition, and vocabulary knowledge was used as a proxy for the quality of academic learning. Linear regression procedures were used for analyses. Supporting the hypothesis that methamphetamine use interferes with the quantity of education, we found that (a) earlier onset of methamphetamine use was associated with fewer years of education (p<.01); (b) using a normative model developed in healthy participants, methamphetamine-dependent participants had lower educational attainment than predicted from their demographics and performance on the cognitive battery score (p<.01); and (c) greater differences between methamphetamine-dependent participants' predicted and actual educational attainment were associated with an earlier onset of MA use (p≤.01). Supporting the hypothesis that methamphetamine use interferes with the quality of education, years of education received prior to the onset of methamphetamine use was a better predictor of a proxy for academic learning, vocabulary knowledge, than was the total years of education obtained. Results support the hypothesis that methamphetamine use interferes with the quantity and quality of educational exposure, leading to under- and overestimation of cognitive function and academic learning, respectively. Copyright © 2011. Published by Elsevier Ireland Ltd.

  15. Morphometric abnormalities of the lateral ventricles in methamphetamine-dependent subjects☆

    PubMed Central

    Jeong, Hyeonseok S.; Lee, Sunho; Yoon, Sujung; Jung, Jiyoung J.; Cho, Han Byul; Kim, Binna N.; Ma, Jiyoung; Ko, Eun; Im, Jooyeon Jamie; Ban, Soonhyun; Renshaw, Perry F.; Lyoo, In Kyoon

    2017-01-01

    Background The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects. Methods High-resolution brain structural images were obtained from 37 methamphetamine-dependent subjects and 25 demographically matched healthy individuals. Using a combined volumetric and surface-based morphometric approach, the structural variability of the lateral ventricles, with respect to extent and location, was examined. Results Methamphetamine-dependent subjects had an enlarged right lateral ventricle compared with healthy individuals. Morphometric analysis revealed a region-specific pattern of lateral ventricular expansion associated with methamphetamine dependence, which was mainly distributed in the areas adjacent to the ventral striatum, medial prefrontal cortex, and thalamus. Conclusions Patterns of shape decomposition in the lateral ventricles may have relevance to the structural vulnerability of the prefrontal-ventral striatal-thalamic circuit to methamphetamine-induced neurotoxicity. PMID:23769159

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

    PubMed Central

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

    2009-01-01

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

  17. Pharmacotherapeutic agents in the treatment of methamphetamine dependence.

    PubMed

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

    2017-05-01

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

  18. 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.

  19. 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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  2. Predicting adherence to treatment for methamphetamine dependence from neuropsychological and drug use variables.

    PubMed

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

    2009-11-01

    Although some individuals who abuse methamphetamine have considerable cognitive deficits, no prior studies have examined whether neurocognitive functioning is associated with outcome of treatment for methamphetamine dependence. In an outpatient clinical trial of bupropion combined with cognitive behavioral therapy and contingency management (Shoptaw, S., Heinzerling, K.G., Rotheram-Fuller, E., Steward, T., Wang, J., Swanson, A.N., De La Garza, R., Newton, T., Ling, W., 2008. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug Alcohol Depend 96, 222-232.), 60 methamphetamine-dependent adults completed three tests of reaction time and working memory at baseline. Other variables that were collected at baseline included measures of drug use, mood/psychiatric functioning, employment, social context, legal status, and medical status. We evaluated the relative predictive value of all baseline measures for treatment outcome using Classification and Regression Trees (CART; Breiman, L., Friedman, J.H., Olshen, R.A., Stone, C.J., 1984. Classification and Regression Trees. Wadsworth, Belmont, CA.), a nonparametric statistical technique that produces easily interpretable decision rules for classifying subjects that are particularly useful in clinical settings. Outcome measures were whether or not a participant completed the trial and whether or not most urine tests showed abstinence from methamphetamine abuse. Urine-verified methamphetamine abuse at the beginning of the study was the strongest predictor of treatment outcome; two psychosocial measures (e.g., nicotine dependence and Global Assessment of Functioning) also offered some predictive value. A few reaction time and working memory variables were related to treatment outcome, but these cognitive measures did not significantly aid prediction after adjusting for methamphetamine usage at the beginning of the study. On the basis of these findings, we recommend that research

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

    PubMed

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

    2009-03-01

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

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

    PubMed

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

    There is not an approved pharmacotherapy for treating methamphetamine use disorder. This study sought to determine the effects of acute buspirone treatment on the subjective and cardiovascular effects of oral methamphetamine in order to provide an initial assessment of the utility, safety, and tolerability of buspirone for managing methamphetamine use disorder. We predicted that acute buspirone administration would reduce the subjective effects of methamphetamine. We also predicted that the combination of buspirone and methamphetamine would be safe and well tolerated. Ten subjects completed the protocol, which tested three methamphetamine doses (0, 15, and 30mg) in combination with two buspirone doses (0 and 30mg) across 6 experimental sessions. Subjective effects and physiological measures were collected at regular intervals prior to and after dose administration. Methamphetamine produced prototypical subjective and cardiovascular effects. Acute buspirone administration increased some of the abuse-related subjective effects of methamphetamine and also attenuated some cardiovascular effects. The combination of oral methamphetamine and buspirone was safe and well tolerated. Acute buspirone administration may increase the abuse liability of oral methamphetamine. Chronic buspirone dosing studies remain to be conducted, but given preclinical findings and the outcomes of this work, the utility of buspirone for treating methamphetamine use disorder appears limited. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Neural correlates of affect processing and aggression in methamphetamine dependence.

    PubMed

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

    2011-03-01

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

  6. 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 ...

  7. Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment-seeking, methamphetamine-dependent individuals.

    PubMed

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

    2007-03-30

    Previously, we have shown that orally administered topiramate, a sulfamate-substituted fructopyranose derivative, appears to accentuate rather than diminish some aspects of methamphetamine-induced positive subjective mood and cognitive performance. One possible mechanism by which this might occur would be for topiramate to increase plasma methamphetamine level. Such an effect also would be expected to enhance methamphetamine-induced hemodynamic response. We, therefore, studied -- in the same experiment from which the previous findings originated -- the effects of topiramate on the kinetic profile and hemodynamic response to methamphetamine. In a 27-day inpatient study, 10 methamphetamine-dependent individuals participated in a double-blind, placebo-controlled, cross-over design, with oral doses of topiramate (0, 100, and 200 mg) administered as a pretreatment before intravenous doses of methamphetamine (0, 15, and 30 mg). The 3x3 factorial combination of topiramate and methamphetamine resulted in a sequence of the nine treatments administered to each subject in an order determined by a 9x9 Latin Square design. Methamphetamine alone was associated with prototypical increases in hemodynamic response that were not altered in the presence of topiramate. While there was no significant kinetic interaction between topiramate and methamphetamine, there was a non-significant trend for topiramate to increase plasma methamphetamine level. No significant adverse events were reported. The combination of topiramate and methamphetamine at pharmacologically relevant doses appears to be safe. Larger laboratory studies with chronic dosing regimens are needed to establish whether or not there is a kinetic interaction between topiramate and methamphetamine.

  8. KINETIC AND CARDIOVASCULAR EFFECTS OF ACUTE TOPIRAMATE DOSING AMONG NON-TREATMENT-SEEKING, METHAMPHETAMINE-DEPENDENT INDIVIDUALS

    PubMed Central

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

    2007-01-01

    Previously, we have shown that orally administered topiramate, a sulfamate-substituted fructopyranose derivative, appears to accentuate rather than diminish some aspects of methamphetamine-induced positive subjective mood and cognitive performance. One possible mechanism by which this might occur would be for topiramate to increase plasma methamphetamine level. Such an effect also would be expected to enhance methamphetamine-induced hemodynamic response. We, therefore, studied — in the same experiment from which the previous findings originated — the effects of topiramate on the kinetic profile and hemodynamic response to methamphetamine. In a 27-day inpatient study, 10 methamphetamine-dependent individuals participated in a double-blind, placebo-controlled, cross-over design, with oral doses of topiramate (0, 100, and 200 mg) administered as a pretreatment before intravenous doses of methamphetamine (0, 15, and 30 mg). The 3 × 3 factorial combination of topiramate and methamphetamine resulted in a sequence of the nine treatments administered to each subject in an order determined by a 9 × 9 Latin Square design. Methamphetamine alone was associated with prototypical increases in hemodynamic response that were not altered in the presence of topiramate. While there was no significant kinetic interaction between topiramate and methamphetamine, there was a non-significant trend for topiramate to increase plasma methamphetamine level. No significant adverse events were reported. The combination of topiramate and methamphetamine at pharmacologically relevant doses appears to be safe. Larger laboratory studies with chronic dosing regimens are needed to establish whether or not there is a kinetic interaction between topiramate and methamphetamine. PMID:17184890

  9. [Secondary development of psychological dependence in a methamphetamine dependent].

    PubMed

    Edakubo, T; Kaneko, T; Kato, N

    1991-04-01

    A case of methamphetamine dependence was presented, who had used a large amount of the drug for a long time during both of the first and the second period of its prevalence. He led a socially and psychologically stable life with neither drug habits nor episodes of flash-back phenomenon in 20's and 30's of his age. While in the former period of the prevalence, visual illusion had occurred in him 3 months after the first injection of the drug, in the latter, auditory hallucination occurred in a month after the initiation of the reinjection. This hallucination was so invasive and persistent that he became insomniac and could not keep stable daily life. Recently the auditory hallucination has disappeared by the reinjection of the drug, resulting in releasing him from the sufferings like insomnia, and then promoting the drug use more frequently. Even at the law court to decide the penalty against his illegal drug use, he recurrently insisted that methamphetamine was his necessity in order to be freed from the hallucination and keep stable daily life. He declared his intention not to abandon his drug habit in spite of any punishments. On the central nervous system (CNS) depressants such as the morphine- and barbiturate-type drug, the psychological dependence is brought about secondarily by the mechanism to avoid the withdrawal symptoms. On the other hand, the secondary development of psychological dependence through avoidance of the chronic toxicity by the acute drug effect itself, should be considered as one of the characteristics of the CNS stimulants like methamphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-11-01

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

  14. Methamphetamine

    MedlinePlus

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

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

    PubMed

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

    2012-04-27

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

  16. Poor Response to Sertraline in Methamphetamine Dependence is Associated with Sustained Craving for Methamphetamine

    PubMed Central

    Zorick, Todd; Sugar, Catherine A.; Hellemann, Gerhard; Shoptaw, Steve; London, Edythe D.

    2011-01-01

    Background Depression is common among individuals with methamphetamine (MA) use disorders. As agents that enhance serotonergic function are frequently used to treat depression, one might predict that they would be useful medications for MA dependence. However, clinical trials of serotonergic agents for MA addiction have been unsuccessful. Objective To identify factors that distinguish MA-dependent research participants who increased MA self-administration while receiving treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline from other groups of participants. Method Using a dataset from a 12-week randomized, placebo-controlled trial of sertraline (100 mg daily) for MA addiction, we identified participants who had completed at least 8 weeks of the trial (n=61 sertraline, n=68 placebo). We compared the proportions of MA-positive urine tests for weeks 8–12 of the trial for these subjects to their pre-randomization baseline, and identified those subjects who increased MA use during treatment. Using classification trees, we then assessed all data collected during the study to identify factors associated with increasing MA use during treatment with sertraline, compared to placebo. Results More subjects in the sertraline condition increased MA use during treatment (n=13) than in the placebo condition (n=5; p=0.03). Classification trees identified multiple factors from both pre-treatment and in-treatment data that were associated with increased MA use during treatment. Only elevated in-treatment craving for MA specifically characterized subjects in the sertraline group who increased their MA use. Conclusions Some MA-abusing individuals treated with SSRIs have sustained craving with an increased propensity to relapse during treatment despite psychosocial treatment interventions. PMID:21592681

  17. Poor response to sertraline in methamphetamine dependence is associated with sustained craving for methamphetamine.

    PubMed

    Zorick, Todd; Sugar, Catherine A; Hellemann, Gerhard; Shoptaw, Steve; London, Edythe D

    2011-11-01

    Depression is common among individuals with methamphetamine (MA) use disorders. As agents that enhance serotonergic function are frequently used to treat depression, one might predict that they would be useful medications for MA dependence. However, clinical trials of serotonergic agents for MA addiction have been unsuccessful. To identify factors that distinguish MA-dependent research participants who increased MA self-administration while receiving treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline from other groups of participants. Using a dataset from a 12-week randomized, placebo-controlled trial of sertraline (100mg daily) for MA addiction, we identified participants who had completed at least 8 weeks of the trial (n=61 sertraline, n=68 placebo). We compared the proportions of MA-positive urine tests for weeks 8-12 of the trial for these subjects to their pre-randomization baseline, and identified those subjects who increased MA use during treatment. Using classification trees, we then assessed all data collected during the study to identify factors associated with increasing MA use during treatment with sertraline, compared to placebo. More subjects in the sertraline condition increased MA use during treatment (n=13) than in the placebo condition (n=5; p=0.03). Classification trees identified multiple factors from both pre-treatment and in-treatment data that were associated with increased MA use during treatment. Only elevated in-treatment craving for MA specifically characterized subjects in the sertraline group who increased their MA use. Some MA-abusing individuals treated with SSRIs have sustained craving with an increased propensity to relapse during treatment despite psychosocial treatment interventions. Published by Elsevier Ireland Ltd.

  18. 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

  19. Neuropsychological function and delay discounting in methamphetamine-dependent individuals.

    PubMed

    Hoffman, William F; Moore, Meredith; Templin, Raymond; McFarland, Bentson; Hitzemann, Robert J; Mitchell, Suzanne H

    2006-10-01

    Methamphetamine (MA) dependence accounts for substantial neuropsychiatric morbidity. Furthermore, there is evidence in the literature of psychiatric and cognitive impairment in chronic users. This report compares the general psychiatric and cognitive functioning, including impulsive decision-making, of individuals dependent on MA and normal controls. Forty-one currently abstinent individuals in treatment for MA dependence and 41 controls participated. Controls were selected to minimize group differences in age and gender. MA users met DSM-IV criteria for MA dependence, had average daily use of 0.5 g/day (0.5-6 g/day), had been abstinent at least 2 weeks (2-24 weeks), and did not currently meet criteria for other Axis I psychiatric disorders. Psychiatric symptoms were rated on standardized scales. Cognitive function was assessed with a battery of standardized neuropsychological tests. Impulsivity was assessed using a delay discounting task, which measured preference for small, immediate, and large delayed rewards. The MA group reported more psychiatric symptoms than controls, and was impaired relative to controls on the Babcock Story Recall-Delayed and the Rey Auditory Verbal Learning Test. MA-dependent subjects discounted delayed rewards more than controls, and this measure of impulsivity was correlated with memory impairment in the MA group but not in the controls. MA-dependent individuals are more impulsive than controls, and this may be causally related to memory deficits but was unrelated to any other measure of psychiatric or cognitive impairment or any drug use history variable.

  20. Prosthodontics treatment considerations for methamphetamine-dependent patients.

    PubMed

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

    2015-01-01

    Overt dental disease is a distinguishing comorbidity associated with methamphetamine abuse, necessitating the need for special management to maximize treatment benefits. As this highly addictive stimulant increases in popularity, it has become imperative that clinicians are equipped to thoughtfully provide comprehensive care for these patients. This article reviews the impact of methamphetamine to systemic and oral health and proposes a comprehensive treatment plan and sequence for the methamphetamine-dependent patient. A multidisciplinary approach is recommended. Destructive oral and psychological changes must be identified and controlled. A thorough risk assessment, caries control, and preventative plan should be established before initiating prosthodontic treatment. Patient motivation, support, and a timely recall schedule are integral for dental longevity. © 2015 by the American College of Prosthodontists.

  1. Striatal Dopamine D2/D3 Receptor Availability is Reduced in Methamphetamine Dependence and is Linked to Impulsivity

    PubMed Central

    Lee, Buyean; London, Edythe D.; Poldrack, Russell A.; Farahi, Judah; Nacca, Angelo; Monterosso, John R.; Mumford, Jeanette A.; Bokarius, Andrew V.; Dahlbom, Magnus; Mukherjee, Jogeshwar; Bilder, Robert M.; Brody, Arthur L.; Mandelkern, Mark A.

    2010-01-01

    While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D2/D3 receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [18F]fallypride to measure striatal dopamine D2/D3 receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales (p < 0.001). Volume-of-interest analysis found lower striatal D2/D3 receptor availability in methamphetamine-dependent than in healthy control subjects (p < 0.01) and a negative relationship between impulsiveness and striatal D2/D3 receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D2/D3 receptor availability in left caudate nucleus and right lateral putamen/claustrum (p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects, and the lateral putamen/claustrum of control subjects were observed at a weaker threshold (p < 0.12 corrected). The findings suggest that low striatal D2/D3 receptor availability may mediate impulsive temperament and thereby influence addiction. PMID:19940168

  2. Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity.

    PubMed

    Lee, Buyean; London, Edythe D; Poldrack, Russell A; Farahi, Judah; Nacca, Angelo; Monterosso, John R; Mumford, Jeanette A; Bokarius, Andrew V; Dahlbom, Magnus; Mukherjee, Jogeshwar; Bilder, Robert M; Brody, Arthur L; Mandelkern, Mark A

    2009-11-25

    While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D(2)/D(3) receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [(18)F]fallypride to measure striatal dopamine D(2)/D(3) receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales (p < 0.001). Volume-of-interest analysis found lower striatal D(2)/D(3) receptor availability in methamphetamine-dependent than in healthy control subjects (p < 0.01) and a negative relationship between impulsiveness and striatal D(2)/D(3) receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D(2)/D(3) receptor availability in left caudate nucleus and right lateral putamen/claustrum (p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold (p < 0.12 corrected). The findings suggest that low striatal D(2)/D(3) receptor availability may mediate impulsive temperament and thereby influence addiction.

  3. 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 ...

  4. Pharmacological approaches to methamphetamine dependence: a focused review

    PubMed Central

    Karila, Laurent; Weinstein, Aviv; Aubin, Henri-Jean; Benyamina, Amine; Reynaud, Michel; Batki, Steven L

    2010-01-01

    Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research. PMID:20565449

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

    PubMed

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

    2011-09-01

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

  6. Extinction of Drug Cue Reactivity in Methamphetamine-Dependent Individuals

    PubMed Central

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

    2010-01-01

    Conditioned responses to drug-related environmental cues (such as craving) play a critical role in relapse to drug use. Animal models demonstrate that repeated exposure to drug-associated cues in the absence of drug administration leads to the extinction of conditioned responses, but the few existing clinical trials focused on extinction of conditioned responses to drug-related cues in drug-dependent individuals show equivocal results. The current study examined drug-related cue reactivity and response extinction in a laboratory setting in methamphetamine-dependent individuals. Methamphetamine cue-elicited craving was extinguished during two sessions of repeated (3) within-session exposures to multi-modal (picture, video, and in-vivo) cues, with no evidence of spontaneous recovery between sessions. A trend was noted for a greater attenuation of response in participants with longer (4-7 day) inter-session intervals. These results indicate that extinction of drug-cue conditioned responding occurs in methamphetamine-dependent individuals, offering promise for the development of extinction- based treatment strategies. PMID:20538262

  7. Altered reward expectancy in individuals with recent methamphetamine dependence.

    PubMed

    Bischoff-Grethe, Amanda; Connolly, Colm G; Jordan, Stephan J; Brown, Gregory G; Paulus, Martin P; Tapert, Susan F; Heaton, Robert K; Woods, Steven P; Grant, Igor

    2017-01-01

    Chronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence. Participants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes. METH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes. METH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.

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

    PubMed

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

    2010-09-01

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

  9. 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

  10. Discriminative-stimulus, subject-rated, and physiological effects of methamphetamine in humans pretreated with aripiprazole.

    PubMed

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

    2011-08-01

    Methamphetamine is thought to produce its behavioral effects by facilitating release of dopamine, serotonin (5-HT) and norepinephrine. Results from animal studies support this notion, whereas results from human laboratory studies have not consistently demonstrated the importance of monoamine systems in the behavioral effects of methamphetamine. Human drug-discrimination procedures are well suited to assess neuropharmacological mechanisms of the training drug by studying pharmacological manipulation. In this human laboratory study, 6 participants with a history of recreational stimulant use learned to discriminate 10 mg oral methamphetamine. After acquiring the discrimination (ie, ≥ 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 (eg, 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.

  11. Typologies of positive psychotic symptoms in methamphetamine dependence

    PubMed Central

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

    2014-01-01

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

  12. Typologies of positive psychotic symptoms in methamphetamine dependence.

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2014-06-01

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

  14. Exercise training improves heart rate variability after methamphetamine dependency.

    PubMed

    Dolezal, Brett Andrew; Chudzynski, Joy; Dickerson, Daniel; Mooney, Larissa; Rawson, Richard A; Garfinkel, Alan; Cooper, Christopher B

    2014-06-01

    Heart rate variability (HRV) reflects a healthy autonomic nervous system and is increased with physical training. Methamphetamine dependence (MD) causes autonomic dysfunction and diminished HRV. We compared recently abstinent methamphetamine-dependent participants with age-matched, drug-free controls (DF) and also investigated whether HRV can be improved with exercise training in the methamphetamine-dependent participants. In 50 participants (MD = 28; DF = 22), resting heart rate (HR; R-R intervals) was recorded over 5 min while seated using a monitor affixed to a chest strap. Previously reported time domain (SDNN, RMSSD, pNN50) and frequency domain (LFnu, HFnu, LF/HF) parameters of HRV were calculated with customized software. MD were randomized to thrice-weekly exercise training (ME = 14) or equal attention without training (MC = 14) over 8 wk. Groups were compared using paired and unpaired t-tests. Statistical significance was set at P ≤ 0.05. Participant characteristics were matched between groups (mean ± SD): age = 33 ± 6 yr; body mass = 82.7 ± 12 kg, body mass index = 26.8 ± 4.1 kg·min. Compared with DF, the MD group had significantly higher resting HR (P < 0.05), LFnu, and LF/HF (P < 0.001) as well as lower SDNN, RMSSD, pNN50, and HFnu (all P < 0.001). At randomization, HRV indices were similar between ME and MC groups. However, after training, the ME group significantly (all P < 0.001) increased SDNN (+14.7 ± 2.0 ms, +34%), RMSSD (+19.6 ± 4.2 ms, +63%), pNN50 (+22.6% ± 2.7%, +173%), HFnu (+14.2 ± 1.9, +60%), and decreased HR (-5.2 ± 1.1 bpm, -7%), LFnu (-9.6 ± 1.5, -16%), and LF/HF (-0.7 ± 0.3, -19%). These measures did not change from baseline in the MC group. HRV, based on several conventional indices, was diminished in recently abstinent, methamphetamine-dependent individuals. Moreover, physical training yielded a marked increase in HRV, representing increased vagal modulation or improved autonomic balance.

