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Sample records for 42-year-old male methamphetamine

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

    PubMed Central

    Pan, Koushik

    2015-01-01

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

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

    PubMed

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

    2016-02-01

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

  3. Radiology Case of the Month: An Unusual Etiology of Increased Abdominal Girth in a 42-Year-Old Man.

    PubMed

    Patel, Anish; Han, Brian; Degeyter, Kyle; Neitzschman, Harold

    2015-01-01

    A 42-year-old man with diabetes and hypertension presented to the emergency room after experiencing a several month history of gradually increasing abdominal girth with the sudden onset of abdominal pain. PMID:27159604

  4. Methamphetamine

    MedlinePlus

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

  5. 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 ...

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

    PubMed

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

    2016-09-01

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

  7. 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.

  8. A 42-year-old farmer from Bangladesh with respiratory failure, septic arthritis, and multiple cavitating consolidations.

    PubMed

    AlShati, Mohammed H; Joshi, Rajinder M

    2014-08-01

    A 42-year-old man was directly admitted to the ICU with respiratory failure and hypotension. Two weeks prior and just after returning from Bangladesh, he presented to a polyclinic with fever, right knee pain, and generalized aches, for which he received oral antibiotics. He was a farmer, had diabetes, never smoked, and consumed alcohol occasionally.

  9. 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 ...

  10. Methamphetamine

    MedlinePlus

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

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

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

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

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

    PubMed

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

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

  13. [A 42-year-old farmer with nonspecific leucocytosis and elevated transaminases. Acute septic reaction in Coxiella burnetii infection].

    PubMed

    Hempel, U; Schäffler, A; Salzberger, B; Rümmele, P; Schölmerich, J

    2008-06-01

    We report about a 42-year-old farmer with leucocytosis, elevation of transaminases and liver cirrhosis as an underlying condition. The diagnosis of Q fever hepatitis was made through liver biopsy and serology. Under therapy with doxycycline, transaminases initially increased again; after switching to ciprofloxacin, the patient could be discharged 3 weeks after admission. Q fever is caused by Coxiella burnetii. The most frequent acute manifestation is a self-limiting flu-like illness. Chronic Q fever mostly presents as endocarditis. The diagnosis is made through histology ("doughnut" granulomas), PCR, serology (acute: anti-phase II antibodies, chronic: anti-phase I antibodies) and culture. Standard therapy is doxycycline.

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

    PubMed

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

    2009-07-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Hensleigh, Emily; Pritchard, Laurel M

    2015-12-15

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. 96-hour methamphetamine self-administration in male and female rats: a novel model of human methamphetamine addiction.

    PubMed

    Cornett, Elyse M; Goeders, Nicholas E

    2013-10-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

    Schwienteck, Kathryn L.; Banks, Matthew L.

    2015-01-01

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

  2. Impact of prenatal and acute methamphetamine exposure on behaviour of adult male rats.

    PubMed

    Schutová, B; Hrubá, L; Pometlová, M; Slamberová, R

    2009-01-01

    Psychostimulants have been shown to alter behaviour in both rats and humans. The aim of the present study was: (1) to assess the effect of prenatal and acute methamphetamine (MA) administration on behaviour in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood. Behaviour of adult male rats prenatally exposed to MA (5 mg/kg) or no drug was tested in Open field (OF) and Elevated plus maze (EPM). Half of the animals were injected with MA (1 mg/kg) subcutaneously 30 minutes prior to testing. Locomotion, exploration, comforting behaviour and anxiety were evaluated in the OF, while anxiety and exploratory behaviour were assessed in the EPM. Our results showed that prenatal MA did not have an effect on baseline behaviour in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behaviour and decreasing comforting behaviour. Moreover, adult rats prenatally exposed to MA were more sensitive to the effects of acute MA on exploration. In addition, acute MA application decreased anxiety in the OF as well as in the EPM. Our present study, thus, demonstrates that acute MA increases overall psychomotor activity and decreases anxiety to novel environment. To further support our hypothesis that prenatal MA exposure increases sensitivity to drugs in adulthood, studies investigating the levels of dopamine in the rat brain after prenatal MA exposure are planned.