  15. Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence.

    PubMed

    Longo, Marie; Wickes, Wendy; Smout, Matthew; Harrison, Sonia; Cahill, Sharon; White, Jason M

    2010-01-01

    To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dexamphetamine in people dependent on methamphetamine. Randomized, double-blind, placebo-controlled trial. Forty-nine methamphetamine-dependent drug users from Drug and Alcohol Services South Australia (DASSA) clinics. Participants were assigned randomly to receive up to 110 mg/day sustained-release dexamphetamine (n = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of the study medication over an additional 4 weeks. Medication was taken daily under pharmacist supervision. Primary outcome measures included treatment retention, measures of methamphetamine consumption (self-report and hair analysis), degree of methamphetamine dependence and severity of methamphetamine withdrawal. Hair samples were analysed for methamphetamine using liquid chromatography-mass spectrometry. Treatment retention was significantly different between groups, with those who received dexamphetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo (P = 0.014). There were significant reductions in self-reported methamphetamine use between baseline and follow-up within each group (P < 0.0001), with a trend to a greater reduction among the dexamphetamine group (P = 0.086). Based on hair analysis, there was a significant decrease in methamphetamine concentration for both groups (P < 0.0001). At follow-up, degree of methamphetamine dependence was significantly lower in the dexamphetamine group (P = 0.042). Dexamphetamine maintenance was not associated with serious adverse events. The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dexamphetamine group, together with the general decreases in methamphetamine use, degree of dependence

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-06-01

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

  18. Gray matter abnormalities in cocaine versus methamphetamine-dependent patients: a neuroimaging meta-analysis.

    PubMed

    Hall, Matthew G; Alhassoon, Omar M; Stern, Mark J; Wollman, Scott C; Kimmel, Christine L; Perez-Figueroa, Adlyn; Radua, Joaquim

    2015-01-01

    Voxel-based morphometry has been used to explore gray matter alterations in cocaine and methamphetamine dependence. However, the results of this research are inconsistent. The current study meta-analytically examined neuroimaging findings of all studies published before 2014 using the Anisotropic Effect-Size Signed Differential Mapping (ES-SDM). Independent investigators searched four major databases for relevant neuroimaging studies involving cocaine and methamphetamine dependence. Nine cocaine and four methamphetamine studies met inclusion criteria. Results indicated that cocaine- and methamphetamine-dependent patients share overlapping regional gray matter abnormalities compared to healthy controls. However, subgroup analysis showed some regional differences; with methamphetamine showing more prominent reductions in the left superior temporal gyrus and the right inferior parietal lobe. Reductions in the right insula and the left superior frontal gyrus were more prominent in cocaine dependence. Moderator analyses indicated that with longer use, cocaine is associated with reductions in the right hippocampus, right middle temporal gyrus, and right inferior frontal gyrus, while methamphetamine is associated with reductions in the left precentral gyrus and the right supramarginal gyrus. These findings indicate that cocaine and methamphetamine dependence are significantly and differentially associated with gray matter abnormalities. Results also point to possible gray matter recovery after abstinence from methamphetamine. Although the sample size was adequate, these findings should be considered preliminary and analyses should be revisited with additional primary research focusing on long or short-term duration of use, as well as the length of abstinence.

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

    PubMed

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

    2007-10-01

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

  20. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. 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

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

    PubMed Central

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

    2016-01-01

    Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric acid type A (GABAA) receptors (e.g., 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 6–7 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

  5. 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.

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

    PubMed

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

    2010-01-15

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

  7. 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.

  8. Exercise for Methamphetamine Dependence: Rationale, Design, and Methodology

    PubMed Central

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

    2015-01-01

    Background Effective pharmacotherapies to treat methamphetamine (MA) dependence have not been identified, and behavioral therapies are marginally effective. Based on behavioral studies demonstrating the potential efficacy of aerobic exercise for improving depressive symptoms, anxiety, cognitive deficits, and substance use outcomes, the study described here is examining exercise as a potential treatment for MA-dependent individuals. Methods This study is randomizing 150 participants with MA dependence at a residential treatment facility for addictive disorders to receive either a thrice-weekly structured aerobic and resistance exercise intervention or a health education condition. Recruitment commenced in March, 2010. Enrollment and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions Seeking evidence for a possibly effective adjunct to traditional behavioral approaches for treatment of MA dependence, this study is assessing the ability of an 8-week aerobic and resistance exercise protocol to reduce relapse to MA use during a 12-week follow-up period after discharge from residential-based treatment. The study also is evaluating improvements in health and functional outcomes during and after the protocol. This paper describes the design and methods of the study. PMID:24291456

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

    PubMed

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

    2016-04-30

    This study examined correlates of transient versus persistent psychotic symptoms among people dependent on methamphetamine. A longitudinal prospective cohort study of dependent methamphetamine users who did not meet DSM-IV criteria for lifetime schizophrenia or mania. Four non-contiguous one-month observation periods were used to identify participants who had a) no psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient psychotic symptoms, n=85); and, (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent psychotic symptoms, n=37). Psychotic symptoms were defined as a score of 4 or greater on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content. Relative no psychotic symptoms, both transient and persistent psychotic symptoms were associated with childhood conduct disorder and comorbid anxiety disorders. Earlier onset methamphetamine use and being male were more specifically related to transient psychotic symptoms, while a family history of a primary psychotic disorder and comorbid major depression were specifically related to persistent psychotic symptoms. We conclude that there are overlapping but also distinct clinical correlates of transient versus persistent psychotic symptoms, suggesting potentially heterogeneous etiological pathways underpinning the psychotic phenomena seen amongst people who use methamphetamine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2006-08-01

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

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

    PubMed

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

    2007-01-30

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

  12. Exercise Training Improves Heart Rate Variability after Methamphetamine Dependency

    PubMed Central

    Dolezal, Brett A.; Chudzynski, Joy; Dickerson, Daniel; Mooney, Larissa; Rawson, Richard A.; Garfinkel, Alan; Cooper, Christopher B.

    2014-01-01

    Purpose Heart rate variability (HRV) reflects a healthy autonomic nervous system and is increased with physical training. Methamphetamine dependence (MD) causes autonomic dysfunction and diminished HRV. We compared recently abstinent MD participants with age-matched, drug free controls (DF) and also investigated whether HRV can be improved with exercise training in the MD participants. Methods In 50 participants (MD=28; DF=22) resting heart rate (R-R intervals) was recorded over 5 min while seated using a monitor affixed to a chest strap. Previously reported time-domain (SDNN, RMSSD, pNN50) and frequency-domain (LFnu, HFnu, LF/HF) parameters of HRV were calculated with customized software. MD were randomized to thrice weekly exercise training (ME=14) or equal attention without training (MC=14) over 8 weeks. Groups were compared using paired and unpaired t-tests. Statistical significance was set at P≤0.05. Results Participant characteristics were matched between groups: age 33±6 years; body mass 82.7±12 kg, BMI 26.8±4.1 kg•min−2, mean±SD. Compared with DF, the MD group had significantly higher resting heart rate (P<0.05), LFnu, and LF/HF (P<0.001) as well as lower SDNN, RMSSD, pNN50 and HFnu (all P<0.001). At randomization, HRV indices were similar between ME and MC groups. However, after training, the ME group significantly (all P<0.001) increased SDNN (+14.7±2.0 ms, +34%), RMSSD (+19.6±4.2 ms, +63%), pNN50 (+22.6±2.7%, +173%), HFnu (+14.2±1.9, +60%) and decreased HR (−5.2±1.1 beats·min−1, −7%), LFnu (−9.6±1.5, −16%) and LF/HF (−0.7±0.3, −19%). These measures did not change from baseline in the MC group. Conclusion HRV, based on several conventional indices, was diminished in recently abstinent, methamphetamine dependent individuals. Moreover, physical training yielded a marked increase of HRV representing increased vagal modulation or improved autonomic balance. PMID:24162556

  13. Drug abstinence and cognitive control in methamphetamine-dependent individuals.

    PubMed

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

    2009-10-01

    Chronic methamphetamine (MA) abuse is associated with disruption of frontostriatal function as well as deficits in cognitive control. To examine the relationship between drug use patterns and cognitive deficits, we pooled previously published behavioral data with new data collected using the Stroop Attention Test. Subject groups are composed of 38 MA-abusing individuals who recently initiated abstinence (36.1 +/- 8.8 years of age), 27 MA-abusing individuals who had initiated abstinence more than 1 year prior to study (38.7 +/- 7.7 years of age), and 33 non-substance-abusing controls (33.9 +/- 8.5 years of age). The recently abstinent MA-abusing individuals exhibited greater Stroop reaction time (RT) interference compared with both the control group (p = .001) and the long-term abstinent MA-abusing individuals (p = .01). No difference was seen between long-term abstinent MA-abusing individuals and controls (p = .87). Stroop RT interference correlated positively with both duration of drug use (p = .003) and drug abstinence (p = .05). The data in the current study provide evidence that cognitive function may improve with protracted drug abstinence.

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

    PubMed

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

    2011-04-01

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

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

    PubMed

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

    2016-02-01

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

  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.

  17. Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment.

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2010-10-01

    It has been well documented that cocaine and methamphetamine use can lead to the onset of psychotic symptoms similar to schizophrenia. However, the research and literature on gender differences and stimulant-induced psychosis have been mixed. The primary aim of this study was to investigate gender differences in the reporting of psychotic symptoms in cocaine- versus methamphetamine-dependent individuals. Participants were recruited from the Los Angeles, California, community via radio and newspaper advertisements. All met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for cocaine or methamphetamine dependence, and all reported either methamphetamine or cocaine as their primary drug of abuse. During a screening interview, participants answered questions from the Psychotic Symptom Assessment Scale, which characterizes various types of psychotic symptoms during drug use ("while high") or during periods of nonuse ("while abstinent"). Participants included 42 cocaine-dependent individuals (27 men, 15 women) and 43 methamphetamine-dependent individuals (25 men, 18 women). Among cocaine users, there were no significant differences between men and women with regard to ethnicity, years of use, route of administration, and amount used in the past week, though they differed significantly with regard to age (P = 0.029). In the "while abstinent" condition, women were significantly more likely than men to report experiencing auditory hallucinations (13% vs 0%, respectively; P = 0.050) and tactile hallucinations (20% vs 0%; P = 0.016), whereas men were more likely to report delusions of grandeur (48% vs 6%; P = 0.006). During the "while high" condition, women were significantly more likely than men to report delusions of grandeur (13% vs 0%, respectively; P = 0.050), tactile hallucinations (33% vs 0%; P = 0.001), and olfactory hallucinations (13% vs 0%; P = 0.050). Among methamphetamine users, there were no significant differences between men and

  19. Methamphetamine activates reward circuitry in drug naïve human subjects.

    PubMed

    Völlm, Birgit A; de Araujo, Ivan E; Cowen, Philip J; Rolls, Edmund T; Kringelbach, Morten L; Smith, Katharine A; Jezzard, Peter; Heal, Ronald J; Matthews, Paul M

    2004-09-01

    Amphetamines are highly addictive drugs that have pronounced effects on emotional and cognitive behavior in humans. These effects are mediated through their potent dopaminergic agonistic properties. Dopamine has also been implicated in the modulation of responses of the 'reward circuit' in animal and human studies. In this study we use functional magnetic resonance imaging (fMRI) to identify the brain circuitry involved in the psychostimulant effect of methamphetamine in psychostimulant-naïve human subjects. Seven healthy volunteers were scanned in a 3T MR imaging system. They received single-blind intravenous infusions of methamphetamine (0.15 mg/kg), and rated their experience of 'mind-racing' on a button press throughout the experiment. Data were analyzed with statistical parametric mapping methods. Amphetamine administration activated the medial orbitofrontal cortex, the rostral part of the anterior cingulate cortex, and the ventral striatum. Ratings of 'mind-racing' after methamphetamine infusion correlated with activations in the rostral part of the anterior cingulate cortex and in the ventral striatum. In addition, activations in the medial orbitofrontal cortex were independent of motor and related responses involved in making the ratings. These findings indicate that the first administration of a psychostimulant to human subjects activates classical reward circuitry. Our data also support recent hypotheses suggesting a central role for the orbitofrontal cortex in drug reinforcement and the development of addiction.

  20. Dopamine D3 receptors as a therapeutic target for methamphetamine dependence.

    PubMed

    Paterson, Neil E; Vocci, Frank; Sevak, Rajkumar J; Wagreich, Eric; London, Edythe D

    2014-01-01

    Methamphetamine (MA) use disorders are major public health problems nationally and worldwide and treatment remains an unmet need. (1) To review preclinical and clinical studies identifying the dopamine D3 receptor as a therapeutic target for substance use disorders (SUDs), including MA dependence, (2) to consider buspirone (Buspar®) as a potential medication based on its dopamine D3 receptor antagonist properties, and (3) to evaluate the safety and initial efficacy of buspirone in a pilot study of MA-dependent individuals. Literature on the dopamine D3 receptor as a therapeutic target and on the potential of buspirone as a novel therapy for MA dependence was reviewed. The cardiovascular and subjective effects of intravenous MA challenge were assessed in five non-treatment seeking individuals. Participants met DSM-IV criteria for MA dependence and were treated subacutely (9 days) with buspirone (60 mg daily). The literature identified the dopamine D3 receptor as a therapeutic target for MA dependence, a safe and approved medication, and a valuable opportunity to re-purpose buspirone for treating MA dependence and perhaps other SUDs. Pilot data (n = 5) indicated that buspirone is safe in MA-using individuals and comparison against historical placebo data from this laboratory suggested that at least some aspects of the subjective properties of MA may be diminished during buspirone treatment. Future studies should include a small-scale, placebo-controlled Phase IIa trial of buspirone in MA dependence.

  1. A systematic review of cognitive and/or behavioural therapies for methamphetamine dependence

    PubMed Central

    Lee, Nicole K; Rawson, Richard A.

    2015-01-01

    Introduction and aims The use of methamphetamine is widespread and poses significant challenges for treatment providers. Much of the treatment knowledge about this group has been extrapolated from studies of treatment for cocaine dependence. Medications have been shown to be of limited effectiveness for methamphetamine users, making psychological interventions the treatment of choice. Design and methods This paper describes a systematic review of cognitive-behavioural and behavioural interventions for methamphetamine users. A systematic search of published literature was undertaken focusing only on randomised trials. Results There were a relatively small number of intervention studies that compared cognitive-behavioural or behavioural interventions using randomised trial methodology. Most commonly, studies examined cognitive behaviour therapy (CBT) and/or contingency management (CM). Treatment with CBT appears to be associated with reductions in methamphetamine use and other positive changes ,even over very short periods of treatment (2 and 4 sessions). CM studies found a significant reduction of methamphetamine during application of the procedure, but it is not clear if these gains are sustained at post-treatment follow-up. Discussion and conclusion Further research into cognitive behavioural and behavioural treatments for methamphetamine users is required, with a focus on improving longevity of the effect of intervention. PMID:18368613

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

    PubMed

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

    2011-09-01

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

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

    PubMed Central

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

    2011-01-01

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

  4. Methamphetamine dependent individuals show attenuated brain response to pleasant interoceptive stimuli.

    PubMed

    May, April C; Stewart, Jennifer L; Migliorini, Robyn; Tapert, Susan F; Paulus, Martin P

    2013-08-01

    Mechano-receptive C-fiber (MR-CF) stimulation via slow stroking of C-fiber rich skin areas can be used to probe the relationship between reward and interoception. Individuals with substance use disorders show impaired reward processing, and dysfunctional interoceptive processing of MR-CF may contribute to this dysfunction. This study predicted that methamphetamine dependent (MD) individuals would exhibit altered responses to MR-CF stimulation in brain regions important for interoception. Recently abstinent MD (n=25) and comparison (CTL, n=17) subjects received a pleasant interoceptive stimulus ("Soft Touch" consisting of a slow brush stroke) to the palm or forearm during functional magnetic resonance imaging. Subjects were provided with cues signaling stimulation to examine anticipatory and stimulus-related processing. Subjective responses were measured using visual analog scales (VAS). Groups were similar on behavioral performance and ratings of the interoceptive stimuli, yet MD exhibited lower anterior insula, dorsal striatum, and thalamus activation than CTL, across anticipation and soft touch conditions. The lower the anterior insula activation, the faster the reaction time across conditions in MD, whereas the opposite pattern was evident in CTL. Striatal activation in MD was greater than CTL during anticipation, but lower during soft touch. Greater striatal attenuation was associated with higher VAS pleasantness ratings of soft touch. MD expend fewer brain processing resources during soft touch, a form of positively-valenced interoceptive stimuli, in brain areas that are important for both interoception and reward. Future studies will ascertain if sustained abstinence from methamphetamine use can normalize aberrant neural interoceptive processing. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  6. 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. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. 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…

  8. 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…

  9. Elevated aspartate and alanine aminotransferase levels and natural death among patients with methamphetamine dependence.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-05-14

    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. 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 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. 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.

  12. "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.

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

    PubMed

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

    2017-02-21

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

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

    PubMed Central

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

    2016-01-01

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

  15. Effect of methamphetamine dependence on inhibitory deficits in a novel human open-field paradigm.

    PubMed

    Henry, Brook L; Minassian, Arpi; van Rhenen, Mandy; Young, Jared W; Geyer, Mark A; Perry, William

    2011-06-01

    Methamphetamine (MA) is an addictive psychostimulant associated with neurocognitive impairment, including inhibitory deficits characterized by a reduced ability to control responses to stimuli. While various domains of inhibition such as exaggerated novelty seeking and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar models have not been utilized in human substance abusers. We recently developed a cross-species translational human open-field paradigm, the human behavior pattern monitor (hBPM), consisting of an unfamiliar room containing novel and engaging objects. Previous work demonstrated that manic bipolar subjects exhibit a disinhibited pattern of behavior in the hBPM characterized by increased object interactions. In the current study, we examined the effect of MA dependence on inhibitory deficits using this paradigm. hBPM activity and object interactions were quantified in 16 abstinent MA-dependent individuals and 18 matched drug-free comparison subjects. The Wisconsin card sorting task (WCST) and the positive and negative syndrome scale (PANSS) were administered to assess executive function and psychopathology. MA-dependent participants exhibited a significant increase in total object interactions, time spent with objects, and perseverative object interactions relative to comparison subjects. Greater object interaction was associated with impaired performance on the WCST, higher PANSS scores, and more frequent MA use in the past year. Abstinent MA-dependent individuals exhibited impaired inhibition in the hBPM, displaying increased interaction with novel stimuli. Utilization of this measure may enable assessment of inhibitory deficits relevant to drug-seeking behavior and facilitate development of intervention methods to reduce high-risk conduct in this population.

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

    PubMed

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

    2012-01-01

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

  17. Structural abnormalities in the brains of human subjects who use methamphetamine.

    PubMed

    Thompson, Paul M; Hayashi, Kiralee M; Simon, Sara L; Geaga, Jennifer A; Hong, Michael S; Sui, Yihong; Lee, Jessica Y; Toga, Arthur W; Ling, Walter; London, Edythe D

    2004-06-30

    We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

  18. Low dose, short-term rivastigmine administration does not affect neurocognition in methamphetamine dependent individuals.

    PubMed

    Kalechstein, Ari D; Yoon, Jin H; Croft, Daniel E; Jaeggi, Susanne; Mahoney, James J; De La Garza, Richard

    2011-09-01

    Neurocognitive impairment is a well-documented consequence of methamphetamine addiction. Not surprising, methamphetamine-associated neurocognitive impairment has been identified as an important target of treatment. Thus, this study sought to determine whether rivastigmine, an acetylcholinesterase inhibitor and cognition enhancing agent, could improve neurocognitive performance in a sample of long-term, high-dose methamphetamine addicts who were not seeking treatment at the time of enrollment in the study. This double-blind, placebo-controlled study evaluated whether a daily dose 0, 3, or 6 mg of rivastigmine, administered over six consecutive days, would enhance performance on measures of attention/information processing speed, episodic memory, and executive/frontal lobe functioning relative to test performance at baseline. The results revealed that rivastigmine did not alter neurocognition in this cohort. There are a number of factors that may have mitigated the effects of rivastigmine in this particular study, including especially the short-term, low-dose treatment regimen utilized. The negative findings notwithstanding, the study serves as a springboard for future investigations that will examine whether other medications can alter neurocognition in methamphetamine dependent study participants. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  1. Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence.

    PubMed

    Ezard, Nadine; Dunlop, Adrian; Clifford, Brendan; Bruno, Raimondo; Carr, Andrew; Bissaker, Alexandra; Lintzeris, Nicholas

    2016-12-01

    The treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder. This is a phase 2 dose escalation study of lisdexamfetamine for the treatment of methamphetamine dependence. Twenty individuals seeking treatment for methamphetamine dependence will be recruited at two Australian drug and alcohol services. All participants will undergo a single-blinded ascending-descending dose regime of 100 to 250 mg lisdexamfetamine, dispensed daily on site, over an 8-week period. Participants will be offered counselling as standard care. For the primary objectives the outcome variables will be adverse events monitoring, drug tolerability and regimen completion. Secondary outcomes will be changes in methamphetamine use, craving, withdrawal, severity of dependence, risk behaviour and other substance use. Medication acceptability, potential for non-prescription use, adherence and changes in neurocognition will also be measured. Determining the safety of lisdexamfetamine will enable further research to develop pharmacotherapies for the treatment of methamphetamine dependence. Australian and New Zealand Clinical Trials Registry ACTRN12615000391572 Registered 28(th) April 2015.

  2. Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal.

    PubMed

    Su, Hang; Zhang, Jie; Ren, Wenwei; Xie, Ying; Tao, Jingyan; Zhang, Xiangyang; He, Jincai

    2017-04-01

    Anxiety is often a core element of withdrawal symptoms; however, risk factors associated with anxiety symptoms during the early stage of withdrawal in methamphetamine (METH) users are not well understood. Two hundred ten METH-dependent subjects who had been abstinent for 1 to 7 days were recruited. We used a set of self-administrative questionnaires eliciting information on sociodemographics, detailed drug use history and anxiety. Beck Anxiety Inventory (BAI) was used to measure anxiety symptoms. METH users had a mean BAI score of 6.9; 72 (34.3%) of the study sample had anxiety symptoms during acute METH withdrawal, including 42 (20.0%) with mild anxiety, 25 (11.9%) with moderate anxiety, and 5 (2.4%) with severe anxiety. In addition, gender (female), higher frequency of drug use, and history of polysubstance use were significantly correlated with anxiety symptoms during acute METH withdrawal. Anxiety symptoms appear to be common during the first week of METH abstinence, and several risk factors are identified.