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

    PubMed

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

    2012-02-01

    Understanding sensory reinforcement and the effects of stimulant drugs on sensory reinforcers is potentially important for understanding their influence on addiction processes. Experiment 1 explored the reinforcing properties of a visual stimulus and the effects of methamphetamine (METH) on responding maintained by a visual reinforcer (VRF) in male rats. Snout poke responses to the active alternative produced the VRF according to variable interval (VI) schedules of reinforcement, and responses to an inactive alternative had no programmed effect. Experiment 2 explored the effects of METH on choice between the VRF and a water reinforcer (H2ORF) using concurrent VI schedules in male rats. In Experiment 1, response-contingent onset of the VRF produced an increase in both the relative frequency and absolute rate of active responding. The rate of both active and inactive responding declined across the 40-min test sessions. METH did not differentially enhance active responding for the VRF. Instead, METH nondifferentially increased the rate of responding and attenuated the within-session decline of responding. In Experiment 2, METH differentially increased the rate of responding for the VRF relative to the H2ORF. The results of these exploratory experiments indicate that the reinforcing effects of the VRF were weak and transient. In addition, METH treatment increased responding, and the specificity of the enhancement of METH was dependent upon the testing conditions. Potential explanations of these differences, such as novelty and reinforcer type, are discussed. PMID:21942261

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

    PubMed

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

    2012-02-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-10-10

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

  7. Effect of methamphetamine exposure and cross-fostering on cognitive function in adult male rats.

    PubMed

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

    2010-03-17

    The aim of our study was to examine the effect of prenatal methamphetamine (MA) exposure and cross-fostering on cognitive functions of adult male rats tested in Morris water maze (MWM). Rat mothers were exposed daily to injection of MA (5mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Females without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised 4 pups of her own and 8 pups from the mothers with the other two treatments. Four types of tests were used: (1) Place navigation test (Learning), (2) Probe test (Probe), (3) Retention memory test (Memory) and (4) Visible platform task. Our results demonstrate that the prenatal exposure to MA does not impact learning and memory, while postnatal exposure to MA shows impairments in cognition. In the test of learning, all animals fostered to MA-treated dams had longer latencies, bigger search error and used lower spatial strategies than the animals fostered to control or saline-treated mother, regardless of prenatal exposure. Regardless of postnatal exposure, the animals prenatally exposed to saline swam faster in all the tests than the animals prenatally exposed to MA and controls, respectively. This study indicates that postnatal but not prenatal exposure to MA affects learning in adult male rats. However, it is still not clear whether these impairments are due to a direct effect of MA on neuronal structure or due to an indirect effect of MA mediated by impaired maternal care.

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

    PubMed

    Bolin, B Levi; Akins, Chana K

    2012-10-01

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

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

    PubMed

    Naidoo, S; Smit, D

    2011-04-01

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

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

    PubMed

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

    2016-05-30

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

  11. Nicotine and Methamphetamine Disrupt Habituation of Sensory Reinforcer Effectiveness in Male Rats

    PubMed Central

    Lloyd, David R.; Hausknecht, Kathryn A.; Richards, Jerry B.

    2014-01-01

    The reinforcing effectiveness of a sensory stimulus such as light-onset rapidly habituates (Lloyd, Gancarz, Ashrafioun, Kausch, & Richards, 2012). According to memory-based theories, habituation occurs if a memory exists for perceived stimulation, and dishabituation occurs if a memory does not exist and the stimulation is “unexpected.” According to Redgrave and Gurney (2006), unexpected response-contingent sensory stimuli increase phasic firing of dopamine neurons, providing a sensory error signal that reflects the difference between perceived and expected stimuli. Together, memory-based theories of habituation and the sensory error signal hypothesis predict a disruption (slowing) of habituation rate by novel response-contingent sensory stimulation or by artificial increases in dopamine neurotransmission by stimulant drugs. To test these predictions, we examined the effects of stimulant drugs on both the operant level of responding (snout-poking) and operant responding for a sensory reinforcer (light-onset) presented according to a fixed ratio 1 schedule. Robust within-session decreases in responding indicating habituation were observed. The effects of stimulant drugs (saline, n = 10; nicotine, 0.40 mg/kg, n = 10; and methamphetamine, 0.75 mg/kg, n = 9) on habituation in rats were determined. Nicotine was found to decrease habituation rate and did not affect response rate, while methamphetamine decreased habituation rate and increased response rate. In addition, introduction of a novel visual stimulus reinforcer decreased habituation rate and increased responding. These findings show that habituation of reinforcer effectiveness modulates operant responding for sensory reinforcers, and that stimulant drugs may disrupt normally occurring habituation of reinforcer effectiveness by increasing dopamine neurotransmission. PMID:24708147