  3. Impulsivity is associated with treatment non-completion in cocaine- and methamphetamine-dependent patients but differs in nature as a function of stimulant-dependence diagnosis

    PubMed Central

    Winhusen, Theresa; Lewis, Daniel; Adinoff, Bryon; Brigham, Gregory; Kropp, Frankie; Donovan, Dennis M.; Seamans, Cindy L.; Hodgkins, Candace C.; DiCenzo, Jessica C.; Botero, Christopher L.; Jones, Davina R.; Somoza, Eugene

    2012-01-01

    Greater impulsivity, assessed by the Barratt Impulsiveness Scale-11 (BIS-11) and Stroop interference scores, has been associated with treatment completion in cocaine-dependent patients. This study evaluated the relationships among impulsivity, stimulant-dependence diagnosis, and treatment completion. Six sites evaluating 12-step facilitation for stimulant abusers obtained the BIS-11 and Stroop from 182 methamphetamine- and/or cocaine-dependent participants. Methamphetamine-dependent, relative to cocaine-dependent, participants evidenced significantly greater BIS-11 Non-planning and Total scores. There was a trend for poorer response inhibition, measured by the Stroop, in cocaine-dependent, relative to methamphetamine-dependent, participants. Accounting for other factors related to treatment completion, BIS-11 Motor score, assessing the tendency to act without thinking, predicted treatment completion for both cocaine-dependent and methamphetamine-dependent patients. These results suggest that methamphetamine-dependent and cocaine-dependent patients may have different impulsivity profiles but that the BIS-11 may be useful in identifying both methamphetamine-dependent and cocaine-dependent patients who are at risk for treatment non-completion. PMID:23305820

  4. 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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2012-01-01

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

  7. P300 event-related potential in abstinent methamphetamine-dependent patients.

    PubMed

    Haifeng, Jiang; Wenxu, Zhuang; Hong, Cheng; Chuanwei, Li; Jiang, Du; Haiming, Sun; Zhikang, Chen; Din, Xu; Jijun, Wang; Min, Zhao

    2015-10-01

    Substance use and abuse are characterized by biases in the attentional processing of substance-related stimuli. There are no event related potential (ERP)-based studies of attentional bias for substance-related cues among methamphetamine (MA) dependent patients. The study aimed to measure changes in P300 event-related potentials elicited by MA-related words in MA-dependent individuals at baseline and after 3 and 6 months of abstinence, examining the relationship of ERP changes to craving. 26 MA-dependent patients (14 male) newly enrolled in two compulsory treatment centers in China and 29 healthy controls (15 male) were included in this study. At baseline (2-3 weeks in treatment) and after 3 and 6 months of abstinence from MA use, we obtained ERP data during a Stroop color-matching task using MA-related and neutral words. Self-reported craving was measured by a Visual Analog Scale (VAS). Increased P300 amplitudes elicited by MA-related words were observed over left-anterior electrode sites. Abnormal P300 amplitudes declined to the normal levels of healthy controls at the end of 3 months of abstinence, and the decrease was maintained up to the end of 6 months of abstinence. The behavioral data did not show similar changes. The positive relationship between the changes of VAS scores for MA craving and the changes of P300 amplitudes over left anterior electrode sites elicited by MA-related words within the first 3 months was significant. These findings highlight the potential use of ERP as an objective index to track changes in subjective MA craving among abstinent MA-dependent patients. Copyright © 2015. Published by Elsevier Inc.

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

    PubMed Central

    Saify, Khyber; Saadat, Mostafa

    2015-01-01

    AIM: Prodynorphin (PDYN; OMIM: 131340) is the precursor of the dynorphin related peptides which plays an important role in drug abuse. Previous studies have been shown that the expression of PDYN is regulated by a genetic polymorphism of VNTR in the promoter region of the gene. MATERIALS AND METHODS: The present case-control study was performed on 52 (41 males, 11 females) methamphetamine dependence patients and 635 (525 males, 110 females) healthy blood donors frequency matched with the patients according to age and gender, as a control group was participated in the study. RESULTS: The genotypes of VNTR PDYN polymorphism were determined using PCR method. The HL (OR = 1.22, 95%CI: 0.67-2.20, P = 0.500) and LL (OR = 0.86, 95%CI: 0.28-2.57, P = 0.792) genotypes does not alter the risk of methamphetamine dependence, in comparison with the HH genotypes. CONCLUSION: The present study revealed no association between the VNTR polymorphism in the promoter region of the PDYN gene and methamphetamine dependence risk. PMID:27275252

  9. Influence of Betaxolol on the Methamphetamine Dependence in Mice.

    PubMed

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

    2016-05-01

    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. 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. 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. These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP.

  10. Influence of Betaxolol on the Methamphetamine Dependence in Mice

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Shoptaw, Steven; Klausner, Jeffrey D; Reback, Cathy J; Tierney, Stephen; Stansell, John; Hare, C Bradley; Gibson, Steven; Siever, Michael; King, William D; Kao, Uyen; Dang, Jeffrey

    2006-08-18

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

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

    PubMed

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

    2011-10-01

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

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

    PubMed

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

    2014-01-30

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

  14. A cognitive behavioral therapy-based text messaging intervention for methamphetamine dependence.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. (1)H-magnetic resonance spectroscopy ((1)H-MRS) in methamphetamine dependence and methamphetamine induced psychosis.

    PubMed

    Howells, Fleur M; Uhlmann, Anne; Temmingh, Henk; Sinclair, Heidi; Meintjes, Ernesta; Wilson, Don; Stein, Dan J

    2014-03-01

    Methamphetamine (MA) use has been shown to decrease n-acetyl-aspartate (NAA), a marker of neuronal integrity and viability, on (1)H magnetic resonance spectroscopy ((1)H-MRS). However, little work has compared (1)H-MRS in MA dependent individuals and MA dependent individuals with MA induced psychotic disorder (MAP). Twenty six participants with MA dependence (sixteen without psychosis, ten with psychosis - MAP) and nineteen healthy controls underwent 2D-chemical shift imaging (1)H-MRS, which included voxels in the anterior cingulate cortices (ACC), dorsolateral prefrontal cortices (DLPFC), and frontal white matter. We compared metabolite concentrations relative to phosphocreatine+creatine (PCr+Cr) for n-acetyl-aspartate (NAA), n-acetyl-aspartate+n-acetyl-aspartyl-glutamate (NAA+NAAG), glutamate (Glu), glutamate+glutamine (Glu+Gln), myo-inositol, and glycerophosphocholine+phosphocholine (GPC+PCh) across groups. The MA groups showed significantly decreased relative NAA metabolite concentrations for right ACC and right DLPFC, compared with control group. The MA dependent group only showed significantly decreased choline metabolites for right DLPFC, compared with control group. The MAP group's relative NAA metabolite concentrations were significantly correlated with age of initial use and duration of MA use, these correlates were not apparent in MA dependent group. MA use is associated with decreased neuronal integrity and viability, specifically in the right ACC and right DLPFC. MA dependence showed active neurodegeneration in the right DLPFC, this was not apparent in the MAP group and may be related to the use of antipsychotic medication in the MAP group. The effects of MA use in MAP suggest that age of initial use presents a mismatch of neuronal plasticity, in frontal white vs. gray matter and duration of use relates to decreased neuronal integrity and viability. Further study is warranted from this initial study of (1)H-MRS in MAP, in particular longitudinal

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

    PubMed

    White, André O; Rauhut, Anthony S

    2014-04-15

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

  18. Time-Dependent Effects of Prazosin on the Development of Methamphetamine Conditioned Hyperactivity and Context-Specific Sensitization in Mice

    PubMed Central

    White, André O.; Rauhut, Anthony S.

    2014-01-01

    The present experiments examined the effects of prazosin, a selective α1-adrenergic receptor antagonist, on the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Mice received an injection of vehicle (distilled water) or prazosin (0.5, 1.0 or 2.0 mg/kg) 30 minutes prior to a second injection of vehicle (saline) or methamphetamine (1.0 mg/kg) during the conditioning sessions (Experiment 1). Following the conditioning sessions, mice were tested for conditioned hyperactivity and then tested for context-specific sensitization. In subsequent experiments, mice received an injection of vehicle (distilled water) or prazosin (2.0 mg/kg) immediately (Experiment 2) or 24 hours (Experiment 3) after the conditioning sessions and then tested for conditioned hyperactivity and context-specific sensitization. Prazosin dose-dependently blocked the development of methamphetamine conditioned hyperactivity and context-specific sensitization when administered prior to the methamphetamine during the conditioning phase; however nonspecific motor impairments also were observed (Experiment 1). Immediate (Experiment 2), but not the 24-hour delay (Experiment 3), post-session administration of prazosin attenuated the development of methamphetamine conditioned hyperactivity and context-specific sensitization. Nonspecific motor impairments were not observed in these latter experiments. Collectively, these results suggest that the α1-adrenergic receptor mediates the development of methamphetamine-conditioned hyperactivity and context-specific sensitization, perhaps by altering memory consolidation and/or reconsolidation processes. PMID:24487011

  19. Methamphetamine (Meth)

    MedlinePlus

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

  20. Methamphetamine (Meth)

    MedlinePlus

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

  1. 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

  2. Distinct intrinsic functional brain network abnormalities in methamphetamine-dependent patients with and without a history of psychosis.

    PubMed

    Ipser, Jonathan C; Uhlmann, Anne; Taylor, Paul; Harvey, Brian H; Wilson, Don; Stein, Dan J

    2016-12-05

    Chronic methamphetamine use is associated with executive functioning deficits that suggest dysfunctional cognitive control networks (CCNs) in the brain. Likewise, abnormal connectivity between intrinsic CCNs and default mode networks (DMNs) has also been associated with poor cognitive function in clinical populations. Accordingly, we tested the extent to which methamphetamine use predicts abnormal connectivity between these networks, and whether, as predicted, these abnormalities are compounded in patients with a history of methamphetamine-associated psychosis (MAP). Resting-state fMRI data were acquired from 46 methamphetamine-dependent patients [19 with MAP, 27 without (MD)], as well as 26 healthy controls (CTRL). Multivariate network modelling and whole-brain voxel-wise connectivity analyses were conducted to identify group differences in intrinsic connectivity across four cognitive control and three DMN networks identified using an independent components analysis approach (meta-ICA). The relationship of network connectivity and psychotic symptom severity, as well as antipsychotic treatment and methamphetamine use variables, was also investigated. Robust evidence of hyper-connectivity was observed between the right frontoparietal and anterior DMN networks in MAP patients, and 'normalized' with increased duration of treatment with antipsychotics. Attenuation of anticorrelated anterior DMN-dorsal attention network activity was also restricted to this group. Elevated coupling detected in MD participants between anterior and posterior DMN networks became less apparent with increasing duration of abstinence from methamphetamine. In summary, we observed both alterations of RSN connectivity between DMN networks with chronic methamphetamine exposure, as well as DMN-CCN coupling abnormalities consistent with possible MAP-specific frontoparietal deficits in the biasing of task-appropriate network activity. © 2016 Society for the Study of Addiction.

  3. P3a of event-related potential in chronic methamphetamine dependence.

    PubMed

    Iwanami, A; Kuroki, N; Iritani, S; Isono, H; Okajima, Y; Kamijima, K

    1998-12-01

    To investigate the psychophysiological features of methamphetamine (MAP) dependence, we recorded auditory event-related potentials (ERPs) in 15 patients with MAP dependence and in 15 age-matched normal controls. ERPs were recorded during a standard oddball task and a read task similar to those employed by Squires et al. (Squires NK, Squires KC, Hillyard SA [1975] Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroenceph Clin Neurophysiol 38:387-401). The patients with MAP dependence showed reduced P3a amplitude and area in the read task and delayed P3b latency with normal P3b amplitude and area in the oddball task. These results suggest that central noradrenergic dysregulation may persist after the remission of acute psychotic symptoms in MAP psychosis and that chronic MAP dependence would produce impairment of the frontal cortex.

  4. Deterioration of intelligence in methamphetamine-induced psychosis: comparison with alcohol dependence on WAIS-III.

    PubMed

    Lin, Shih-Ku; Huang, Ming-Chy; Lin, Hui-Che; Pan, Chun-Hong

    2010-02-01

    Long-term use of methamphetamine could induce psychosis, but consequences with regards to intelligence have seldom been investigated. Long-term use of alcohol could also result in intellectual deterioration. The IQ of 34 methamphetamine-induced psychosis (MIP) patients (age, 28.7 +/- 6.1 years) and 34 alcohol-dependent (AD) patients (age, 40.7 +/- 7.3 years) was compared using the Chinese version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). The average full-scale IQ, verbal IQ, performance IQ, verbal comprehension index, working memory index, perceptual organization index, and processing speed index was 82.3 +/- 10.8, 84.3 +/- 11.9, 81.9 +/- 12.1, 85.5 +/- 11.9, 84.7 +/- 12.5, 85.4 +/- 13.6, and 78.5 +/- 12.7 in MIP patients and 90.5 +/- 12.0, 95.2 +/- 11.3, 86.0 +/- 13.7, 95.5 +/- 11.0, 87.1 +/- 14.5, 96.2 +/- 13.1, and 84.5 +/- 15.0 in AD patients, respectively. There were six MIP patients (17.6%) whose full-scale IQ was <70 and 13 (38.2%) whose full-scale IQ was <85 and >70, while one AD patient had a full-scale IQ <70 (2.9%) and 10 (22%) had full-scale IQ <85 and >70. Long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration. Intelligence deterioration is more severe in clinical MIP patients than AD patients. Assessment of the mentality of MIP patients is suggested to help with the implementation of rehabilitative programs for these patients.

  5. Frequency of Psychiatric Disorders in Children of Opioid or Methamphetamine-Dependent Patients.

    PubMed

    Parvaresh, Noushin; Mazhari, Shahrzad; Nazari-Noghabi, Maryam

    2015-01-01

    Addiction is one of the main problems of human societies, which is more common in developing countries. In addition, it causes to personal and social problems and family problem. The aim of this study was to examine the prevalence of psychiatric disorders in children 5-15 years old of opioid or methamphetamine dependence patients. For this study, three groups including: (1) children of parents addicted to opium, (2) children of parents addicted to methamphetamine, and (3) control group were examined. Child symptom inventory-4 (CSI-4) questionnaires completed by non-hospitalized guardian and control group; then make interviews with the children by the Kiddie-schedule for affective disorders and schizophrenia (K-SADS). Data were analyzed by chi-square test and ANOVA. Survey showed that the frequency of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), generalized anxiety disorder, obsessive-compulsive disorder, specific phobia (SP), and separation anxiety disorder in children of addicted parents were more than a non-addicted parent. However, there was no significant difference between the two groups in the frequency of conduct disorder, social phobia, and oppositional defiant disorders (ODDs). Parental addiction can lead to an increase in some psychiatric disorders in the children. Therefore follow-up, early diagnosis, treatment, and prevention of these disorders in children of the drug-dependent parent are necessary to reduce health costs and improve the health system.

  6. 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

  7. Methamphetamine produces bidirectional, concentration-dependent effects on dopamine neuron excitability and dopamine-mediated synaptic currents

    PubMed Central

    Branch, Sarah Y.

    2012-01-01

    Amphetamine-like compounds are commonly used to enhance cognition and to treat attention deficit/hyperactivity disorder, but they also function as positive reinforcers and are self-administered at doses far exceeding clinical relevance. Many of these compounds (including methamphetamine) are substrates for dopamine reuptake transporters, elevating extracellular dopamine by inhibiting uptake and promoting reverse transport. This produces an increase in extracellular dopamine that inhibits dopamine neuron firing through autoreceptor activation and consequently blunts phasic dopamine neurotransmission, an important learning signal. However, these mechanisms do not explain the beneficial behavioral effects observed at clinically useful concentrations. In the present study, we have used patch-clamp electrophysiology in slices of mouse midbrain to show that, surprisingly, low concentrations of methamphetamine actually enhance dopamine neurotransmission and increase dopamine neuron firing through a dopamine transporter-mediated excitatory conductance. Both of these effects are reversed by higher concentrations of methamphetamine, which inhibit firing through dopamine D2 autoreceptor activation and decrease the peak amplitude of dopamine-mediated synaptic currents. These competing, concentration-dependent effects of methamphetamine suggest a mechanistic interplay by which lower concentrations of methamphetamine can overcome autoreceptor-mediated inhibition at the soma to increase phasic dopamine transmission. PMID:22592307

  8. THE IMPACT OF CLINICAL AND DEMOGRAPHIC VARIABLES ON COGNITIVE PERFORMANCE IN METHAMPHETAMINE-DEPENDENT INDIVIDUALS IN RURAL SOUTH CAROLINA

    PubMed Central

    Price, KL; DeSantis, SM; Simpson, AN; Tolliver, BK; McRae-Clark, AL; Saladin, ME; Baker, NL; Wagner, MT; Brady, KT

    2013-01-01

    Inconsistencies in reports on methamphetamine (METH) associated cognitive dysfunction may be attributed, at least in part, to the diversity of study sample features (egg, clinical and demographic characteristics). The current study assessed cognitive function in a METH-dependent population from rural South Carolina, and the impact of demographic and clinical characteristics on performance. Seventy-one male (28.2%) and female (71.8%) METH-dependent subjects were administered a battery of neurocognitive tests including the Test of Memory Malingering (TOMM), Shipley Institute of Living Scale, Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Grooved Pegboard Test, California Verbal Learning Test (CVLT), and Wisconsin Card Sorting Test (WCST). Demographic and clinical characteristics (egg, gender, frequency of METH use) were examined as predictors of performance. Subjects scored significantly lower than expected on one test of attention and one of fine motor function, but performed adequately on all other tests. There were no predictors of performance on attention; however, more frequent METH use was associated with better performance for males and worse for females on fine motor skills. The METH-dependent individuals in this population exhibit very limited cognitive impairment. The marked differences in education, Intellectual Quotient (IQ), and gender in our sample when compared to the published literature may contribute to these findings. Characterization of the impact of clinical and/or demographic features on cognitive deficits could be important in guiding the development of treatment interventions. PMID:21838844

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2010-10-01

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

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

    PubMed Central

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

    2013-01-01

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

  12. 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. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  13. 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

  14. A randomized, double-blind, placebo-controlled trial of citicoline for bipolar and unipolar depression and methamphetamine dependence.

    PubMed

    Brown, E Sherwood; Gabrielson, Barry

    2012-12-20

    Methamphetamine use disorders are common and severe problems. Persons with mood disorders, particularly bipolar disorder, have high rates of substance use disorders. We previously reported promising findings on drug use, memory and study retention in patients with a history of mania and cocaine dependence given the nutritional supplement citicoline. In the current proof-of-concept study, we examined citicoline in bipolar or unipolar depression and methamphetamine dependence. Sixty adults with bipolar depression or major depressive disorder and methamphetamine dependence were randomized to citicoline (2000mg/day) or placebo for 12 weeks. Mood was assessed using Inventory of Depressive Symptomatology-Clinician Version (IDS-C), and cognition with the Hopkins Auditory Verbal Learning Test (HVLT). Drug use was assessed by urine drug screens. An ANCOVA of the intent-to-treat sample showed that those receiving citicoline (n=28) had a statistically significantly greater improvement in IDS-C scores than those receiving placebo (n=20). Survival in the study was significantly longer and completion rates significantly greater with citicoline than placebo. No significant differences were observed in memory or methamphetamine use. Citicoline was well tolerated. Sample heterogeneity and small sample size were limitations. To our knowledge this is the first placebo-controlled trial in a dual diagnosis sample with methamphetamine use disorders. Findings suggest that citicoline may have antidepressant properties in this population. Greater treatment retention with citicoline is also noteworthy in a patient population with substance dependence. Larger trials targeting depressive symptoms and treatment retention seem warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-07-22

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

  16. Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study.

    PubMed

    Ernst, T; Chang, L; Leonido-Yee, M; Speck, O

    2000-03-28

    To determine whether proton MRS (1H MRS) can detect long-term metabolite abnormalities in abstinent methamphetamine users. Methamphetamine is toxic to dopaminergic and serotonergic neurons in rodents; however, little data are available on the toxic effects of methamphetamine on the human brain. 1H MRS was performed in 26 abstinent methamphetamine abusers with a history of methamphetamine dependence (median total cumulative lifetime exposure, 3,640 g; median recency of last methamphetamine use, 4.25 months) and 24 healthy subjects without a history of drug abuse. Cerebral metabolite concentrations on 1H MRS were measured in the frontal cortex, frontal white matter, and basal ganglia. The concentration of N-acetylaspartate ([NA]), a neuronal marker, was reduced significantly (-5 to -6%) in the basal ganglia and frontal white matter of methamphetamine users compared with control subjects. The frontal white matter [NA] correlated inversely with the logarithm of the lifetime methamphetamine use. The methamphetamine users also showed significantly reduced total creatine in the basal ganglia (-8%), and increased choline-containing compounds ([CHO], +13%) and myo-inositol ([MI], +11%) in the frontal grey matter. The reduced [NA] on 1H MRS provides evidence for long-term neuronal damage in abstinent methamphetamine users.

  17. Methamphetamine and Paranoia: The Methamphetamine Experience Questionnaire

    PubMed Central

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

    2011-01-01

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

  18. Methamphetamine and paranoia: the methamphetamine experience questionnaire.

    PubMed

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

    2010-01-01

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

  19. Eight Weeks of Exercise Training Improves Fitness Measures in Methamphetamine-Dependent Individuals in Residential Treatment

    PubMed Central

    Dolezal, Brett A.; Chudzynski, Joy; Storer, Thomas W.; Abrazado, Marlon; Penate, Jose; Mooney, Larissa; Dickerson, Daniel; Rawson, Richard A.; Cooper, Christopher B.