  12. Nicotine and methamphetamine disrupt habituation of sensory reinforcer effectiveness in male rats.

    PubMed

    Lloyd, David R; Hausknecht, Kathryn A; Richards, Jerry B

    2014-04-01

    The reinforcing effectiveness of a sensory stimulus such as light-onset rapidly habituates (Lloyd, Gancarz, Ashrafioun, Kausch, & Richards, 2012). According to memory-based theories, habituation occurs if a memory exists for perceived stimulation, and dishabituation occurs if a memory does not exist and the stimulation is "unexpected." According to Redgrave and Gurney (2006), unexpected response-contingent sensory stimuli increase phasic firing of dopamine neurons, providing a sensory error signal that reflects the difference between perceived and expected stimuli. Together, memory-based theories of habituation and the sensory error signal hypothesis predict a disruption (slowing) of habituation rate by novel response-contingent sensory stimulation or by artificial increases in dopamine neurotransmission by stimulant drugs. To test these predictions, we examined the effects of stimulant drugs on both the operant level of responding (snout-poking) and operant responding for a sensory reinforcer (light-onset) presented according to a fixed ratio 1 schedule. Robust within-session decreases in responding indicating habituation were observed. The effects of stimulant drugs (saline, n = 10; nicotine, 0.40 mg/kg, n = 10; and methamphetamine, 0.75 mg/kg, n = 9) on habituation in rats were determined. Nicotine was found to decrease habituation rate and did not affect response rate, while methamphetamine decreased habituation rate and increased response rate. In addition, introduction of a novel visual stimulus reinforcer decreased habituation rate and increased responding. These findings show that habituation of reinforcer effectiveness modulates operant responding for sensory reinforcers, and that stimulant drugs may disrupt normally occurring habituation of reinforcer effectiveness by increasing dopamine neurotransmission.

  13. Methamphetamine: Glossary

    MedlinePlus

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

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

    PubMed

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

    2016-06-01

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

  15. Methamphetamine (Meth)

    MedlinePlus

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

  16. [Methamphetamine, cannabis].

    PubMed

    Naruse, Nobuya

    2015-09-01

    The persons with marijuana abuse tend to be increasing in Japan, although illegal drugs use in lifetime is remarkably lower than other advanced countries, Europe and USA. In addition, there have been many methamphetamine users in Japan. As use of methamphetamine induces psychotic states, we recognize them as one of the key illegal drugs for clinical psychiatrists. Regarding to diagnosis of methamphetamine psychosis, there is a large difference between Japanese psychiatrists and other advanced countries' ones. The former considers that they have persistent symptoms. In contrast, the latter embraces it as the model of acute toxicosis. The Japanese government has been based on a full commitment to the crackdown on drug problems. However, they will execute the new law in 2016, in which some persons charged with violating the methamphetamine control law will be adapted to partially probation on drug charges. Then, we have to improve our therapeutic and recovery supports to charged illegal drug users as rapidly as possible.