    2013-01-01

    Objectives Physical exercise has been shown to benefit diverse medical and behavioral conditions. This study assesses the feasibility and efficacy of an 8-week endurance and resistance training program on fitness measures in individuals undergoing residential treatment for methamphetamine (MA) dependence. Methods A total of 39 MA-dependent individuals were randomized to 3 days/week of exercise training (ET, n=15) or health education without training (EA, n=14) over 8 weeks. Aerobic performance (VO2max) was measured by indirect calorimetry, body composition by skinfolds, muscle strength by 1-repetition maximum (1-RM) and endurance at 85% of 1-RM for both leg press (LP) and chest press (CP). Results A total of 29 individuals completed the study for a 74% adherence rate. Baseline characteristics (mean±SD) were balanced between groups: age 31±7 years; height=1.74±0.07 m; weight 82.0±15.0 kg. The ET group significantly improved VO2max by 0.63±0.22 L/min (+21%), LP strength by 24.4±5.6 kg (+40%) and CP strength by 20.6±5.7 kg (+49%). The ET group increased LP and CP endurance by 120% and 96%, respectively and showed significant reductions in body weight of 1.7±2.4 kg (−2%), % body fat of 2.8±1.3% (−15%) and fat weight 2.8±1.8 kg (−18%). All changes were significant (P<0.001) for ET, and no changes were seen for the EA group. Conclusions Individuals recovering from methamphetamine dependence showed substantial improvements in aerobic exercise performance, muscle strength and endurance, and body composition with exercise training. These findings demonstrate the feasibility of an exercise training intervention in these participants and also show excellent responsiveness to the exercise stimulus resulting in physiological changes that might enhance recovery from drug dependency. PMID:23552821

  20. A tale of two stimulants: mentholated cigarettes may play a role in cocaine, but not methamphetamine, dependence

    PubMed Central

    Winhusen, Theresa M.; Adinoff, Bryon; Lewis, Daniel F.; Brigham, Gregory S.; Gardin, John G.; Sonne, Susan C.; Theobald, Jeff; Ghitza, Udi

    2013-01-01

    Background Research suggests that mentholated cigarettes may play a role in cocaine dependence. The purpose of the present study was to expand upon the research on mentholated cigarettes and cocaine dependence and to evaluate the role of mentholated cigarettes in methamphetamine dependence. Methods Secondary analysis of a multisite, randomized trial evaluating the impact of smoking-cessation treatment in stimulant-dependent outpatients (N=538). Participants' reasons for concurrent use of cigarettes and illicit stimulants were assessed via self-report. Stimulant-abstinence was measured by self-report and urine drug screens. Smoking cessation was assessed via self-report and carbon monoxide levels. Results Of the 301 cocaine-dependent participants, 201 (67%) were menthol and 100 (33%) were non-menthol cigarette smokers. Cocaine-dependent participants who smoked menthol, compared to non-menthol, cigarettes were significantly more likely to report that cigarettes prolong their cocaine high (X2(1)=16.3, p<.0001, OR=3.58 [95% CI: 1.88–6.79]) and were less likely to be stimulant abstinent during active treatment (W=3.6, p<0.001, d=.39 [95% CI: 0.16–0.62]), at 3-month follow-up (X2(1)=14.4 p<0.001, OR=.32 [95% CI: 0.17–0.58]), and at 6-month follow-up (X2(1)=4.6, p=0.03, OR=.53 [95% CI: 0.29–0.95]). No parallel differences were found between menthol and non-menthol methamphetamine-dependent smokers. The prevalence of Caucasian menthol smokers was significantly greater in the cocaine-dependent participants (37.2%) than in the methamphetamine-dependent participants (17.61%), (X2(1)=14.4 p<.001, OR=2.77 [95% CI:1.62–4.73]). Smoking cessation was not significantly associated with cigarette type for either cocaine- or methamphetamine-dependent participants. Conclusions The present results suggest that mentholated cigarettes play a role in cocaine, but not methamphetamine, dependence. PMID:24075226

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

  4. 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

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

    PubMed Central

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

    2015-01-01

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

  6. Predictors of depression outcomes among abstinent methamphetamine-dependent individuals exposed to an exercise intervention.

    PubMed

    Haglund, Margaret; Ang, Alfonso; Mooney, Larissa; Gonzales, Rachel; Chudzynski, Joy; Cooper, Christopher B; Dolezal, Brett A; Gitlin, Michael; Rawson, Richard A

    2015-04-01

    This paper expands on a study investigating depression outcomes in response to an 8-week exercise intervention among methamphetamine (MA) dependent individuals in early recovery. A total of 135 MA-dependent individuals enrolled in residential treatment were randomly assigned to either a structured exercise intervention or a structured health education control group. Both groups were similar in format: 60-minute sessions, offered three times a week over an 8-week study period. Results showed that at the 8-week trial endpoint, participants randomized to the exercise intervention showed significantly greater reduction in depression symptom scores than participants randomized to the health education group, and that participants who attended the greatest number of exercise sessions derived the greatest benefit. This paper further analyzes study data to uncover individual predictors of depression response to exercise and finds that among participants randomized to exercise treatment, individuals with the most severe medical, psychiatric, and addiction disease burden at baseline showed the most significant improvement in depressive symptoms by study endpoint. Our findings suggest that exercise in moderate dose is effective at treating depressive symptoms in individuals in early recovery from addiction, and furthermore, that treatment with exercise appears to be particularly beneficial to individuals who suffer from severe medical, psychiatric, and addictive disorders. © American Academy of Addiction Psychiatry.

  7. Role of microsomal epoxide hydrolase in methamphetamine-induced drug dependence in mice.

    PubMed

    Shin, Eun-Joo; Bing, Guoying; Chae, Jong Seok; Kim, Tae Woo; Bach, Jae-Hyung; Park, Dae Hun; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2009-12-01

    Microsomal epoxide hydrolase (mEH) and cytochrome P-450 (CYP) ensure the rapid detoxification of epoxides generated during the oxidative metabolism of xenobiotics. Although CYP has been demonstrated to modulate methamphetamine (METH)-induced behavioral effects, little is known about the role of the mEH gene on these effects. We examined the role of mEH gene expression in METH-induced conditioned place preference and behavioral sensitization by using mEH(-/-) and wild-type (WT) mice. Extracellular dopamine (DA) levels and DA uptake into synaptosomes were assessed by using an in vivo microdialysis and [(3)H]DA uptake assay. We applied double-label immunocytochemistry to characterize mEH-positive cellular types. METH-induced behavioral responses paralleled striatal c-Fos-like immunoreactivity. METH treatment resulted in increased extracellular DA levels in the nucleus accumbens but decreased synaptosomal DA uptake in the striatum. These behavioral and neurochemical changes were more pronounced in the mEH(-/-) mice than in WT mice. In WT mice, mEH-like immunoreactivity was expressed in astrocytes labeled by GFAP or S100B after METH treatment. The results suggest that epoxide intermediates mediate METH drug dependence and that astrocytic reactions of mEH protein are important in the endogenous modulation in response to METH drug dependence. Copyright 2009 Wiley-Liss, Inc.

  8. An open-label pilot study of risperidone in the treatment of methamphetamine dependence.

    PubMed

    Meredith, Charles W; Jaffe, Craig; Yanasak, Elisia; Cherrier, Monique; Saxon, Andrew J

    2007-06-01

    Psychopharmacological treatments for methamphetamine (MA) dependence have questionable efficacy. Open-label risperidone was evaluated in veterans seeking MA dependence treatment. Participants (N = 11) received four weeks of risperidone. They provided weekly self-reports of substance use, urine drug screens, and adverse effects. Neuropsychological assessments and psychiatric symptomatology (Brief Symptom Inventory; BSI) were measured at baseline and follow-up. The eight completers had an average risperidone dose of 3.6 mg/day and decreased days of MA use during the trial from a mean of 13.0 (SD = 6.5) in the 30 days prior to starting risperidone to a mean of 0.125 (SD = 0.4; t = 5.7, p = .001), When measured over time, fine motor function (Grooved Peg Board Dominant Hand) was the only neuropsychological domain to improve significantly. No other domain changed significantly from baseline to follow-up among study completers. BSI data were converted to demographically corrected T-scores utilizing appropriate normative data (mean = 50, SD = 10). BSI somatization T-scores declined from a mean of 59.0 (SD = 8.4) to 51.8 (SD = 8.3; t = 2.7, p <.05), and positive symptom distress declined from a mean of 52.8 (SD =8.0) to 41.7 (SD = 8.6; t= 3.0, p <.05). Risperidone was well tolerated and associated with decreased MA use.

  9. Mouse Strain- and Age-dependent Effects of Binge Methamphetamine on Dopaminergic Signaling

    PubMed Central

    Good, Renee L.; Liang, Li-Ping; Patel, Manisha; Radcliffe, Richard A.

    2011-01-01

    We have shown that a single “binge” dose of methamphetamine (Meth) in mice has long-lasting effects on open-field behavior dependent on mouse strain and age. Here we further investigated the impact of genotype and age on tyrosine hydroxylase (TH) loss and dopamine (DA) metabolism due to a high binge dose of Meth (4 × 5 mg/kg × 2 hours × 2 days). Administration of high dose Meth or saline (Sal) to adolescent (PND 40) and adult (PND 80) C57BL/6 (B6), DBA/2 (DBA), and 129S6SvEv/Tac (129) mice was followed by a 1 mg/kg Meth or Sal (control) challenge 40 days later. Striatal and prefrontal cortex tissues were collected one hour following the challenge. Meth-pretreated adolescent B6 and DBA mice exhibited losses in striatal DA concentrations; DBA adolescents also showed losses in striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and increased DA turnover. Pre-exposed B6 and 129 adults demonstrated significant decreases in striatal DA, DOPAC, and increased DA turnover; DBA adults showed significant losses in striatal DA and increased DA turnover. 129 and DBA adults exhibited increases and decreases, respectively, in prefrontal cortex DA. Adult pretreated B6 mice produced significant losses in striatal TH. The results again show age and genotype dependent differences in Meth-induced DA alterations. PMID:21798282

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

    PubMed

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

    2009-08-01

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

  11. 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

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

    PubMed

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

    2017-03-21

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

  13. 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.

  14. A randomized, placebo-controlled trial of aripiprazole for the treatment of methamphetamine dependence and associated psychosis.

    PubMed

    Sulaiman, Ahmad Hatim; Gill, Jesjeet Singh; Said, Mas Ayu; Zainal, Nor Zuraida; Hussein, Habil Mohamad; Guan, Ng Chong

    2013-06-01

    The objectives of this study were to determine the efficacy and safety of aripiprazole for treatment of psychosis, retention and abstinence in patients with methamphetamine dependence. This was a double-blind study where 37 methamphetamine dependent patients with history of psychosis were randomly assigned to receive aripiprazole (5-10 mg daily, N = 19) or placebo (N = 18) for 8 weeks. Follow-up evaluation was scheduled on day 7, 14, 28, 42 day 56 after enrolment. Participants on aripiprazole were retained significantly longer in treatment (48.7 days, SD =4.0) compared to placebo (37.1 days, SD =5.0). The Kaplan-Meier survival analysis showed that participants on aripiprazole were less likely to drop out of the study than the placebo group (P =0.02, χ(2) =5.3). Psychotic symptoms significantly decreased among those on aripiprazole as compared to placebo (P < 0.05). However, no statistically significance was found between the two groups in maintaining abstinence (generalised estimation equation (GEE) analysis, P = 0.41). No serious adverse events were reported in either group. Aripiprazole was no more effective than placebo in maintaining abstinence from methamphetamine use. However, it facilitated treatment retention and reduced the severity of psychotic symptoms. Aripiprazole was found to be generally safe and well tolerated.

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

    PubMed

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

    2014-11-01

    Although the Barratt Impulsiveness Scale (BIS; Patton, Stanford, & Barratt, 1995) is a widely-used self-report measure of impulsivity, there have been numerous questions about the invariance of the factor structure across clinical populations (Haden & Shiva, 2008, 2009; Ireland & Archer, 2008). The goal of this article is to examine the factor structure of the BIS among a sample consisting of three populations exhibiting addictive behaviors and impulsivity: pathological gamblers, hypersexual patients, and individuals seeking treatment for methamphetamine dependence to determine if modification to the existing factors might improve the psychometric properties of the BIS. The current study found that the factor structure of the BIS does not replicate in this sample and instead produces a 12-item three-factor solution consisting of motor-impulsiveness (5 items), non-planning impulsiveness (3 items), and immediacy impulsiveness (4 items). The clinical utility of the BIS in this population is questionable. The authors suggest future studies to investigate comparisons with this modified version of the BIS and other impulsivity scales such as the UPPS-P Impulsive Behavior Scale in clinical populations when assessing disposition toward rash action. Copyright © 2013. Published by Elsevier Ltd.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Rostami, R; Dehghani-Arani, F

    2015-09-01

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

  18. 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.

  19. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Acevedo, Summer F; de Esch, Iwan J P; Raber, Jacob

    2007-03-01

    As prenatal methamphetamine (MA) exposure results in long-term hippocampus-dependent cognitive deficits, the increased MA use in women of childbearing age is of great concern. As mice are most commonly used in genetic models, we started to study the potential effects of neonatal MA exposure in female and male mice on brain function 3 months later. As histamine (HA) might mediate some effects of MA in adulthood, we also tested whether in neonates HA might mediate the long-term effects of MA using HA H(3) receptor agonists and antagonists. Stimulation of HA H(3) receptors by H(3) agonists inhibits HA synthesis and release, whereas inhibition of H(3) receptors by H(3) receptor antagonists increases HA release. MA (5 mg/kg), the H(3) receptor antagonist thioperamide (5 mg/kg), and the H(3) receptor agonist immepip (5 mg/kg) alone or in the presence of MA (5 mg/kg) were administered once daily from postnatal days 11 to 20 and the mice were tested at 3 months of age. Here we show that in mice exposure to MA early in life causes sex-dependent impairments in object recognition, spatial learning, and memory in the water maze, and pre-pulse inhibition in adulthood. HA mediates these impairments. Increasing HA release mimicked, whereas inhibiting HA release blocked the long-term detrimental MA effects. This model could be used to determine the role of genetic and environmental factors in MA-dependent cognitive impairments and to develop therapeutic strategies to inhibit them.

  2. 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.

  3. Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence

    PubMed Central

    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. White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

    PubMed

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

    2016-06-01

    Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Preliminary Psychometric Evaluation of the Hamilton Depression Rating Scale in Methamphetamine Dependence.

    PubMed

    Hellem, Tracy; Scholl, Lindsay; Ferguson, Hayden; McGlade, Erin; Yurgelun-Todd, Deborah; Renshaw, Perry; Hildreth, Laura

    2017-08-18

    The purpose of this study was to test the initial psychometric properties of the 17-item Hamilton Depression Rating Scale (HAM-D) in individuals with and without major depressive disorder who use methamphetamine. We used data from two completed studies and two ongoing clinical trials. The HAM-D has well established reliability and validity in a variety of populations. However, there are no published reports of reliability and validity of the HAM-D in a methamphetamine using population. HAM-D and depression status data were extracted from four separate studies for this psychometric assessment. Using these data, we evaluated three measures of construct validity: internal consistency, contrasted groups validity and factorial validity. We found potential concerns with the construct validity of the HAM-D in users of methamphetamine. Intercorrelations between items were primarily less than 0.20 and the Cronbach's alpha value in this sample was 0.58 indicating potential issues with internal consistency. The results of a two sample t-tests suggest concerns with contrasted group validity, as no significant difference in average scores were found for nine items. Consistent with previous studies, a principal component analysis indicates that the HAM-D is multidimensional. The 17-item HAM-D might not reliably and validly measure depression severity in a methamphetamine using population. Given our small sample, additional research is needed, though, to further test the psychometric properties of the HAM-D in individuals who use methamphetamine.

  6. Antisocial Personality Disorder Predicts Methamphetamine Treatment Outcomes in Homeless, Substance-dependent Men Who Have Sex with Men

    PubMed Central

    Fletcher, Jesse B.; Reback, Cathy J.

    2013-01-01

    One-hundred-thirty-one homeless, substance-dependent MSM were enrolled in a randomized controlled trial to assess the efficacy of a contingency management (CM) intervention for reducing substance use and increasing healthy behavior. Participants were randomized into conditions that either provided additional rewards for substance abstinence and/or health-promoting/prosocial behaviors (“CM-Full”; n = 64) or for study compliance and attendance only (“CM-Lite”; n = 67). The purpose of this secondary analysis was to determine the affect of ASPD status on two primary study outcomes: methamphetamine abstinence, and engagement in prosocial/health-promoting behavior. Analyses revealed that individuals with ASPD provided more methamphetamine-negative urine samples (37.5%) than participants without ASPD (30.6%). When controlling for participant sociodemographics and condition assignment, the magnitude of this predicted difference increases to 10% and reached statistical significance (p < .05). On average, participants with ASPD earned fewer vouchers for health-promoting/prosocial behaviors than participants without ASPD ($10.21 [SD=$7.02] vs. $18.38 [SD=$13.60]; p < .01). Participants with ASPD displayed superior methamphetamine abstinence outcomes regardless of CM schedule; even with potentially unlimited positive reinforcement, individuals with ASPD displayed suboptimal outcomes in achieving health-promoting/prosocial behaviors. PMID:23579078

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

    PubMed

    Fletcher, Jesse B; Reback, Cathy J

    2013-09-01

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

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

    PubMed Central

    Acevedo, Summer F.; Raber, Jacob

    2011-01-01

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

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

    PubMed

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

    2011-03-30

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

  10. 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…

  11. 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…

  12. Open-label study of a proprietary treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in methamphetamine dependence.

    PubMed

    Urschel, Harold C; Hanselka, Larry L; Gromov, Irin; White, Lenae; Baron, Michael

    2007-10-01

    To evaluate the safety and efficacy of the pharmacological component of a proprietary medical treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in adults who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for methamphetamine dependence. A prospective, open-label, single-group study of the medication portion of a proprietary treatment program for methamphetamine dependence was conducted from July 1, 2005, to May 10, 2006, at Research Across America, an outpatient private, for-profit, clinical research company in Dallas, TX. In the study, flumazenil, hydroxyzine, and gabapentin, all of which were approved by the US Food and Drug Administration for indications other than drug dependence, were used off-label for the treatment of methamphetamine dependence. Fifty persons who had used methamphetamine within 7 days of study entry were enrolled and received the treatment. Treatment lasted 4 weeks, followed by 8 weeks of weekly follow-up visits to monitor for methamphetamine use via urine drug tests and self-reporting. Participant retention was higher than expected, with 85% of participants completing the program. Significant decrease in methamphetamine use (P<.001) was noted at 84 days after vs 90 days before treatment. If missing data are counted as days of methamphetamine use, a 47% reduction in use was observed for the entire sample (P<.001) and a 65% reduction for the 36 who completed the 8-week evaluation phase (P<.001). Urine test results and self-reported use were positively correlated (Pearson r=0.72, P<.001). The frequency of cravings was reduced on average by 66% (P<.001), with 30 of 31 (97%) of the 36 who completed the study reporting reduction in cravings. Substantial reductions in methamphetamine cravings and use were observed in all phases of treatment, and the retention rate of participants was high. These findings suggest that the efficacy of the medications and of the

  13. Methamphetamine and ethanol interactions in humans.

    PubMed

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

    1995-05-01

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

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

    PubMed

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

    2013-04-01

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

  15. Extended-release methylphenidate for treatment of amphetamine/methamphetamine dependence: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Miles, S Wayne; Sheridan, Janie; Russell, Bruce; Kydd, Rob; Wheeler, Amanda; Walters, Carina; Gamble, Greg; Hardley, Peta; Jensen, Maree; Kuoppasalmi, Kimmo; Tuomola, Pekka; Föhr, Jaana; Kuikanmäki, Outi; Vorma, Helena; Salokangas, Raimo; Mikkonen, Antti; Kallio, Mika; Kauhanen, Jussi; Kiviniemi, Vesa; Tiihonen, Jari

    2013-07-01

    To assess the efficacy of methylphenidate as a substitution therapy for amphetamine/methamphetamine dependence in Finland and New Zealand. Parallel-group, double-blind, randomized placebo-controlled trial. Out-patient care. Amphetamine-/methamphetamine-dependent, aged 16-65 years. The primary outcome measure was presence/absence of amphetamine/methamphetamine in urine samples collected twice weekly. Secondary measures included treatment adherence, alterations in craving scores and self-reported use. Primary analysis was by intention-to-treat (ITT). The study drug, methylphenidate (as Concerta(®) ), was up-titrated over 2 weeks to a maximum dose of 54 mg daily and continued for a further 20 weeks. Doses were given under daily supervision at the clinics. Seventy-nine participants were randomized (40 methylphenidate; 39 placebo); 76 received allocated treatment and 27 completed the trial. ITT analysis (n = 78) showed no statistically significant difference in the percentage of positive urines between the methylphenidate and placebo arms (odds ratio: 0.95, 95% confidence interval: 0.83-1.08). However, there was a significant difference (P < 0.05) between the active and placebo arms in retention, the placebo arm displaying a significantly lower retention from 6 weeks that persisted until the end of the trial. The trial failed to replicate earlier findings suggesting that methylphenidate was superior to placebo. The low retention rate confounded the ability to draw firm conclusions about efficacy. The higher retention rate was observed in the methylphenidate arm. Any replication of this work would need to consider alternatives to the rigid clinic attendance criteria, and consider an increased dose. © 2013 The Authors, Addiction © 2013 Society for the Study of Addiction.

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

    PubMed

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

    2015-10-01

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

  17. 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.

  18. 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

  19. Increased prevalence of self-reported psychotic illness predicted by crystal methamphetamine use: Evidence from a high-risk population.