  17. Mind Over Matter: Methamphetamine

    MedlinePlus

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

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

    PubMed

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

    2016-08-01

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

  19. Predictors of cardiovascular response to methamphetamine administration in methamphetamine-dependent individuals.

    PubMed

    Fleury, Gilles; De La Garza, Richard; Mahoney, James J; Evans, Sarah E; Newton, Thomas F

    2008-01-01

    The goal of the present investigation was to determine predictors of cardiovascular response to methamphetamine administrated in the laboratory. Heart rate (HR) and blood pressure (BP) were measured at baseline and at several time points following the administration of methamphetamine or saline placebo. One-way ANOVA was used to determine the differences between female and male subjects in their cardiovascular response. In male subjects, linear regression and one-way ANOVA were used to determine the influence of potential predictors on cardiovascular response, including age, weight, drug use indicators, concurrent use of other substances, route of administration, and race. Methamphetamine administration provoked significant increases in HR and BP, as compared to placebo. Female gender was associated with larger peak change in diastolic BP following administration. Baseline HR and BP were found to be strong predictors of cardiovascular response to methamphetamine administration in male subjects. Lifetime use and recent use of methamphetamine and nicotine did not predict cardiovascular response to methamphetamine. Recent alcohol use was associated with increased peak change in diastolic BP. Also, current use of cannabis was negatively correlated with peak HR change. Male cannabis users show lower peak change in HR as compared to non-cannabis users. As compared to methamphetamine smokers, intravenous users demonstrated higher peak change in diastolic BP following drug administration. Race did not have a significant effect on cardiovascular response. Taken together, these findings may help in the prevention and treatment of cardiovascular events in a population at high risk of premature morbidity and mortality.

  20. Predictors of cardiovascular response to methamphetamine administration in methamphetamine-dependent individuals.

    PubMed

    Fleury, Gilles; De La Garza, Richard; Mahoney, James J; Evans, Sarah E; Newton, Thomas F

    2008-01-01

    The goal of the present investigation was to determine predictors of cardiovascular response to methamphetamine administrated in the laboratory. Heart rate (HR) and blood pressure (BP) were measured at baseline and at several time points following the administration of methamphetamine or saline placebo. One-way ANOVA was used to determine the differences between female and male subjects in their cardiovascular response. In male subjects, linear regression and one-way ANOVA were used to determine the influence of potential predictors on cardiovascular response, including age, weight, drug use indicators, concurrent use of other substances, route of administration, and race. Methamphetamine administration provoked significant increases in HR and BP, as compared to placebo. Female gender was associated with larger peak change in diastolic BP following administration. Baseline HR and BP were found to be strong predictors of cardiovascular response to methamphetamine administration in male subjects. Lifetime use and recent use of methamphetamine and nicotine did not predict cardiovascular response to methamphetamine. Recent alcohol use was associated with increased peak change in diastolic BP. Also, current use of cannabis was negatively correlated with peak HR change. Male cannabis users show lower peak change in HR as compared to non-cannabis users. As compared to methamphetamine smokers, intravenous users demonstrated higher peak change in diastolic BP following drug administration. Race did not have a significant effect on cardiovascular response. Taken together, these findings may help in the prevention and treatment of cardiovascular events in a population at high risk of premature morbidity and mortality. PMID:18393052

  1. 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

  2. Research Reports: Methamphetamine

    MedlinePlus

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

  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.

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

    PubMed Central

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

    2015-01-01

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

  5. 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.

  6. Methamphetamine use and sexual and injection risk behaviors among out-of-treatment injection drug users.

    PubMed

    Molitor, F; Ruiz, J D; Flynn, N; Mikanda, J N; Sun, R K; Anderson, R

    1999-08-01

    Our primary objective was to examine the relationship between methamphetamine use and sexual risk-taking behaviors--number of sexual partners, frequency of sexual behaviors with regular and casual partners, trading money or drugs for sex, and condom use--among male and female out-of-treatment injection drug users (OTIDUs). As a risk group for human immunodeficiency virus (HIV) transmission, we also investigated injection behaviors by methamphetamine use. Data were collected from 1392 OTIDUs within the California counties of Fresno, Sacramento, and San Diego. Excluded from this cross-sectional survey were male OTIDUs engaging in sex with only or mostly men since 1978. In bivariate analyses, we found that male OTIDUs with a history of methamphetamine use had more sex partners and participated in more acts of anal insertive intercourse with casual partners and vaginal intercourse with regular and casual partners than male OTIDUs never using methamphetamines. In addition, a greater percentage of male OTIDUs using methamphetamines reported trading sex for money or drugs. Methamphetamine-using female OTIDUs participated in more acts of vaginal intercourse with regular male sex partners than female OTIDUs never using methamphetamines. By multivariate logistic regression, we found methamphetamine use related to consistent condom use among male OTIDUs and among male sex partners of female OTIDUs. Discriminant function analyses revealed that sexual risk taking could be differentiated by methamphetamine use among male OTIDUs. Methamphetamine use also correlated with using shared needles or syringes among male and female OTIDUs and was related to not always disinfecting used needles or syringes with bleach. Our findings suggest that methamphetamines may contribute to heterosexual HIV transmission.

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

    PubMed

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

    2011-01-20

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

  8. Dopamine D(3) receptor antagonist SB-277011A inhibits methamphetamine self-administration and methamphetamine-induced reinstatement of drug-seeking in rats.

    PubMed

    Higley, Amanda E; Kiefer, Stephen W; Li, Xia; Gaál, József; Xi, Zheng-Xiong; Gardner, Eliot L

    2011-06-01

    We have previously reported that selective blockade of brain dopamine D(3) receptors by SB-277011A significantly attenuates cocaine self-administration and cocaine-induced reinstatement of drug-seeking behavior. In the present study, we investigated whether SB-277011A similarly inhibits methamphetamine self-administration and methamphetamine-induced reinstatement to drug-seeking behavior. Male Long-Evans rats were allowed to intravenously self-administer methamphetamine (0.05 mg/kg/infusion) under fixed-ratio 2 (FR2) or progressive-ratio (PR) reinforcement conditions, and some rats were tested for methamphetamine-induced reinstatement of drug-seeking behavior after extinction of self-administration. The effects of SB-277011A on each of these methamphetamine-supported behaviors were then tested. Acute intraperitoneal (i.p.) administration of SB-277011A failed to alter methamphetamine self-administration under FR2 reinforcement, but significantly lowered the break-point for methamphetamine self-administration under PR reinforcement. SB-277011A also significantly inhibited methamphetamine-triggered reinstatement of extinguished drug-seeking behavior. Overall, these data show that blockade of dopamine D(3) receptors by SB-277011A attenuates the rewarding and incentive motivational effects of methamphetamine in rats, supporting the development of selective dopamine D(3) antagonists for the treatment of methamphetamine addiction.

  9. 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

  10. 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

  11. 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

  12. Methamphetamine/Dextroamphetamine and Pregnancy

    MedlinePlus

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

  13. The Cardiac Complications of Methamphetamines.

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2007-01-01

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

  15. NAN-190, a possible specific antagonist for methamphetamine.

    PubMed

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

    2005-03-01

    Effect of NAN-190, a selective 5-HT(1A) receptor antagonist, on methamphetamine-induced locomotor activity, anorexia, analgesia, and hyperthermia was investigated in male mice. Methamphetamine (1.5 mg/kg, i.p) produced a significant increase in locomotor activity, which was significantly antagonized by NAN-190 at a dose of 4 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone. Methamphetamine (2 mg/kg, i.p) produced a significant decrease in food intake of mice, which were deprived of food during the previous 24h. This anorectic activity of methamphetamine was significantly antagonized by NAN-190 at a dose of 2 mg/kg, i.p. NAN-190 did not alter the food intake of mice when it was administered alone. Methamphetamine (2 mg/kg, i.p) also produced a significant increase in body temperature of mice, which was significantly antagonized by NAN-190 at a dose of 0.5 mg/kg, i.p. NAN-190 did not alter the body temperature of mice when it was administered alone. In the writhing test, methamphetamine (1 mg/kg, i.p) produced a significant antinociceptive effect in mice. This was significantly antagonized by NAN-190 at a dose of 1 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the above-studied activities of methamphetamine in mice. This role is possibly mediated through direct stimulation of the 5-HT(1A) receptor subtype. All of the above-studied activities of methamphetamine were antagonized by NAN-190, which may indicate that NAN-190 is a possible antagonist for methamphetamine.