    PubMed

    Lappin, Julia M; Roxburgh, Amanda; Kaye, Sharlene; Chalmers, Jenny; Sara, Grant; Dobbins, Timothy; Burns, Lucinda; Farrell, Michael

    2016-12-01

    The potential of methamphetamine, and high-potency crystal methamphetamine in particular, to precipitate psychotic symptoms and psychotic illness is the subject of much speculation internationally. Established psychotic illness is disabling for individuals and costly to society. The aim of this study was to investigate whether use of crystal methamphetamine was associated with greater prevalence of self-reported psychotic illness, compared to use of other forms of methamphetamine. The sample comprised participants interviewed as part of an annual cross-sectional survey of Australian people who inject drugs. Comparisons were made between groups according to the nature of their methamphetamine use: crystal methamphetamine or other forms of methamphetamine. Self-reported diagnoses of psychotic illness and other mental health problems were compared between groups. Predictors of self-reported psychotic illness were examined using multivariable logistic regression analyses. Self-reported psychotic illness was highly prevalent among users of crystal methamphetamine (12.0%), and significantly more so than among users of other forms of methamphetamine (3.9%) (OR=3.36; CI: 1.03-10.97). Significant predictors of self-reported psychosis in the cohort were: use of crystal methamphetamine; dependent use; lack of education beyond high school; and younger age. Highly increased prevalence of self-reported psychotic illness is associated with use of high-potency crystal methamphetamine in people who inject drugs, particularly where there is dependent use. There is an urgent need to develop effective interventions for dependent crystal methamphetamine use; and a need to monitor for symptoms of psychotic illness in drug-using populations. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  1. Neuroimmune Basis of Methamphetamine Toxicity

    PubMed Central

    Loftis, Jennifer M.; Janowsky, Aaron

    2015-01-01

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

  2. Neuroimmune basis of methamphetamine toxicity.

    PubMed

    Loftis, Jennifer M; Janowsky, Aaron

    2014-01-01

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

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

    PubMed

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

    2016-02-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

  4. Visual information processing in recently abstaining methamphetamine-dependent individuals: evoked potentials study.

    PubMed

    Kremlácek, Jan; Hosák, Ladislav; Kuba, Miroslav; Libiger, Jan; Cízek, Jirí

    2008-11-01

    Methamphetamine (MAP) is an indirect dopamine agonist that can temporarily increase cognitive performance. However, its long-term abuse may cause dopamine depletion and consequent cognitive and attentional impairment. The worsening of visual functions in Parkinson's disease and their improvement after levodopa administration implicates the role of dopamine in the physiology of vision. This provides the rationale for the investigation of visual functions in abstaining MAP abusers. We investigated changes in visually evoked potentials (VEPs) to pattern-reversal and motion-onset stimuli. Such changes serve as indices of visual information processing in the primary and associative areas in a group of recently abstaining MAP abusers (5 females, 18 males, MAP abuse 5.3 +/- 2.8 years) and in 23 age- and gender-paired controls. We did not find differences between the groups in visual acuity. In the group of MAP abusers we observed an attenuation of the early responses around 80 ms and a prolongation of the P1 peak latency after the reversal of high spatial frequency checkerboards (10 and 20 arcmin checks). Furthermore, an attenuation of the latter positive response (170-250 ms) was observed among all the stimuli in parieto-frontal derivations for the MAP abusers. This is the first report suggesting a slowing and attenuation of VEP responses during visual processing in abstaining methamphetamine abusers.

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

    PubMed

    Xi, Jinlei; Kruzich, Paul J

    2007-05-01

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

  6. Methamphetamine abuse.

    PubMed

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

    2007-10-15

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

  7. [Bio-Psycho-Social Characteristics and Therapeutic Aspects of Methamphetamine-Dependent Women - Gender Specific Results of a Systematic Literature Search].

    PubMed

    Neumann, Stefanie; Soyka, Michael; Franke, Andreas G

    2017-08-24

    Subject Compared to other illicit drugs Methamphetamine (MethA) is used more frequently by women than by men. Assuming the biopsychosocial etiology model, the dependency is based on several factors in which women and men differ significantly. Systematic gender-differentiated knowledge is missing until today. Method Based on a database research (PUBMED) the review examines biological, social and psychological as well as therapeutic aspects in MethA-dependent women. Results MethA-induced cognitive disturbance appear to have severer manifestations in women than in men. MethA-addicted women's lifestyle is often characterized by active and passive (sexualized) violence. They show an increased risk behavior; i. e. unprotected sexual intercourse with several partners. Their psychological comorbidities seem to be more pronounced and especially affect anxiety disorders and depressive syndromes. Conclusion and clinical relevance In women, abuse and dependence of MethA are determined by psychological as well as social factors. However, further research is needed to improve prevention, counseling and therapy. © Georg Thieme Verlag KG Stuttgart · New York.

  8. 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

  9. Methamphetamine induces the release of endothelin.

    PubMed

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

    2016-02-01

    Methamphetamine is a potent psychostimulant drug of abuse that increases release and blocks reuptake of dopamine, producing intense euphoria, factors that may contribute to its widespread abuse. It also produces severe neurotoxicity resulting from oxidative stress, DNA damage, blood-brain barrier disruption, microgliosis, and mitochondrial dysfunction. Intracerebral hemorrhagic and ischemic stroke have been reported after intravenous and oral abuse of methamphetamine. Several studies have shown that methamphetamine causes vasoconstriction of vessels. This study investigates the effect of methamphetamine on endothelin-1 (ET-1) release in mouse brain endothelial cells by ELISA. ET-1 transcription as well as endothelial nitric oxide synthase (eNOS) activation and transcription were measured following methamphetamine treatment. We also examine the effect of methamphetamine on isolated cerebral arteriolar vessels from C57BL/6 mice. Penetrating middle cerebral arterioles were cannulated at both ends with a micropipette system. Methamphetamine was applied extraluminally, and the vascular response was investigated. Methamphetamine treatment of mouse brain endothelial cells resulted in ET-1 release and a transient increase in ET-1 message. The activity and transcription of eNOS were only slightly enhanced after 24 hr of treatment with methamphetamine. In addition, methamphetamine caused significant vasoconstriction of isolated mouse intracerebral arterioles. The vasoconstrictive effect of methamphetamine was attenuated by coapplication of the endothelin receptor antagonist PD145065. These findings suggest that vasoconstriction induced by methamphetamine is mediated through the endothelin receptor and may involve an endothelin-dependent pathway. © 2015 Wiley Periodicals, Inc.

  10. Necroptosis contributes to methamphetamine-induced cytotoxicity in rat cortical neurons.

    PubMed

    Xiong, Kun; Liao, Huidan; Long, Lingling; Ding, Yanjun; Huang, Jufang; Yan, Jie

    2016-09-01

    Necroptosis, a programmed necrosis, is involved in various types of neurodegenerative diseases. In this study, we investigated whether necroptosis contributed to neuronal damage in a methamphetamine injury model. Primary cultures of embryonic cortical neurons from Sprague-Dawley rats were subjected to different doses of methamphetamine with/without pre-treatment with a specific necroptosis inhibitor, Necrostatin-1. Necrosis was assessed by determining lactate dehydrogenase release and by Annexin V/propidium iodide double staining, while the neuronal ultra-structure was examined by electron microscopy. Tumor necrosis factor-α protein levels were determined by enzyme-linked immunosorbent assay. At early stages (12h) of post-treatment with methamphetamine, significant necrosis occurred and the viability of neurons decreased in a dose- and time-dependent manner in this model of acute neuronal injury. Pretreatment with Necrostatin-1 led to significant neuronal preservation compared with the methamphetamine-treated groups. Furthermore, tumor necrosis factor-α expression increased in a dose-dependent manner following methamphetamine exposure. Methamphetamine induced necrosis in rat cortical neurons in vitro, both time and dose dependently, and necroptosis may be an important newly identified mode of cortical neuronal death caused by single high-dose methamphetamine administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Emotion Dysregulation and Amygdala Dopamine D2-type Receptor Availability in Methamphetamine Users

    PubMed Central

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

    2016-01-01

    Background Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM-IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala. Method Ninety-four methamphetamine-using and 102 healthy-control subjects completed the Difficulties in Emotion Regulation Scale (DERS); 33 of those who used methamphetamine completed the Addiction Severity Index (ASI). A subset of 27 methamphetamine-group and 20 control-group subjects completed positron emission tomography with [18F]fallypride to assay amygdala D2-type dopamine receptor availability, measured as binding potential (BPND). Results The methamphetamine group scored higher than the control group on the DERS total score (p < 0.001), with DERS total score positively correlated with the Drug Composite Score on the ASI (p = 0.02) in the methamphetamine group. The DERS total score was positively correlated with amygdala BPND in both groups and the combined group of participants (combined: r = 0.331, p = 0.02), and the groups did not differ in this relationship. Conclusion These findings highlight problems with emotion regulation linked to methamphetamine use, possibly contributing to personal and interpersonal behavioral problems. They also suggest that D2-type dopamine receptors in the amygdala contribute to emotion regulation in both healthy and methamphetamine-using subjects. PMID:26880595

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

    PubMed

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

    2016-04-01

    Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM-IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala. Ninety-four methamphetamine-using and 102 healthy-control subjects completed the Difficulties in Emotion Regulation Scale (DERS); 33 of those who used methamphetamine completed the Addiction Severity Index (ASI). A subset of 27 methamphetamine-group and 20 control-group subjects completed positron emission tomography with [(18)F]fallypride to assay amygdala D2-type dopamine receptor availability, measured as binding potential (BPND). The methamphetamine group scored higher than the control group on the DERS total score (p<0.001), with DERS total score positively correlated with the Drug Composite Score on the ASI (p=0.02) in the methamphetamine group. The DERS total score was positively correlated with amygdala BPND in both groups and the combined group of participants (combined: r=0.331, p=0.02), and the groups did not differ in this relationship. These findings highlight problems with emotion regulation linked to methamphetamine use, possibly contributing to personal and interpersonal behavioral problems. They also suggest that D2-type dopamine receptors in the amygdala contribute to emotion regulation in both healthy and methamphetamine-using subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Methamphetamine psychosis: epidemiology and management.

    PubMed

    Glasner-Edwards, Suzette; Mooney, Larissa J

    2014-12-01

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

  14. Methamphetamine Psychosis: Epidemiology and Management

    PubMed Central

    Glasner-Edwards, Suzette; Mooney, Larissa J.

    2016-01-01

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

  15. 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

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

    2016-01-01

    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. 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. 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, there was no significant

  16. Fine-grain analysis of the treatment effect of topiramate on methamphetamine addiction with latent variable analysis.

    PubMed

    Ma, Jennie Z; Johnson, Bankole A; Yu, Elmer; Weiss, David; McSherry, Frances; Saadvandi, Jim; Iturriaga, Erin; Ait-Daoud, Nassima; Rawson, Richard A; Hrymoc, Mark; Campbell, Jan; Gorodetzky, Charles; Haning, William; Carlton, Barry; Mawhinney, Joseph; Weis, Dennis; McCann, Michael; Pham, Tony; Stock, Christopher; Dickinson, Ruth; Elkashef, Ahmed; Li, Ming D

    2013-06-01

    As reported previously, 140 methamphetamine-dependent participants at eight medical centers in the U.S. were assigned randomly to receive topiramate (N=69) or placebo (N=71) in a 13-week clinical trial. The study found that topiramate did not appear to reduce methamphetamine use significantly for the primary outcome (i.e., weekly abstinence from methamphetamine in weeks 6-12). Given that the treatment responses varied considerably among subjects, the objective of this study was to identify the heterogeneous treatment effect of topiramate and determine whether topiramate could reduce methamphetamine use effectively in a subgroup of subjects. Latent variable analysis was used for the primary and secondary outcomes during weeks 6-12 and 1-12, adjusting for age, sex, and ethnicity. Our analysis of the primary outcome identified 30 subjects as responders, who either reduced methamphetamine use consistently over time or achieved abstinence. Moreover, topiramate recipients had a significantly steeper slope in methamphetamine reduction and accelerated to abstinence faster than placebo recipients. For the secondary outcomes in weeks 6-12, we identified 40 subjects as responders (who had significant reductions in methamphetamine use) and 65 as non-responders; topiramate recipients were more than twice as likely as placebo recipients to be responders (odds ratio=2.67; p=0.019). Separate analyses of the outcomes during weeks 1-12 yielded similar results. Methamphetamine users appear to respond to topiramate treatment differentially. Our findings show an effect of topiramate on the increasing trend of abstinence from methamphetamine, suggesting that a tailored intervention strategy is needed for treating methamphetamine addiction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Gravity dependence of subjective visual vertical variability.

    PubMed

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

    2009-09-01

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

  18. Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson's disease

    PubMed Central

    Morrow, Bret A.; Roth, Robert H.; Redmond, D. Eugene; Elsworth, John D.

    2011-01-01

    Methamphetamine is a CNS stimulant with limited therapeutic indications, but is widely abused. Short-term exposure to higher doses, or long-term exposure to lower doses, of methamphetamine induces lasting damage to nigrostriatal dopamine neurons in man and animals. Strong evidence indicates that the mechanism for this detrimental effect on dopamine neurons involves oxidative stress exerted by reactive oxygen species. This study investigates the relative susceptibility of dopamine neurons in mid-gestation, young, and adult (not aged) monkeys to 4 treatments with methamphetamine over 2 days. Primate dopamine neurons undergo natural cell death at mid-gestation, and we hypothesized that during this event they are particularly vulnerable to oxidative stress. The results indicated that at mid-gestation and in adults, dopamine neurons were susceptible to methamphetamine-induced damage, as indicated by loss of striatal TH immunoreactivity and dopamine concentration. However, dopamine neurons in young animals appeared totally resistant to the treatment, despite this group having higher brain levels of methamphetamine 3 hours after administration than the adults. As a possible explanation for the protection, striatal GDNF levels were elevated in young animals 1-week after treatment, but not in adults following methamphetamine treatment. Implications of these primate studies are: 1) the susceptibility of dopamine neurons at mid-gestation to methamphetamine warns against the risk of exposing pregnant women to the drug or oxidative stressors, and supports the hypothesis of Parkinson's disease being associated with oxidative stress during development, 2) elucidation of the mechanism of resistance of dopamine neurons in the young animals to methamphetamine-induced oxidative stress may provide targets for slowing or preventing age- or disease-related loss of adult nigrostriatal DA neurons, and 3) the increased striatal production of GDNF in young animals, but not in adults, in

  19. 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.

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

    PubMed

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

    2005-12-15

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

  1. White-matter abnormalities in brain during early abstinence from methamphetamine abuse.

    PubMed

    Tobias, Marc C; O'Neill, Joseph; Hudkins, Matthew; Bartzokis, George; Dean, Andrew C; London, Edythe D

    2010-03-01

    Previous studies revealed microstructural abnormalities in prefrontal white matter and corpus callosum of long-term abstinent chronic methamphetamine abusers. In view of the importance of the early abstinence period in treatment retention, we compared 23 methamphetamine-dependent subjects abstinent from methamphetamine for 7-13 days with 18 healthy comparison subjects. As certain metabolic changes in the brain first manifest after early abstinence from methamphetamine, it is also possible that microstructural white-matter abnormalities are not yet present during early abstinence. Using diffusion tensor imaging at 1.5 T, fractional anisotropy (FA) was measured in prefrontal white matter at four inferior-superior levels parallel to the anterior commissure-posterior commissure (AC-PC) plane. We also sampled FA in the corpus callosum at the midline and at eight bilateral, fiber-tract sites in other regions implicated in effects of methamphetamine. The methamphetamine group exhibited lower FA in right prefrontal white matter above the AC-PC plane (11.9% lower; p = 0.007), in midline genu corpus callosum (3.9%; p = 0.019), in left and right midcaudal superior corona radiata (11.0% in both hemispheres, p's = 0.020 and 0.016, respectively), and in right perforant fibers (7.3%; p = 0.025). FA in left midcaudal superior corona radiata was correlated with depressive and generalized psychiatric symptoms within the methamphetamine group. The findings support the idea that methamphetamine abuse produces microstructural abnormalities in white matter underlying and interconnecting prefrontal cortices and hippocampal formation. These effects are already present during the first weeks of abstinence from methamphetamine and are linked to psychiatric symptoms assessed during this period.

  2. 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.

  3. Gene-dose dependent effects of methamphetamine on interval timing in dopamine-transporter knockout mice.

    PubMed

    Meck, Warren H; Cheng, Ruey-Kuang; MacDonald, Christopher J; Gainetdinov, Raul R; Caron, Marc G; Cevik, Münire Özlem

    2012-03-01

    The dopamine transporter (DAT) is the major regulator of the spatial and temporal resolution of dopaminergic neurotransmission in the brain. Hyperdopaminergic mice with DAT gene deletions were evaluated for their ability to perform duration discriminations in the seconds-to-minutes range. DAT -/- mice were unable to demonstrate temporal control of behavior in either fixed-interval or peak-interval timing procedures, whereas DAT +/- mice were similar to DAT +/+ mice under normal conditions. Low to moderate-dose methamphetamine (MAP) challenges indicated that DAT +/- mice were less sensitive to the clock-speed enhancing effects of MAP compared with DAT +/+ mice. In contrast, DAT +/- mice were more vulnerable than DAT +/+ mice to the disruptive effects of MAP at high doses as revealed by the elevation of response rate in the right hand tail of the Gaussian-shaped timing functions. Moreover, this treatment made DAT +/- mice functionally equivalent to DAT -/- mice in terms of the loss of temporal control. Taken together, these results demonstrate the importance of dopaminergic control of interval timing in cortico-striatal circuits and the potential link of timing dysfunctions to schizophrenia and drug abuse. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse.

    PubMed

    Berman, S M; Voytek, B; Mandelkern, M A; Hassid, B D; Isaacson, A; Monterosso, J; Miotto, K; Ling, W; London, E D

    2008-09-01

    Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

  5. Human immunodeficiency virus infection heightens concurrent risk of functional dependence in persons with long-term methamphetamine use.

    PubMed

    Blackstone, Kaitlin; Iudicello, Jennifer E; Morgan, Erin E; Weber, Erica; Moore, David J; Franklin, Donald R; Ellis, Ronald J; Grant, Igor; Woods, Steven Paul

    2013-01-01

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

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

    PubMed

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

    2014-01-01

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

  7. The Impact of Exercise On Depression and Anxiety Symptoms Among Abstinent Methamphetamine-Dependent Individuals in A Residential Treatment Setting.

    PubMed

    Rawson, Richard A; Chudzynski, Joy; Gonzales, Rachel; Mooney, Larissa; Dickerson, Daniel; Ang, Alfonso; Dolezal, Brett; Cooper, Christopher B

    2015-10-01

    This paper reports data from a study designed to determine the impact of an 8-week exercise program on depression and anxiety symptoms among newly abstinent methamphetamine (MA)-dependent individuals in residential treatment. One hundred thirty-five MA-dependent individuals, newly enrolled in residential treatment, were randomly assigned to receive either a 3-times-per-week, 60-minute structured exercise program for 8 weeks (24 sessions) or an equivalent number of health education sessions. Using mixed-modeling repeated-measures regression, we examined changes in weekly total depression and anxiety scores as measured by the Beck Depression Inventory and Beck Anxiety Inventory over the 8-week study period. Mean age of participants was 31.7 (SD = 6.9); 70.4% were male and 48% Latino. Analyses indicate a significant effect of exercise on reducing depression (β = -0.63, P = 0.001) and anxiety (β = -0.95, P=0.001) symptoms (total scores) over the 8-week period compared to a health education control group. A significant dose interaction effect between session attendance and exercise was found as well on reducing depression (β = -0.61, P < 0.001) and anxiety symptoms (β = -0.22, P=0.009) over time compared to the control group. Results support the role of a structured exercise program as an effective intervention for improving symptoms of depression and anxiety associated with MA abstinence. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

    PubMed

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

    2010-12-01

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

  10. Does effect from developmental methamphetamine exposure on spatial learning and memory depend on stage of neuroontogeny?

    PubMed

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

    2016-12-22

    Psychostimulants, including methamphetamine (MA), have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed to examine cognitive changes after prenatal and neonatal MA treatment in combination with chronic MA exposure in adulthood of male rats. Eight groups of male rats were tested in adulthood: males whose mothers were exposed to MA (5 mg/kg) or saline (SA, 1 ml/kg) during the first half of gestation period (GD 1-11), the second half of gestation period (GD 12-22) and neonatal period (PD 1-11). In addition, we compared indirect neonatal application via the breast milk with the group of rat pups that received MA or SA directly by injection (PD 1-11). Males were tested in adulthood for cognitive changes in the Morris Water Maze (MWM). MWM experiment lasted for 12 days: Learning (Day 1-6), Probe test (Day 8) and Retrieval Memory test (Day 12). Each day of the MWM animals were injected with MA (1 mg/kg) or SA (1 ml/kg). Prenatal MA exposure did not induce changes in learning abilities of male rats, but neonatal exposure to MA leads to an increase search errors and latencies to find the hidden platform. Prenatal and also neonatal MA exposure impaired cognitive ability to remember the position of the platform in Retrieval Memory test in adulthood. Animals exposed to the prenatal treatment within the second half of gestation (ED 12-22) swam longer, slower and spent more time to find the hidden platform in Retrieval Memory test than animals exposed throughout other periods. The present study demonstrated that stage of development is crucial for determination the cognitive deficits induced by prenatal or neonatal MA exposure.

  11. Enzyme immunoassay for methamphetamine.

    PubMed

    Aoki, K; Kuroiwa, Y

    1983-01-01

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

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

    PubMed

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

    2010-04-01

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

  13. [Clinical characteristics of dappou herb use--disorder patients at the drug dependence clinic: a comparison with methamphetamine use-disorder patients].

    PubMed

    Tanibuchi, Yuko; Matsumoto, Toshihiko; Kobayashi, Ohji; Wada, Kiyoshi

    2013-01-01

    Use of the so-called "dappou herb," a street drug typically produced by mixing herbs with synthetic cannabinoid (estimated to be the pharmacologically effective ingredient), has recently spread to young people in Japan who consider it a new recreational drug. It is not legally regulated because no illicit ingredients have been detected in the drug by conventional screening tests. It is easily obtained via the Internet or from street vendors. As the population abusing this drug has grown, medical problems such as psychosis, disturbances of consciousness caused by acute intoxication, and social problems such as traffic accidents while under the influence of the drug have been increasingly reported. However, few psychiatric symptoms associated with it have been identified, and little is known about the psychosocial features of abusers. The purpose of the present study was to examine the clinical and psychosocial features of outpatients with dappou herb use disorder. Subjects were 15 male outpatients with dappou herb use disorder who had their first medical examination at the Drug Dependence Clinic in the Center Hospital, National Center of Neurology and Psychiatry between November 2009 and April 2012. The control group comprised 28 age-matched oupatients who had methamphetamine use disorder, the most serious drug-related problem in Japan since the 1950s. They underwent their first medical examination at the same clinic during the same time frame as the study subjects. Clinical and psychosocial information on subjects and controls including life histories (educational, occupational, and criminal) and clinical information (history of psychoactive substance use, access to the mainly abused drug, and DSM-IV diagnoses of substance use disorder and comorbid psychiatric disorders) were collected from medical records. These variables were compared between the two groups. Analyses revealed differences in the life history and clinical characteristics between the subjects and

  14. Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure.

    PubMed

    Gonzalez, Raul; Rippeth, Julie D; Carey, Catherine L; Heaton, Robert K; Moore, David J; Schweinsburg, Brian C; Cherner, Mariana; Grant, Igor

    2004-11-11

    Abuse of the stimulant drug methamphetamine is associated with neural injury and neuropsychological (NP) deficits, while the residual effects of marijuana use remain uncertain. We sought to determine if methamphetamine dependent persons who also met criteria for marijuana abuse or dependence evidenced different NP performance than those with dependence for methamphetamine alone. We examined three groups that did not differ significantly on important demographic factors: (1) subjects with a history of methamphetamine dependence and history of marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a control group with minimal or no drug use (n=41). A comprehensive NP battery was administered and performance was quantified for five cognitive ability areas. The METH+/MJ- group generally demonstrated the greatest NP impairment, with statistically significant differences observed between the METH+/MJ- and control group in learning, retention/retrieval, and a summary score of global NP performance. The METH+/MJ+ group did not differ significantly from the control or METH+/MJ- group on any NP ability. However, there was a significant linear trend in the global NP score suggesting that the METH+/MJ+ performed intermediate to the control and METH+/MJ- groups. Based on these findings, we cannot conclude that there is a protective effect of marijuana use in methamphetamine users; however, marijuana use clearly did not appear to exacerbate methamphetamine neurotoxicity. Further investigations are needed to determine if the emerging literature, suggesting that certain cannabinoids might have neuroprotective actions, is generalizable to community-dwelling substance abusers.

  15. Mind Over Matter: Methamphetamine

    MedlinePlus

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

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

    PubMed

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

    2017-03-01

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

  17. Short-term, low-dose varenicline administration enhances information processing speed in methamphetamine-dependent users.

    PubMed

    Kalechstein, Ari D; Mahoney, James J; Verrico, Christopher D; De La Garza, Richard

    2014-10-01

    Long-term, high-dose methamphetamine (METH) use is associated with decrements in neurocognition and, given the association between impaired neurocognition and poorer treatment outcomes in individuals dependent on alcohol and drugs, it is considered to be a neglected area of critical concern. The objective of this study was to determine whether varenicline, a partial agonist at α4β2- and a full agonist at α7-nicotinic acetylcholine receptors, enhances attention/information processing speed, episodic memory, and working memory in non-treatment seeking METH-dependent participants. Twenty-six participants were randomly assigned to receive oral placebo or oral varenicline (titrated up to 1 mg) over 5 days during three separate inpatient phases, and 17 completed each inpatient phase. Participants were predominately male (71%) and Caucasian (71%). Varenicline significantly improved reaction time on the n-back for visual stimuli (F(1,47)=5.369, p=0.025, η2=0.103), and a trend was observed for improvement in reaction time for auditory stimuli (F(1,47)=3.141, p=0.083, η2=0.063). For those study participants whose reaction time was in the lower half of the distribution at baseline, the effect was even more pronounced for auditory (F(1,22)=5.287, p=0.031, η2=0.194) and visual (F(1,22)=11.981, p=0.002, η2=0.353) stimuli relative to placebo. In contrast, varenicline did not modulate mean or maximum span of working memory or performance on tests of episodic memory or attention (p's>0.05). Given the potential importance of this finding, it should be replicated in a larger sample over a longer treatment period with a higher dose of varenicline (2 mg). clinicalTrials.gov Identifier NCT01571167. Copyright © 2014. Published by Elsevier Ltd.

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

    PubMed Central

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

    2015-01-01

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

  19. 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

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

    PubMed

    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

    2012-07-01

      Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled out-patient trial tested topiramate for treating methamphetamine addiction.   Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 25 mg/day [DOSAGE ERROR CORRECTED] 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.   The trial was conducted at eight medical centers in the United States.   One hundred and forty methamphetamine-dependent adults took part in the trial.   The primary outcome was abstinence from methamphetamine during weeks 6-12. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables.   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.   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. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  1. Methamphetamine (Meth)

    MedlinePlus

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

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

    PubMed

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

    2003-03-01

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

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

    PubMed

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

    2008-05-30

    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]. 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. 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.

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

    PubMed

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

    1988-01-01

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

  5. 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

  6. 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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2013-01-01

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

  10. 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

  11. 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

  12. 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.

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

    PubMed

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

    2004-06-28

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

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

    PubMed

    Nonnemaker, James; Engelen, Mark; Shive, Daniel

    2011-05-01

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

  15. Glial dysfunction in abstinent methamphetamine abusers.

    PubMed

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

    2010-05-01

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

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

    PubMed

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

    2016-12-01

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

  17. Profiles associated with treatment retention in Japanese patients with methamphetamine use disorder: preliminary survey.

    PubMed

    Kobayashi, Ohji; Matsumoto, Toshihiko; Otsuki, Masaki; Endo, Keiko; Okudaira, Kenichi; Wada, Kiyoshi; Hirayasu, Yoshio

    2008-10-01

    To identify profiles associated with treatment retention in Japanese patients with methamphetamine use disorder. The study used a retrospective design based on clinical records. The subjects were 101 patients at the Kanagawa Psychiatric Center, Serigaya Hospital, who were diagnosed as having methamphetamine use disorder. They were divided in two groups, namely those who remained in treatment 3 months after the initial assessment, and those who did not. The primary analysis compared patient profiles between the two groups to detect discriminating variables, which were then submitted for secondary analysis using logistic regression to determine the most relevant predictor of retention. Primary analysis indicated that older age, having psychotic symptoms, receiving public assistance, and history of incarceration were associated with treatment retention after 3 months. Secondary analysis showed that positive history of incarceration was the most significant predictor of the outcome. History of incarceration had the most significant treatment-retention effect on Japanese patients with methamphetamine use disorder. The development and introduction of integrated programs that link methamphetamine-dependent offenders to drug treatment is recommended in outpatient treatment for Japanese patients with methamphetamine user disorder.

  18. Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review.

    PubMed

    Nordahl, Thomas E; Salo, Ruth; Leamon, Martin

    2003-01-01

    Methamphetamine use is on the rise, with an imminent upsurge of abuse and dependence reported across the United States. Currently, preliminary evidence suggests that methamphetamine dependence may cause long-term neural damage in humans, with concomitant deleterious effects on cognitive processes such as memory and attention. This selective review provides an outline and synthesis of studies that assess the neurotoxic mechanisms of methamphetamine, as well as those that evaluate the cognitive sequelae of methamphetamine abuse.

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

    PubMed

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

    2012-12-01

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

  20. Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes.

    PubMed

    Nohesara, Shabnam; Ghadirivasfi, Mohammad; Barati, Mahmood; Ghasemzadeh, Mohammad-Reza; Narimani, Samira; Mousavi-Behbahani, Zohreh; Joghataei, Mohammadtaghi; Soleimani, Mansoureh; Taban, Mozhgan; Mehrabi, Soraya; Thiagalingam, Sam; Abdolmaleky, Hamid Mostafavi

    2016-12-01

    Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively. We found statistically significant DNA hypomethylation of the promoter regions of DRD3 (P = 0.032), DRD4 (P = 0.05), MB-COMT (P = 0.009), and AKT1 (P = 0.0008) associated with increased expression of the corresponding genes in patients with methamphetamine psychosis (P = 0.022, P = 0.034, P = 0.035, P = 0.038, respectively), and to a lesser degree in some of the candidate genes in non-psychotic patients versus the control subjects. In general, methamphetamine dependency is associated with reduced DNA methylation and corresponding increase in expression of several key genes involved in the pathogenesis of psychotic disorders. While these epigenetic changes can be useful diagnostic biomarkers for psychosis in methamphetamine abusers, it is also consistent with the use of methyl rich diet for prevention or suppression of psychosis in these patients. However, this needs to be confirmed in future studies. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    Kinner, Stuart A; Degenhardt, Louisa

    2008-05-01

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

  2. Effects of methamphetamine on duration discrimination.

    PubMed

    Cevik, Münire Ozlem

    2003-08-01

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

  3. 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…

  4. 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…

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    1997-01-01

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

  8. Methamphetamine Use and Pulmonary Hypertension

    MedlinePlus

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

  9. The sigma receptor agonist SA4503 both attenuates and enhances the effects of methamphetamine

    PubMed Central

    Rodvelt, Kelli R.; Oelrichs, Clark E.; Blount, Lucas R.; Fan, Kuo-Hsien; Lever, Susan Z.; Lever, John R.; Miller, Dennis K.

    2011-01-01

    Background Methamphetamine’s behavioral effects have been attributed to its interaction with monoamine transporters; however, methamphetamine also has affinity for sigma receptors. Method The present study investigated the effect of the sigma receptor agonist SA 4503 and the sigma receptor antagonists BD-1047 and BD-1063 on methamphetamine-evoked [3H] dopamine release from preloaded rat striatal slices. The effect of SA 4503 on methamphetamine-induced hyperactivity and on the discriminative stimulus properties of methamphetamine also was determined. Results SA 4503 attenuated methamphetamine-evoked [3H]dopamine release in a concentration-dependent manner. BD-1047 and BD-1063 did not affect release. SA 4503 dose-dependently potentiated and attenuated methamphetamine-induced hyperactivity. SA 4503 pretreatment augmented the stimulus properties of methamphetamine. Conclusions Our findings indicate that SA 4503 both enhances and inhibits methamphetamine’s effects and that sigma receptors are involved in the neurochemical, locomotor stimulatory and discriminative stimulus properties of methamphetamine. PMID:21277708

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

    PubMed

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

    2009-08-01

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

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

    PubMed

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

    2008-04-28

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

  12. A dysbiotic subpopulation of alcohol-dependent subjects.

    PubMed

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

    2015-01-01

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

  13. A dysbiotic subpopulation of alcohol-dependent subjects

    PubMed Central

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

    2015-01-01

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

  14. The Impact of Age, HIV Serostatus and Seroconversion on Methamphetamine Use

    PubMed Central

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

    2016-01-01

    Background Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. Objectives Study aims were to investigate whether 1) methamphetamine use differs by age and HIV serostatus and 2) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. Methods This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. Results Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (β = −.16, p = .01) and a fewer number of days (β = −.18, p = .004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e., grams per day used) was greater among the younger, relative to the older, HIV+ group (p = .02), and increased for both age groups following seroconversion (p < .001). Conclusion These analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum. PMID:26837461

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

    PubMed

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

    2016-03-01

    Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. Study aims were to investigate whether (i) methamphetamine use differs by age and HIV serostatus, and (ii) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (β = -0.16, p = 0.01) and a fewer number of days (β = -0.18, p = 0.004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e. grams per day used) was greater among the younger, relative to the older, HIV+ group (p = 0.02), and increased for both age groups following seroconversion (p < 0.001). These analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum.

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

    PubMed

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

    2013-01-01

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

  17. Alternative Reinforcer Response Cost Impacts Methamphetamine Choice in Humans

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-01

    Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Influence of Aripiprazole Pretreatment on the Reinforcing Effects of Methamphetamine In Humans

    PubMed Central

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

    2013-01-01

    Methamphetamine use disorders remain a significant public health concern. Methamphetamine produces its behavioral effects by facilitating release of monoamines like dopamine (DA) and serotonin (5-HT). Results from animal studies show that acute pretreatment with DA and 5-HT antagonists attenuates the effects of methamphetamine, but this area remains largely unexplored in humans. This study sought to assess whether aripiprazole, a partial agonist at D2/5-HT1A receptors and an antagonist at 5-HT2A receptors, would attenuate the reinforcing and subject-rated effects of oral methamphetamine. Seven subjects with histories of recreational stimulant use completed a placebo-controlled, crossover, double-blind protocol in which they first sampled doses of oral methamphetamine (0, 4, 8 or 16 mg) following acute pretreatment with aripiprazole (0 and 15 mg). During each Sampling Session, subjects also completed a battery of subject-rated, cardiovascular, and other performance measures. In subsequent Self-Administration Sessions, subjects were provided the opportunity to earn the previously sampled methamphetamine dose on a progressive-ratio procedure. Methamphetamine functioned as a reinforcer, produced prototypical stimulant-like subject-rated and cardiovascular effects (e.g., increased ratings of Stimulated; elevated blood pressure). Aripiprazole reduced methamphetamine self-administration and attenuated some of the positive subject-rated effects of methamphetamine (e.g., ratings of Like Drug). These results indicate that acute aripiprazole pretreatment attenuates the abuse-related effects of methamphetamine. PMID:23994622

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

    PubMed

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

    2013-12-02

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

  2. Methamphetamine abuse and dentistry.

    PubMed

    Hamamoto, D T; Rhodus, N L

    2009-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2016-11-15

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

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

    PubMed

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

    2008-01-01

    Methamphetamine dependence is an emerging epidemic confronting physicians. In an effort to improve understanding of its impact, the authors presented an educational workshop at a national meeting for general internists featuring small group discussions with patients in recovery (PIR) from methamphetamine dependence. Participants rated the workshop highly, stating it would lead to concrete change in their teaching, research, or patient care practices and they would invite the workshop to their institution for presentation. Direct interaction with PIR was the most valued aspect of the workshop. Lessons learned included patient's fear of being "turned in" limits disclosure of methamphetamine use to physicians; active users have little insight into methamphetamine-related changes in physical appearance; and a sense of productivity reinforces ongoing methamphetamine use. Workshops that include small group discussions between physicians and PIR are an innovative, practical, and acceptable method to teach physicians about their role in helping patients with substance dependence.

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

    PubMed

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

    2012-12-01

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

  8. 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

  9. 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

  10. The dependence of the incorporation of methamphetamine into rat hair on dose, frequency of administration and hair pigmentation.

    PubMed

    Han, Eunyoung; Park, Yonghoon; Kim, Eunmi; Lee, Sooyeun; Choi, Hwakyung; Chung, Heesun; Song, Joon Myong

    2010-10-15

    In this paper, the incorporation of methamphetamine (MA) into rat hair was studied. The main purpose of this study was to investigate whether MA can be detected or positive hair results can be obtained in hair of rats administered a single dose of MA. The relationship between dose and frequency of administration and the concentrations of MA and its metabolite, amphetamine (AP), in rat hair were evaluated and the MA and AP concentrations in white and pigmented hair were compared. MA was administered to rats as follows: low dose (0.5mg/kg/day), medium dose (2mg/kg/day) and high dose (10mg/kg/day). The frequency of administration was one time per day for 1, 2, 3, 4, 5, 15 and 30 days. Hair and urine samples were collected from rats and analyzed by gas chromatography/mass spectrometry (GC/MS). MA could be identified in pigmented rat hair when MA was administered for 4 or more days at low daily dose and on day 1 following administration of medium and high daily doses. Positive results for MA were obtained from pigmented rat hair when MA was administered for 30 days at low daily dose, for 4 or more days at medium daily dose, or for 2 or more days at high daily dose. The concentrations of MA and AP found in rat hair were proportional to the dose and frequency of administration. The concentrations of MA and AP in pigmented rat hair were 2-10 times higher than those in white rat hair. The results of this study on the incorporation of MA into rat hair can serve as a model to better understand the incorporation of MA into human hair even though there are differences between animal models and human hair. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. 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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Bupropion for the treatment of methamphetamine dependence in non-daily users: a randomized, double-blind, placebo-controlled trial.

    PubMed

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

    2015-05-01

    Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users. 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-min, 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). 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 to 12) was achieved by 47% of participants taking bupropion. 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. Published by Elsevier Ireland Ltd.

  16. Feasibility and acceptability of a phase II randomized pharmacologic intervention for methamphetamine dependence in high-risk men who have sex with men

    PubMed Central

    Das, Moupali; Santos, Deirdre; Matheson, Tim; Santos, Glenn-Milo; Chu, Priscilla; Vittinghoff, Eric; Shoptaw, Steve; Colfax, Grant N.

    2010-01-01

    Objective To determine whether actively using, methamphetamine (meth)-dependent men who have sex with men (MSM) could be enrolled and retained in a pharmacologic intervention trial, and the degree to which participants would adhere to study procedures, including medication adherence. Study design Phase II randomized, double-blind trial of bupropion vs. placebo. Methods Thirty meth-dependent, sexually active MSM were randomized to receive daily bupropion XL 300 mg or placebo for 12 weeks. Participants received weekly substance use counseling, provided weekly urine specimens, and completed monthly audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps (the number of distinct MEMS cap openings divided by the number of expected doses) and self-report. Results Ninety percent completed the trial: 89% of monthly ACASIs were completed, 81% of study visits were attended, and 81% of urine samples were collected. Adherence by MEMS cap was 60% and by self-report was 81% and did not differ significantly by treatment assignment. The median number of positive urine samples was 5.5 out of a possible 11 (50%). Participants in both arms reported similar declines in the median number of sex partners (P = 0.52). No serious adverse events occurred and there were no significant differences in adverse events by treatment assignment (P = 0.11). Conclusions It is feasible to enroll and retain actively using, meth-dependent MSM in a pharmacologic intervention. Bupropion was well tolerated. Study participation and retention rates were high, however, study drug medication adherence was only moderate. Findings support a larger trial with improved adherence support to evaluate the efficacy of bupropion and other pharmacologic interventions for meth dependence in this population. PMID:20397286

  17. Long-lasting change in brain dynamics induced by methamphetamine: enhancement of protein kinase C-dependent astrocytic response and behavioral sensitization.

    PubMed

    Narita, Minoru; Miyatake, Mayumi; Shibasaki, Masahiro; Tsuda, Makoto; Koizumi, Schuichi; Narita, Michiko; Yajima, Yoshinori; Inoue, Kazuhide; Suzuki, Tsutomu

    2005-06-01

    It is well known that long-term exposure to psychostimulants induces neuronal plasticity. Recently, accumulating evidence suggests that astrocytes may actively participate in synaptic plasticity. In this study, we found that in vitro treatment of cortical neuron/glia co-cultures with either methamphetamine (METH) or morphine (MRP) caused the activation of astrocytes via protein kinase C (PKC). Purified astrocytes were markedly activated by METH, whereas MRP had no such effect. METH, but not MRP, caused a long-lasting astrocytic activation in cortical neuron/glia co-cultures. Furthermore, MRP-induced behavioral sensitization to hyper-locomotion was reversed by 2 months of withdrawal following intermitted MRP administration, whereas behavioral sensitization to METH-induced hyper-locomotion was maintained even after 2 months of withdrawal. Consistent with this cell culture study, in vivo treatment with METH, which was associated with behavioral sensitization, caused a PKC-dependent astrocytic activation in the cingulate cortex and nucleus accumbens of mice. These findings provide direct evidence that METH induces a long-lasting astrocytic activation and behavioral sensitization through the stimulation of PKC in the rodent brain. In contrast, MRP produced a reversible activation of astrocytes via neuronal PKC and a reversibility of behavioral sensitization. This information can break through the definition of drugs of abuse and the misleading of concept that morphine produces a long-lasting neurotoxicity.

  18. 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

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

    PubMed

    Shen, H; Mohammad, A; Ramroop, J; Smith, S S

    2013-12-19

    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 (24h) following chronic exposure (3mg/kg, i.p. for 3-5weeks) 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 (three-fold) hippocampal expression of α4βδ GABAA receptors (GABARs) during METH withdrawal (24h-4weeks) 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 (30nM) increased neuronal excitability, assessed with current clamp and cell-attached recordings in CA1hippocampus, one CNS site which regulates anxiety. α4βδ GABARs were first increased 1h after METH exposure and recovered 6weeks after METH withdrawal. Similar increases in α4βδ GABARs and anxiogenic effects of 3α,5β-THP were noted in rats during METH withdrawal (24h). 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 (10mg/kg, i.p., 3×) reduced α4βδ expression and prevented the anxiogenic effect of 3α,5β-THP after METH withdrawal. Our findings suggest a novel

  20. 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.

  1. Alcohol-Dependent Subjects Show Different Personality Traits Compared With Subjects With Multiple Substance Dependence: Preliminary Data.

    PubMed

    Koller, Gabi; Preuss, Ullrich; Lü, Osman; Soyka, Michael; Pogarell, Oliver

    2015-01-01

    We compared personality traits of 27 persons with multiple substance dependence with personality data of 52 alcohol-dependent persons regarding their personality traits and disorders (obtained by using SCID-II, TCI and NEO FFI). Both patient groups were free of any other mental disorder. In SKD-II, we found significant differences in the male group in dependent and scizotypic personality disorder. There were no significant differences in the female group, but sample was very small. We also found significant differences between alcohol-dependent and multiple substance-dependent persons in extraversion and novelty seeking. We detected significant differences in personality disorders evaluated by SCID-II. Temperament and character items—as evaluated by NEO FFI and TCI—showed also significant differences in personality traits. Given the limited number of subjects, the data should be regarded as preliminary until replicated in a larger sample. Nevertheless, the findings may be of clinical relevance with respect to prognosis or individualized treatment. These findings should be treated with caution until replicated.

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

    PubMed

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

    2009-03-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2003-02-14

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

  6. Methamphetamine-Associated Cardiomyopathy

    PubMed Central

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

    2015-01-01

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

  7. Neurotoxic effects of methamphetamine.

    PubMed

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

    2010-01-01

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

  8. Glutamatergic neurotransmission and protein kinase C play a role in neuron-glia communication during the development of methamphetamine-induced psychological dependence.

    PubMed

    Miyatake, Mayumi; Narita, Minoru; Shibasaki, Masahiro; Nakamura, Atsushi; Suzuki, Tsutomu

    2005-09-01

    Methamphetamine (METH) is a strongly addictive psychostimulant that dramatically affects the central nervous system (CNS). On the other hand, protein kinase C (PKC) plays a major role in cellular regulatory and signalling processes that involve protein phosphorylation. The purpose of this study was to investigate the role of neuronal and astrocytic PKC in changes in the central glutamatergic system induced by METH. We show here that in vitro treatment with METH caused the phosphorylation of both neuronal and astrocytic PKC and the activation of astrocytes in cortical neuron/glia co-cultures. Treatment of cortical neuron/glia co-cultures with either the PKC activator phorbol 12,13-dibutyrate (PDBu) or glutamate also caused the PKC-dependent activation of astrocytes. The PKC inhibitor chelerythrine suppressed the Ca2+ responses to glutamate in both cortical neurons and astrocytes. Moreover, a low concentration of PDBu significantly enhanced the Ca2+ responses to glutamate, but not to dopamine, in both cortical neurons and astrocytes. Notably, treatment with METH also enhanced the Ca2+ responses to glutamate in cortical neurons. The activation of astrocytes induced by METH was also reversed by co-treatment with glutamate receptor antagonists (ifenprodil, DNQX or MPEP) in cortical neuron/glia co-cultures. In the conditioned place preference paradigm, intracerebroventricular administration of glutamate receptor antagonists (ifenprodil, DNQX or MPEP) attenuated the METH-induced rewarding effect. These findings provide evidence that the changes in PKC-dependent neuronal and astrocytic glutamatergic transmission induced by METH may, at least in part, contribute to the development of psychological dependence on METH.

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

    PubMed

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

    2011-08-01

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

  10. The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse.

    PubMed

    Shepard, Jack D; Bossert, Jennifer M; Liu, Shirley Y; Shaham, Yavin

    2004-06-01

    Brain noradrenaline is involved in footshock stress-induced reinstatement of drug seeking in a rat relapse model. We studied whether yohimbine, an alpha-2 adrenoceptor antagonist that increases noradrenaline release and induces anxiety-like responses in human and nonhuman subjects, would reinstate methamphetamine seeking in rats. In experiment 1, the effect of yohimbine (1.25-2.5 mg/kg) on reinstatement was compared with that of intermittent footshock (5 min;.2-.6 mA) in rats that were trained to lever press for intravenous methamphetamine (9-11 days) and subsequently underwent 7 days of extinction training. In experiment 2, the effect of yohimbine on reinstatement of drug seeking was determined during early (1 day) and late (21 or 51 days) withdrawal periods. On the test days, rats were first given 3-hour extinction sessions and were then tested for reinstatement induced by yohimbine. In experiment 1, both yohimbine and footshock stress reinstated methamphetamine seeking after extinction. In experiment 2, extinction responding was higher after 21 or 51 withdrawal days than after 1 withdrawal day. In contrast, no significant time-dependent changes in yohimbine-induced reinstatement were observed. Results indicate that yohimbine is a potent stimulus for reinstatement of methamphetamine seeking in a rat relapse model.

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

    PubMed

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

    2012-09-01

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

  12. Feasibility, acceptability and tolerability of targeted naltrexone for non-dependent methamphetamine-using and binge-drinking men who have sex with men

    PubMed Central

    Santos, Glenn-Milo; Coffin, Phillip; Santos, Deirdre; Huffaker, Shannon; Matheson, Tim; Euren, Jason; DeMartini, Anna; Rowe, Christopher; Hahn, Judith A.; Vlahov, David; Vittinghoff, Eric; Batki, Steven L.

    2015-01-01

    Background There are no effective pharmacologic strategies for non-dependent methamphetamine (meth)-using and binge-drinking MSM at high-risk for HIV. We sought to determine the feasibility of enrolling and retaining this population in a pharmacologic trial; the acceptability of pharmacotherapy study procedures; and the tolerability of targeted naltrexone versus placebo. Methods Thirty meth-using and binge-drinking MSM were randomly assigned 1:1 to 50mg naltrexone or placebo for 8 weeks for targeted administration (i.e., during craving or in anticipation of meth or alcohol use). Substance use counseling and behavioral assessments were conducted every two weeks. Medication use was measured using WisePill dispensers. Results Trial completion was 93%; visit completion rate was 95%. Mean weekly number of medication pills taken was 2.2 and was similar between arms. Participant satisfaction rate was 96%. There were no serious adverse events nor differences in adverse event rates between arms. In exploratory intention-to-treat analyses, there were no differences in meth use and drinking. Naltrexone participants had greater reductions in serodiscordant receptive anal intercourse (IRR=0.15; 95%CI=0.05-0.42) and serodiscordant condomless receptive anal intercourse (IRR=0.11; 95%CI=0.03-0.37), compared to placebo. In subgroup analyses among frequent meth-users, naltrexone participants had greater reductions in meth-using days (IRR=0.78; 95%CI=0.62-0.99). In as-treated analyses, frequent study medication users in the naltrexone arm had greater reductions in binge drinking days (IRR=0.72; 95%CI=0.54-0.97). Conclusions Targeted naltrexone is a feasible, acceptable and tolerable intervention strategy for non-dependent meth-using and binge-drinking MSM. Naltrexone was associated with significant sexual risk reductions; and for some individuals, naltrexone was associated with meth and binge-drinking reductions. PMID:26674372

  13. 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…

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

    PubMed

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

    2003-09-30

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

  16. An association between BDNF Val66Met polymorphism and impulsivity in methamphetamine abusers.

    PubMed

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

    2014-10-17

    Recent studies showed an association between a functional polymorphism of BDNF gene (Val66Met) and the susceptibility to methamphetamine addiction. We hypothesized that this polymorphism was associated with methamphetamine abuse and impulsivity in methamphetamine-abuse patients. The polymorphism was genotyped in 200 methamphetamine-abuse patients and 219 healthy controls. The association of the Val66Met polymorphism of the BDNF gene and impulsivity in 138 methamphetamine abusers were assessed using Barratt Impulsivity Scale-11(BIS-11) Chinese version. The relationship between the polymorphism and age of onset of methamphetamine abuse was also examined. Our results showed no significant differences in genotype and allele distributions between the methamphetamine abusers and controls. Within the methamphetamine-abuse group, subjects carried the Met allele had significantly higher attentional impulsivity scores of BIS compared to those with the Val/Val genotype. The Met allele was also associated with earlier age onset of methamphetamine use. Our findings suggest that the BDNF Val66Met gene polymorphism may influence attentional impulsivity in methamphetamine abusers. Moreover, the BDNF Val66Met gene polymorphism may contribute to onset age of methamphetamine use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. 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

  18. Methamphetamine Use in Club Subcultures

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-07-04

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

  20. Research Reports: Methamphetamine

    MedlinePlus

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

  1. Methamphetamine detection in maternal and neonatal hair: implications for fetal safety

    PubMed Central

    Garcia‐Bournissen, F; Rokach, B; Karaskov, T; Koren, G

    2007-01-01

    Background Methamphetamine misuse is a serious health problem of epidemic proportions. Use of this drug, particularly during pregnancy, is difficult to ascertain. Sparse information is available on gestational exposure. Objectives To quantify methamphetamine accumulation in hair, identify the use of methamphetamine with other drugs of abuse and characterise correlations between concentrations of methamphetamine in maternal and neonatal hair. Subjects and methods Motherisk laboratory at the Hospital for Sick Children routinely carries out analysis of methamphetamine in hair. Mothers and infants with positive results for methamphetamine in hair were identified. Drugs present in hair were analysed by ELISA and positive results were confirmed by gas chromatgraphy/mass spectrometry. Results 396 people positive for methamphetamine in their hair were identified from our database. Almost 85% of them were positive for at least one other drug of abuse, mostly cocaine. Eleven mother–baby pairs with hair positive for methamphetamine were identified. Methamphetamine levels in hair ranged between 0.13 and 51.97 ng/mg in the mothers and between 0 and 22.73 ng/mg in the neonates. Methamphetamine levels in mothers and neonates correlated significantly. One (9%) neonate was negative for methamphetamine even though the mother was positive. Conclusion To our knowledge, this is the first report on fetal exposure to methamphetamine during pregnancy, showing transplacental transfer of the drug, with accumulation in fetal hair. Hair measurement for methamphetamine in neonates is a useful screening method to detect intra‐uterine exposure to the drug. The data also indicate that positive exposure to methamphetamine strongly suggests that the person is a polydrug user, which may have important implications for fetal safety. PMID:17077112

  2. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

  3. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-02-01

    Naltrexone and bupropion, when administered alone in clinical trials, modestly reduce amphetamine use. Whether combining these drugs would result in greater reductions in methamphetamine taking relative to either drug alone is undetermined. This study examined the influence of naltrexone, bupropion and a naltrexone-bupropion combination on methamphetamine self-administration in humans. Seven subjects reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind study in which the reinforcing, subject-rated and physiological effects of intranasal methamphetamine (0, 10 and 30 mg) were assessed during maintenance on placebo, naltrexone (50 mg), bupropion (300 mg/day), and naltrexone combined with bupropion. Methamphetamine maintained responding and produced prototypic subjective and physiological effects (e.g., increased ratings of good effects, elevated systolic blood pressure). Maintenance doses were well tolerated and generally devoid of effects. No maintenance condition reduced methamphetamine self-administration or systematically altered the subject-rated effects of methamphetamine. These outcomes demonstrate the robust behavioral effects of methamphetamine that could make it resistant to pharmacological manipulation. Although these outcomes indicate that this combination may be ineffective for managing methamphetamine use disorder, future work should evaluate longer maintenance dosing, individuals with different levels of amphetamine use, adding this combination to a behavioral platform and other pharmacotherapy combinations for reducing methamphetamine use. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2007-09-01

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

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

    PubMed

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

    2011-11-01

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

  8. Neurobehavioral Effects from Developmental Methamphetamine Exposure.

    PubMed

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

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

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

    PubMed

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

    2004-01-01

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

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

    PubMed

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

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. Copyright © 2016 the American Physiological Society.

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

    PubMed

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

    2012-01-01

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

  12. 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

  13. Subjective experience of difficulty depends on multiple cues

    PubMed Central

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

    2017-01-01

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

  14. Boundary Conditions of Methamphetamine Craving

    PubMed Central

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

    2015-01-01

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

  15. 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.…

  16. 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.…

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

    PubMed

    Joubert, L; Harris, W F

    1997-06-01

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

  18. Powerful Behavioral Interactions Between Methamphetamine and Morphine

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-06-21

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

  20. Methamphetamine enhances the cleavage of the cytoskeletal protein tau in the rat brain.

    PubMed

    Wallace, T L; Vorhees, C V; Zemlan, F P; Gudelsky, G A

    2003-01-01

    The view that methamphetamine is neurotoxic to dopaminergic and serotonergic axon terminals has been based largely on biochemical and histological studies. In the present study, methamphetamine-induced structural damage to axons was quantified using a sensitive sandwich enzyme-linked immunosorbent assay developed for the detection of the cleaved form of the cytoskeletal protein tau. The administration of a monoamine-depleting regimen of methamphetamine (4 x 10 mg/kg, i.p. every 2 hours for a total of four injections) produced a time-dependent increase in the concentration of cleaved tau in the striatum. Maximal concentrations of cleaved tau were detected 3 days following methamphetamine administration. Cleaved tau concentrations also were significantly elevated in the dorsal hippocampus and, to a lesser extent, in the prefrontal cortex of methamphetamine-treated rats. Maintenance of rats in a cold (4 degrees C) environment not only prevented the methamphetamine-induced depletion of striatal dopamine and serotonin but also prevented the methamphetamine-induced increase in striatal cleaved tau concentrations. The novel findings from this study are supportive of the view that methamphetamine produces acute structural damage to neurons that may lead to the long-term neurotoxic effects of repeated, high-dose administration of the drug and that cleaved tau reliably quantifies the time-dependent neurotoxic effects of methamphetamine.

  1. Methamphetamine self-administration in humans during D-amphetamine maintenance.

    PubMed

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

    2014-12-01

    Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of D-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that D-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested 2 D-amphetamine maintenance conditions in counterbalanced order (0 and 40 mg/d). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled 1 of 4 doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive-ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 12 items of the drug-effects questionnaires, 8 of which were attenuated by D-amphetamine maintenance (eg, increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by D-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during D-amphetamine maintenance and no adverse events occurred. Although D-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that D-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. High urinary excretion of adrenaline in insulin dependent diabetic subjects.

    PubMed

    Del Rio, G; Marrama, P; Della Casa, L

    1992-01-01

    In view of the hyperglycemic and ketogenic actions of catecholamines, studies on the adrenergic pattern in diabetic patients are relevant to the management of diabetes. We have studied urinary adrenaline and noradrenaline excretion in 4-hour collections in 16 type I diabetic male patients without signs of autonomic or peripheral neuropathy and 11 age-weight matched controls. In diabetic patients adrenaline levels were higher than control subjects (26.8 +/- 3.9 vs 10.7 +/- 3.0 nmol/4h; p < 0.003) but did not differ in respect of noradrenaline (62.6 +/- 6.8 vs 59.6 +/- 10.8 nmol/4h) and creatinine excretion. This finding demonstrates a hyperactivity of the adrenal medulla in diabetic patients without concomitant elevations of noradrenaline. This occurred in absence of hypoglycemia and seems to be a common feature of type I diabetics without complications. Since these levels of adrenaline are sufficient to stimulate both lypolysis and glycogenolysis a previous characterization of adrenomedullary activity may help to better define insulin demands in diabetic patients.

  6. 5-HT(1A)-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians.

    PubMed

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

    2010-10-29

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

  7. 5-HT1A-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians

    PubMed Central

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

    2010-01-01

    No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 µM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal) than either methamphetamine-naïve planarians tested in water or methamphetamine-exposed planarians tested in methamphetamine. A concentration-related inhibition of withdrawal was observed when methamphetamine-exposed planarians were placed into a solution containing either methamphetamine and 5-HT (0.1 – 100 µM) or methamphetamine and the 5-HT1A receptor agonist 8-Hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) (10, 20 µM). Planarians with prior methamphetamine exposure displayed enhanced withdrawal when tested in a solution of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) (1 µM). Methamphetamine-induced withdrawal was not affected by the 5-HT2B/2C receptor agonist meta-chlorophenylpiperazine (m-CPZ) (0.1 – 20 µM). These results provide pharmacological evidence that serotonin-enhancing drugs inhibit expression of methamphetamine physical dependence in an invertebrate model of withdrawal, possibly through a 5-HT1A-like receptor-dependent mechanism. PMID:20709144

  8. 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

  9. The Effect of Buprenorphine on Methamphetamine Cravings.

    PubMed

    Salehi, Mehrdad; Emadossadat, Alireza; Kheirabadi, Gholam Reza; Maracy, Mohammad Reza; Sharbafchi, Mohammad Reza

    2015-12-01

    Methamphetamine (METH) abuse and dependence present a major global problem. We investigated the efficacy of adding buprenorphine in reducing METH cravings during treatment with the Matrix program. This was a randomized, double-blind, controlled clinical trial of 40 men between the age of 18 and 40 years who were referred to the addiction treatment center at Noor Hospital from December 2012 to September 2013. All of the selected subjects participated in the Matrix program and were randomly assigned into 2 groups and given either buprenorphine or a placebo. A 4-month intervention program with buprenorphine or a placebo was arranged for each group. Demographic variables of the 2 groups, descriptive indices from the cocaine craving questionnaire-brief (CCQ-Brief), the ratio of urine tests positive for METH, and the frequency of drug complications were regularly evaluated in both groups every 2 weeks and, if not possible, by the third or fourth week. All analyses were performed by SPSS20 using analysis of covariance, χ, and t tests. The average of indices from the cocaine craving questionnaire-brief score, except the 2 initial measurements, was significantly lower in the intervention group in all measurements (P < 0.05). Apart from weeks 3 and 28, the ratio of positive tests was significantly different in all measurements in both groups (P < 0.05). Buprenorphine augmentation, in comparison with the placebo, significantly reduced the craving to use METH during treatment with the Matrix program.

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

    PubMed Central

    Kim, Airee; Mandyam, Chitra D.

    2014-01-01

    Methamphetamine addicts demonstrate impaired frontal cortical-dependent cognitive function that could result from methamphetamine-induced maladaptive plasticity in the prefrontal cortex. Reduced adult gliogenesis observed in a rodent model of compulsive methamphetamine self-administration could contribute to the maladaptive plasticity in the medial prefrontal cortex (mPFC) as excessive methamphetamine intake is associated with loss of gliogenesis. The present study explored the vulnerability of mPFC progenitors to the duration of various sessions of methamphetamine self-administration in limited and extended access schedule of reinforcement. Proliferation of progenitors via Ki-67 labeling and apoptosis via activated caspase-3 labeling were studied in rats that intravenously self-administered methamphetamine in a limited access (1 h/day: short access (ShA)) or extended access (6 h/day: long access (LgA)) paradigm over 4, 13, 22 or 42 sessions, and in rats that experienced 22 sessions and were withdrawn from self-administration for a period of 4 weeks. Four sessions of LgA methamphetamine enhanced proliferation and apoptosis and forty-two sessions of ShA and LgA methamphetamine reduced proliferation without effecting apoptosis. Withdrawal from twenty-two sessions of methamphetamine enhanced proliferation in LgA animals. Our findings demonstrate that proliferation of mPFC progenitors is vulnerable to psychostimulant exposure and withdrawal with distinct underlying mechanisms relating to methamphetamine toxicity. The susceptibility of mPFC progenitors to even modest doses of methamphetamine could account for the pronounced neuroadaptation in the mPFC linked to methamphetamine abuse. PMID:25260424

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

    PubMed

    Kim, Airee; Mandyam, Chitra D

    2014-11-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2009-02-01

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

  14. Prospective memory impairment in former users of methamphetamine.

    PubMed

    Rendell, Peter G; Mazur, Magdalena; Henry, Julie D

    2009-04-01

    Considerable research indicates that methamphetamine use is associated with neurocognitive impairment, but no empirical study to date has assessed whether these difficulties extend to memory for future intentions (prospective memory). The present study assessed prospective performance on a laboratory measure of prospective memory that closely represents the types of prospective memory tasks that actually occur in everyday life and provides an opportunity to investigate the different sorts of prospective memory failures that occur ("Virtual Week"). Twenty adults with confirmed history of methamphetamine use and dependence, currently engaged in rehabilitation and confirmed to be abstinent for an average period of 6 months, and 20 methamphetamine-naive participants were tested on Virtual Week. Various other aspects of cognitive function were also assessed, including retrospective memory and executive functioning. Methamphetamine users were significantly impaired on Virtual Week, and these deficits did not vary as a function of specific prospective memory task demands. Of all the cognitive measures, cognitive inhibition shared greatest variance with group effects on the prospective memory measure. Prospective memory performance is sensitive to prior methamphetamine use even well into abstinence. Methamphetamine users experience generalized difficulties with prospective memory, suggesting that these deficits are likely to have important implications for day-to-day functioning.

  15. Parental methamphetamine abuse and children.

    PubMed

    McGuinness, Teena M; Pollack, Daniel

    2008-01-01

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

  16. [Impulsive behaviors in opiate-dependent subjects treated with naltrexone].

    PubMed

    Pérez de los Cobos, J; Pinet, C; Ribalta, E; Trujols, J; Casas, M

    1994-01-01

    Thirty three heroin dependents (DSM-III-R) attending a naltrexone clinic were assessed to see if their histories of bulimic and non-suicidal self-aggressive behaviours would allow to predict the therapeutic response of the opioid antagonist. Neither these impulsive behaviours non previous suicide attempts or over-doses could predict such a response, which was evaluated according to the time spent under treatment with naltrexone. Before the administration of naltrexone, one or more of the studied impulsive conducts were detected in 87.8% of the sample (n = 29). None of the patients combined enough criteria to be diagnosed of bulimia (DSM-III-R). In 32 patients the occurrence of changes in the impulsive behaviours studied during the treatment period with the opioid antagonist were determined. These variations were not related to the determinations of abuse drugs in urine or with intake of psychoactive drugs. During the treatment with naltrexone, 15 patients ceased to present self-injuries without suicidal purposes and none of the patients began these behaviours for the first time. However, some patients without a previous history of bulimic behaviour developed this condition during the administration of the opioid antagonist. In this sense, four subgroups of patients can be differentiated according to the moment in which the bulimic behaviour appeared: subgroup A includes 7 individuals (21.7%) who discontinued this behaviour upon receiving the antagonist, while subgroup B (n = 3; 9.3%) is made up of those who presented this behaviour during both heroin consumption and the administration of naltrexone.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2007-04-30

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

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

    PubMed

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

    2014-08-08

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2006-10-01

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

  3. Boundary conditions of methamphetamine craving.

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2012-09-01

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

  6. Patterns of methamphetamine abuse and their consequences.

    PubMed

    Cho, Arthur K; Melega, William P

    2002-01-01

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

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

    PubMed

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

    2010-11-24

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

  8. Methamphetamine and the expanding complications of amphetamines.

    PubMed Central

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

    1999-01-01

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

  9. Methamphetamine-related brainstem haemorrhage.

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2017-06-01

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

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

    PubMed Central

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

    2007-01-01

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

  12. Comparing diet, oral hygiene and caries status of adult methamphetamine users and nonusers: a pilot study.

    PubMed

    Morio, Kimberly A; Marshall, Teresa A; Qian, Fang; Morgan, Teresa A

    2008-02-01

    Methamphetamine users are reported to have marginal dietary habits and high caries rates. The authors compared retrospective dietary patterns, oral hygiene behaviors and current oral health status of methamphetamine users and nonusers in a pilot study. Eighteen adults with a history of methamphetamine use (methamphetamine users) and 18 age- and sex-matched control subjects (nonusers) completed retrospective questionnaires concerning meal patterns, food group intakes, beverage habits, oral hygiene behaviors, smoking behaviors and drug use. The authors performed oral examinations to identify the number of remaining teeth, the number of teeth with obvious decay and presence of visible plaque. Methamphetamine users were more likely to snack without eating defined meals (P = .026), consume regular soda pop (that is, carbonated beverage with sugar) (P = .018), never brush their teeth (P < .001) and smoke (P < .001) than were nonusers. Users had more visible plaque (P < .001), fewer molars (P = .001) and more decay on anterior teeth (P < .001), premolars (P < .001) and molars (P < .001) than did nonusers. The results of this pilot study are consistent with anecdotal reports; methamphetamine users have more gross caries than do nonusers. Marginal dietary and oral hygiene behaviors associated with methamphetamine use likely increase caries risk. Patients at risk or suspected of using methamphetamine require detailed oral hygiene instruction and extensive dietary counseling.

  13. 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. © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Lobelane decreases methamphetamine self-administration in rats.

    PubMed

    Neugebauer, Nichole M; Harrod, Steven B; Stairs, Dustin J; Crooks, Peter A; Dwoskin, Linda P; Bardo, Michael T

    2007-09-24

    Lobelane, a minor alkaloid of Lobelia inflata and a synthetic, des-oxy analog of lobeline, has good affinity for the vesicular monoamine transporter and the dopamine transporter. The current study examined the ability of lobelane to specifically decrease methamphetamine self-administration. Rats were trained on a fixed ratio 5 schedule of reinforcement to self-administer methamphetamine (0.05 mg/kg/infusion, i.v.) or to respond for sucrose pellets. Upon reaching stable responding, rats were pretreated with lobelane (0.1, 1, 3, 5.6, or 10 mg/kg, s.c.) or saline, 15 min prior to the operant session. To assess the effect of repeated lobelane on methamphetamine self-administration, rats were pretreated with lobelane (5.6 or 10 mg/kg, s.c.) for 7 sessions. Behavioral specificity was further investigated by assessing the effects of lobelane (0.1, 1, 3, 5, or 10 mg/kg, s.c.) or saline on locomotor activity. Within the dose range tested, lobelane dose-dependently decreased methamphetamine self-administration, while having no effect on sucrose-maintained responding. Locomotor activity was decreased following only the highest dose of lobelane (10 mg/kg). Across repeated pretreatments, tolerance developed to the effect of lobelane on methamphetamine self-administration, demonstrating that the ability of lobelane to specifically decrease methamphetamine self-administration is a transient effect. Thus, taken together, the results show that although lobelane interacts with the pharmacological targets believed to be responsible for its ability to decrease methamphetamine self-administration, removal of the oxygen functionalities from the lobeline molecule may have afforded a compound with an altered pharmacokinetic and/or pharmacodynamic profile.

  15. Lobelane decreases methamphetamine self-administration in rats

    PubMed Central

    Neugebauer, Nichole M.; Harrod, Steven B.; Stairs, Dustin J.; Crooks, Peter A.; Dwoskin, Linda P.; Bardo, Michael T.

    2007-01-01

    Lobelane, a minor alkaloid of Lobelia inflata and a synthetic, des-oxy analog of lobeline, has good affinity for the vesicular monoamine transporter and the dopamine transporter. The current study examined the ability of lobelane to specifically decrease methamphetamine self-administration. Rats were trained on a fixed ratio 5 schedule of reinforcement to self-administer methamphetamine (0.05 mg/kg/infusion, i.v.) or to respond for sucrose pellets. Upon reaching stable responding, rats were pretreated with lobelane (0.1, 1, 3, 5.6, or 10 mg/kg, s.c.) or saline, 15 min prior to the operant session. To assess the effect of repeated lobelane on methamphetamine self-administration, rats were pretreated with lobelane (5.6 or 10 mg/kg, s.c.) for 7 sessions. Behavioral specificity was further investigated by assessing the effects of lobelane (0.1, 1, 3, 5, or 10 mg/kg, s.c.) or saline on locomotor activity. Within the dose range tested, lobelane dose-dependently decreased methamphetamine self-administration, while having no effect on sucrose-maintained responding. Locomotor activity was decreased following only the highest dose of lobelane (10 mg/kg). Across repeated pretreatments, tolerance developed to the effect of lobelane on methamphetamine self-administration, demonstrating that the ability of lobelane to specifically decrease methamphetamine self-administration is a transient effect. Thus, taken together, the results show that although lobelane interacts with the pharmacological targets believed to be responsible for its ability to decrease methamphetamine self-administration, removal of the oxygen functionalities from the lobeline molecule may have afforded a compound with an altered pharmacokinetic and/or pharmacodynamic profile. PMID:17612524

  16. 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. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

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

    PubMed

    Thom, Katey; Finlayson, Mary; McKenna, Brian

    2011-06-01

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

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

    PubMed

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

    2011-10-01

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

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

    PubMed

    MacLean, Sarah; Harney, Angela; Arabena, Kerry

    2015-01-01

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

  20. Utility of preclinical drug versus food choice procedures to evaluate candidate medications for methamphetamine use disorder.

    PubMed

    Banks, Matthew L

    2017-04-01

    Substance use disorders are diagnosed as a manifestation of inappropriate behavioral allocation toward abused drugs and away from other behaviors maintained by more adaptive nondrug reinforcers (e.g., money and social relationships). Substance use disorder treatment goals include not only decreasing drug-maintained behavior but also promoting behavioral reallocation toward these socially adaptive alternative reinforcers. Preclinical drug self-administration procedures that offer concurrent access to both drug and nondrug reinforcers provide a translationally relevant dependent measure of behavioral allocation that may be useful for candidate medication evaluation. In contrast to other abused drugs, such as heroin or cocaine, preclinical methamphetamine versus food choice procedures have been a more recent development. We hypothesize that preclinical to clinical translatability would be improved by the evaluation of repeated pharmacological treatment effects on methamphetamine self-administration under a methamphetamine versus food choice procedure. In support of this hypothesis, a literature review suggests strong concordance between preclinical pharmacological treatment effects on methamphetamine versus food choice in nonhuman primates and clinical medication treatment effects on methamphetamine self-administration in human laboratory studies or methamphetamine abuse metrics in clinical trials. In conclusion, this literature suggests preclinical methamphetamine versus food choice procedures may be useful in developing innovative pharmacotherapies for methamphetamine use disorder. © 2016 New York Academy of Sciences.

  1. Global patterns of methamphetamine use.

    PubMed

    Chomchai, Chulathida; Chomchai, Summon

    2015-07-01

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

  2. Corpus Callosum Diffusion and Connectivity Features in High Functioning Subjects With Pyridoxine-Dependent Epilepsy.

    PubMed

    Poliachik, Sandra L; Friedman, Seth D; Poliakov, Andrew V; Budech, Christopher B; Ishak, Gisele E; Shaw, Dennis W W; Gospe, Sidney M

    2016-01-01

    In this observational study, white matter structure, functional magnetic resonance imaging (fMRI) task-based responses, and functional connectivity were assessed in four subjects with high functioning pyridoxine-dependent epilepsy and age-matched control subjects. Four male subjects with pyridoxine-dependent epilepsy (mean age 31 years 8 months, standard deviation 12 years 3 months) and age-matched control subjects (32 years 4 months, standard deviation 13 years) were recruited to participate in the study. Diffusion tensor data were collected and postprocessed in Functional Magnetic Resonance Imaging of the Brain Software Library to quantify corpus callosum tracts as a means to assess white matter structure. Task-based fMRI data were collected and Functional Magnetic Resonance Imaging of the Brain Software Library used to assess task response. The fMRI resting-state data were analyzed with the functional connectivity toolbox Conn to determine functional connectivity. Subjects with high functioning pyridoxine-dependent epilepsy retained structural white matter connectivity compared with control subjects, despite morphologic differences in the posterior corpus callosum. fMRI task-based results did not differ between subjects with pyridoxine-dependent epilepsy and control subjects; functional connectivity as measured with resting-state fMRI was lower in subjects with pyridoxine-dependent epilepsy for several systems (memory, somatosensory, auditory). Although corpus callosum morphology is diminished in the posterior portions, structural connectivity was retained in subjects with pyridoxine-dependent epilepsy, while functional connectivity was diminished for memory, somatosensory, and auditory systems. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2011-01-01

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

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

    PubMed

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

    2008-01-01

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

  6. Sensation seeking as a common factor in opioid dependent subjects and high risk sport practicing subjects. A cross sectional study.

    PubMed

    Franques, P; Auriacombe, M; Piquemal, E; Verger, M; Brisseau-Gimenez, S; Grabot, D; Tignol, J

    2003-03-01

    Animal research has outlined a vulnerability trait to drug dependence like behavior. The behavioral characteristic of this vulnerability is hyperactivity in response to a novel environment of which sensation seeking (SS) has been suggested as a possible equivalent in humans. If this is the case, SS should be more frequent in drug dependent and risky sports practicing subjects then controls. The objective of this study was to determine if opioid dependent subjects (ODS) and regular paragliders (RP) would be more SS then normal controls. Cross sectional study. Three groups of 34 individuals (total 102) matched for age and sex were selected from ODS seeking treatment, a paragliding club, and a college staff. Global and sub-scores of the Zuckerman sensation seeking scale (SSS). Non parametric statistics (Kruskal Wallis and Wilcoxon 2-Sample Tests) were used given the non-normal distribution of SSS scores in the ODS and RP groups. Significant differences were found across the three groups for the Thrill and Adventure Seeking (TAS) (P = 0.001), dishinibition (Dis) (P = 0.0003) and total score (P = 0.001). ODS and RP scored significantly higher than controls on two (Dis and the TAS scales). RP also scored significantly higher on the Boredom Susceptibility (BS) scale (P = 0.04). Our results show that RP and ODS differ from controls and have some similarities based on the SSS. In this study, the ODS and the RP could express different forms of a general tendency to seek intense and abrupt sensations through various behaviors. Our results in humans are in favor of the hypothesis that the behavioral trait of vulnerability to drug dependence behavior is expressed through SS. Copyright 2002 Elsevier Science Ireland Ltd.

  7. 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.

  8. Meth math: modeling temperature responses to methamphetamine.

    PubMed

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

    2014-04-15

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

  9. Meth math: modeling temperature responses to methamphetamine

    PubMed Central

    Molkov, Yaroslav I.; Zaretskaia, Maria V.

    2014-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

    Jing, Li; Zhang, Yanan

    2015-01-01

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

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

    PubMed

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

    2014-10-31

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

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

    PubMed Central

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

    2017-01-01

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

  14. Subchronic apocynin treatment attenuates methamphetamine-induced dopamine release and hyperactivity in rats.

    PubMed

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

    2014-03-07

    The effects of methamphetamine are linked to stimulation of dopaminergic neurons, which can be accompanied by production of reactive oxygen species (ROS). Apocynin (4-hydroxy-3-methoxy-acetophenone) is a nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) inhibitor shown to mitigate oxidative stress in a number of models. The present study aimed at testing whether apocynin suppresses the dopamine-releasing and locomotor-activating properties of methamphetamine. (1) Apocynin (0.01-100μM) was applied to rat striatal slices preloaded with [(3)H]dopamine and its efficacy to evoke [(3)H]overflow and to alter methamphetamine (3μM)-evoked [(3)H]overflow was measured. (2) Groups of rats received apocynin (15 or 50mg/kg/day) or vehicle injection for seven consecutive days, and the efficacy and potency of methamphetamine to evoke [(3)H]overflow were determined. (3) Groups of apocynin-treated rats were administered methamphetamine (0.5 or 1mg/kg) or saline to determine the effect of apocynin on stimulant-induced hyperactivity. (1) Apocynin applied to striatal slices did not evoke [(3)H]overflow or alter methamphetamine-evoked [(3)H]overflow. (2) However, subchronic apocynin treatment significantly and dose-dependently decreased methamphetamine's potency and efficacy to evoke [(3)H]overflow. (3) Subchronic apocynin treatment also decreased the locomotor activity evoked by methamphetamine. Subchronic apocynin treatment diminished methamphetamine induced dopamine-release and its locomotor-activating properties. The pattern of results indicates that apocynin is more effective after repeated, rather than after acute, treatment. The findings also suggest that NOX inhibitors or agents suppressing oxidative stress may constitute a new area for research to understand how methamphetamine produces its deleterious and neurotoxic outcomes in the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects.

    PubMed

    Verdejo-Garcia, Antonio; Contreras-Rodríguez, Oren; Fonseca, Francina; Cuenca, Aida; Soriano-Mas, Carles; Rodriguez, Joan; Pardo-Lozano, Ricardo; Blanco-Hinojo, Laura; de Sola Llopis, Susana; Farré, Magí; Torrens, Marta; Pujol, Jesús; de la Torre, Rafael

    2014-03-01

    Cocaine addiction is characterized by persistent decision-making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine-dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting-state activation. Ten cocaine-dependent subjects and 14 non-drug-using controls participated in the study. Cocaine-dependent subjects were carefully selected to discard potentially confounding co-morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting-state. During the moral dilemmas task, cocaine-dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting-state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine-dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2012-09-01

    Unemployment rates are high among chronic methamphetamine (MA) users and carry a significant economic burden, yet little is known about the neurocognitive and psychiatric predictors of employment in this vulnerable population. The present study examined this issue in 63 participants with recent MA dependence and 47 comparison subjects without histories of MA use disorders. All participants completed a comprehensive neurocognitive, psychiatric and neuromedical evaluation. Individuals with HIV infection, severe neuropsychological or psychiatric conditions that might affect cognition (e.g., seizure disorder, schizophrenia), or a positive Breathalyzer or urine toxicology screen on the day of testing were excluded. Consistent with previous research, a logistic regression revealed MA dependence as a significant, independent predictor of full-time unemployment status. Within the MA-dependent sample, greater impairment in global neurocognitive functioning and history of injection drug use emerged as significant independent predictors of unemployment status. The association between worse global cognitive functioning and unemployment was primarily driven by deficits in executive functions, learning, verbal fluency, and working memory. These findings indicate that neurocognitive deficits play a significant role in the higher unemployment rates of MA-dependent individuals, and highlight the need for vocational rehabilitation and supported employment programs that assess and bolster cognitive skills in this population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Structural and metabolic brain changes in the striatum associated with methamphetamine abuse.

    PubMed

    Chang, Linda; Alicata, Daniel; Ernst, Thomas; Volkow, Nora

    2007-04-01

    To review structural, chemical and metabolic brain changes, particularly those in the basal ganglia, in individuals who used methamphetamine, as well as in children with prenatal methamphetamine exposure. Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies that evaluated brain structural, chemical and metabolite changes in methamphetamine subjects, or children with prenatal methamphetamine exposure, were reviewed and summarized. Relevant pre-clinical studies that provided insights to the interpretations of these imaging studies were also reviewed. In adults who used methamphetamine, MRI demonstrates enlarged striatal volumes, while MR spectroscopy shows reduced concentrations of the neuronal marker N-acetylasparate and total creatine in the basal ganglia. In contrast, children with prenatal methamphetamine exposure show smaller striatal structures and elevated total creatine. Furthermore, PET studies consistently showed reduced dopamine transporter (DAT) density and reduced dopamine D(2) receptors in the striatum of methamphetamine subjects. PET studies also found lower levels of serotonergic transporter density and vesicular monoamine transporter (VMAT2) across striatal subregions, as well as altered brain glucose metabolism that correlated with severity of psychiatric symptoms in the limbic and orbitofrontal regions. Neuroimaging studies demonstrate abnormalities in brain structure and chemistry convincingly in individuals who used methamphetamine and in children with prenatal methamphetamine exposure, especially in the striatum. However, many important questions remain and larger sample sizes are needed to validate these preliminary observations. Furthermore, longitudinal studies are needed to evaluate the effects of treatment and abstinence on these brain changes and to determine whether imaging, and possibly genetic, markers can be used to predict treatment outcome or relapse.

  19. MOP Reduction During Long-Term Methamphetamine Withdrawal was Restored by Chronic Post-Treatment with Fluoxetine.

    PubMed

    Yamamoto, H; Takamatsu, Y; Imai, K; Kamegaya, E; Hagino, Y; Watanabe, M; Yamamoto, T; Sora, I; Koga, H; Ikeda, K

    2011-03-01

    Previously, we found fluoxetine reduces methamphetamine preference in mice. However, effects of fluoxetine on developed methamphetamine preference and on methamphetamine induced gene expression changes have been largely unknown. The present study investigates effects of post-treatment with fluoxetine on methamphetamine dependence and on gene expressions after long-term withdrawal in mice. First, we examined whether chronic post-treatment with fluoxetine attenuated methamphetamine-conditioned place preference. Next, we examined the changes in gene expression levels after long-term withdrawal (with saline or fluoxetine treatment) following chronic methamphetamine treatment. Using mRNA from the pooled frontal cortices of 10 mice per group, gene expression analyses were performed using a custom-developed cDNA array and a real-time quantitative reverse transcription-PCR. Chronic post-treatments with fluoxetine abolished the conditioned place preference developed by methamphetamine administrations. Even after long-term withdrawal from repeated methamphetamine administration, µ-opioid receptor (MOP) gene expression was significantly reduced in the frontal cortex. The reduced MOP gene expression in the frontal cortex was restored by chronic administration with fluoxetine. These changes were confirmed by Western blot analyses. These findings suggest that the chronic post-treatments with fluoxetine might be effective for restoring the reduction of MOP levels in the frontal cortex following long-term abstinence from methamphetamine.

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

    PubMed Central

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

    2012-01-01

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

  1. A receptor mechanism for methamphetamine action in dopamine transporter regulation in brain.

    PubMed

    Xie, Zhihua; Miller, Gregory M

    2009-07-01

    This study reveals a novel receptor mechanism for methamphetamine action in dopamine transporter (DAT) regulation. Trace amine-associated receptor 1 (TAAR1) is expressed in brain dopaminergic nuclei and is activated by methamphetamine in vitro. Here, we show that methamphetamine interaction with TAAR1 inhibits [(3)H]dopamine uptake, enhances or induces [(3)H]dopamine efflux, and triggers DAT internalization. In time course assays in which methamphetamine and [(3)H]dopamine were concurrently loaded into cells or synaptosomes or in pretreatment assays in which methamphetamine was washed away before [(3)H]dopamine loading, methamphetamine caused a distinct inhibition in [(3)H]dopamine uptake in TAAR1 + DAT-cotransfected cells and in wild-type mouse and rhesus monkey striatal synaptosomes. This distinct uptake inhibition was not observed in DAT-only transfected cells or in TAAR1 knockout mouse striatal synaptosomes. In [(3)H]dopamine efflux assays using the same cell and synaptosome preparations, methamphetamine enhanced [(3)H]dopamine efflux at a high loading concentration of [(3)H]dopamine (1 muM) or induced [(3)H]dopamine efflux at a low loading concentration of [(3)H]dopamine (10 nM) in a TAAR1-dependent manner. In DAT biotinylation assays using the same cell and synaptosome preparations, we observed that 1 muM methamphetamine induced DAT internalization in a TAAR1-dependent manner. All these TAAR1-mediated effects of methamphetamine were blocked by the protein kinase inhibitors H89 [N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline] and/or 2-{8-[(dimethylamino) methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl}-3-(1-methylindol-3-yl)maleimide (Ro32-0432), suggesting that methamphetamine interaction with TAAR1 triggers cellular phosphorylation cascades and leads to the observed effects of methamphetamine on DAT. These findings demonstrate a mediatory role of TAAR1 in methamphetamine action in DAT regulation and implicate this receptor as a potential target of

  2. Bupropion differentially impacts acquisition of methamphetamine self-administration and sucrose-maintained behavior.

    PubMed

    Reichel, Carmela M; Linkugel, Jessica D; Bevins, Rick A

    2008-05-01

    Bupropion reduces the subjective effects and cue-induced craving for methamphetamine in humans. Given these effects of bupropion on methamphetamine in humans and its widespread clinical use, a preclinical model of drug-taking was used to determine if pretreatment with bupropion would alter the acquisition of methamphetamine self-administration. During acquisition, rats were given saline or bupropion (30 or 60 mg/kg, IP) 5 min before a 60-min session. For the first 8 days, each response on the active lever produced an infusion of methamphetamine (0.025 mg/kg). Responding on the inactive lever had no programmed consequence. This FR1 schedule was then increased to an FR3 for 4 more days. In a parallel study, the identical procedures were used to test the impact of bupropion on sucrose-maintained responding. Bupropion pretreatment decreased the number of methamphetamine infusions and sucrose deliveries earned on an FR1 and FR3. However, bupropion pretreatment only delayed discrimination between the active and inactive levers in the methamphetamine self-administration rats. Discrimination between active and inactive levers was acquired in all groups in the sucrose experiment regardless of pretreatment condition. Combined, these results suggest that bupropion has a more general effect within the appetitive/reward system of the brain rather than having complete specificity for methamphetamine.

  3. Bupropion differentially impacts acquisition of methamphetamine self-administration and sucrose-maintained behavior

    PubMed Central

    Reichel, Carmela M.; Linkugel, Jessica D.; Bevins, Rick A.

    2010-01-01

    Bupropion reduces the subjective effects and cue-induced craving for methamphetamine in humans. Given these effects of bupropion on methamphetamine in humans and its widespread clinical use, a preclinical model of drug-taking was used to determine if pretreatment with bupropion would alter the acquisition of methamphetamine self-administration. During acquisition, rats were given saline or bupropion (30 or 60 mg/kg, IP) 5 min before a 60-min session. For the first 8 days, each response on the active lever produced an infusion of methamphetamine (0.025 mg/kg). Responding on the inactive lever had no programmed consequence. This FR1 schedule was then increased to an FR3 for 4 more days. In a parallel study, the identical procedures were used to test the impact of bupropion on sucrose-maintained responding. Bupropion pretreatment decreased the number of methamphetamine infusions and sucrose deliveries earned on an FR1 and FR3. However, bupropion pretreatment only delayed discrimination between the active and inactive levers in the methamphetamine self-administration rats. Discrimination between active and inactive levers was acquired in all groups in the sucrose experiment regardless of pretreatment condition. Combined, these results suggest that bupropion has a more general effect within the appetitive/reward system of the brain rather than having complete specificity for methamphetamine. PMID:18329085

  4. Cerebellar gray matter volume correlates with duration of cocaine use in cocaine-dependent subjects.

    PubMed

    Sim, Minyoung E; Lyoo, In Kyoon; Streeter, Chris C; Covell, Julie; Sarid-Segal, Ofra; Ciraulo, Domenic A; Kim, Minue J; Kaufman, Marc J; Yurgelun-Todd, Deborah A; Renshaw, Perry F

    2007-10-01

    This study was conducted to explore differences in gray and white matter volume between cocaine-dependent and healthy comparison subjects using optimized voxel-based morphometry (VBM). Brain magnetic resonance imaging (MRI) and neuropsychological function tests were performed for 40 cocaine-dependent subjects (41.4+/-6.9 years, 27 men) and 41 healthy age- and sex-matched comparison subjects (38.7+/-8.8 years, 26 men). Optimally normalized whole brain MR images were segmented, modulated, smoothed, and compared between groups with statistical parametric mapping. The cocaine-dependent group had lower gray matter volumes in bilateral premotor cortex (Brodmann area (BA) 6, 8; 16.6%), right orbitofrontal cortex (BA 10, 15.1%), bilateral temporal cortex (BA 20, 38; 15.9%), left thalamus (12.6%), and bilateral cerebellum (13.4%) as well as lower right cerebellar white matter volume (10.0%) relative to the comparison group at a corrected p<0.05 for multiple comparisons. Duration of cocaine use negatively correlated with right and left cerebellar gray matter volumes (r=-0.37, r=-0.39, respectively). In cocaine-dependent subjects, lower cerebellar hemispheric gray and white matter volumes were correlated with deficits in executive function and decreased motor performance. This study reports that cocaine-dependent subjects have lower gray matter volumes in cerebellar hemispheres as well as in frontal, temporal cortex, and thalamus. These findings are the first to suggest that the cerebellum may be vulnerable to cocaine-associated brain volume changes, and that cerebellar deficits may contribute to neuropsychological deficits and motor dysfunction frequently observed in cocaine-dependent subjects.

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

    PubMed

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

    2004-09-01

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

  6. 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…

  7. Methamphetamine: Putting the Brakes on Speed

    ERIC Educational Resources Information Center

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

    2006-01-01