  16. Developmental neurotoxicity to methamphetamines.

    PubMed

    Weissman, A D; Caldecott-Hazard, S

    1995-05-01

    1. To investigate the long-term changes caused by amphetamines in the developing brain, we used both an in vivo and in vitro model of chronic fetal exposure to methamphetamine and related drugs. 2. Offspring of rats, treated with either saline, 2 mg/kg twice a day (b.i.d.) or 10 mg/kg b.i.d. methamphetamine throughout gestation, were examined at 30 days of age for changes in the monoamine system of their brains. 3. At the lower dose methamphetamine was neurotoxic to specific neuronal populations, mostly serotonergic. At the higher dose, methamphetamine retained its neurotoxic properties, but also stimulated the growth of axonal terminals in specific regions as evidenced by an increase in monoamine uptake sites. The neurochemical changes at the higher dose were correlated with deficits in adult behavioural measures. 4. Corresponding in vitro drug treatments of rat neuroblastomas cells also produced a dose-related effect on cellular growth and differentiation patterns. Neurotoxic as well as stimulatory effects of methamphetamine and some related compounds were seen in culture. 5. Our in vivo and in vitro observations demonstrate neurotoxic effects of amphetamines and the remodelling of synaptic morphology in response.

  17. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  20. A comparison of methylphenidate-, amphetamine-, and methamphetamine-induced hyperthermia and neurotoxicity in male Sprague-Dawley rats during the waking (lights off) cycle.

    PubMed

    Levi, Mark S; Divine, Becky; Hanig, Joseph P; Doerge, Daniel R; Vanlandingham, Michelle M; George, Nysia I; Twaddle, Nathan C; Bowyer, John F

    2012-03-01

    Previous studies focusing on amphetamine (AMPH), methamphetamine (METH) and methylphenidate (MPH) neurotoxicity have almost exclusively been conducted in rodents during the light cycle, which is when most rodents sleep. There are virtually no studies that have simultaneously compared the effects of these three stimulants on body temperature and also determined serum stimulant levels during exposure. The present study compared the effects of MPH, AMPH and METH treatment on body temperature and neurotoxicity during the waking (dark) cycle of the rat. This was done to more effectively replicate stimulant exposure in waking humans and to evaluate the relative risks of the three stimulants when taken inappropriately or non-therapeutically (e.g., abuse). Four subcutaneous injections (4×), at 2 h intervals, were used to administer each dose of the stimulants tested. Several equimolar doses for the three stimulants were chosen to produce plasma levels ranging from 3 times the highest therapeutic levels (no effect on body temperature) to those only attained by accidental overdose or intentional abuse in humans. Either 4×2.0 mg/kg AMPH or 4×2.2 mg/kg METH administered during the waking cycle resulted in peak serum levels of between 1.5 and 2.5 μM (4 to 5 times over maximum therapeutic levels of METH and AMPH) and produced lethal hyperthermia, 70% striatal dopamine depletions, and neurodegeneration in the cortex and thalamus. These results show that METH and AMPH are equipotent at producing lethal hyperthermia and neurotoxicity in laboratory animals during the wake cycle. Administration of either 4×2.2 or 4×3.3 mg/kg METH during the sleep cycle produced lower peak body temperatures, minimal dopamine depletions and little neurodegeneration. These findings indicate that administration of the stimulant during the waking cycle compared to sleep cycle may significantly increase the potency of amphetamines to produce hyperthermia, neurotoxicity and lethality. In contrast

  1. Methamphetamine and paranoia: the methamphetamine experience questionnaire.

    PubMed

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

    2010-01-01

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

  2. 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

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

    PubMed

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

    2011-01-01

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

  4. 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

  5. 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

  6. Methamphetamine Psychosis: Epidemiology and Management

    PubMed Central

    Glasner-Edwards, Suzette; Mooney, Larissa J.

    2016-01-01

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

  7. Effect of 7-nitroindazole on body temperature and methamphetamine-induced dopamine toxicity.

    PubMed

    Callahan, B T; Ricaurte, G A

    1998-08-24

    The present study was undertaken to examine the role of temperature on the ability of 7-nitroindazole (7-NI) to prevent methamphetamine-induced dopamine (DA) neurotoxicity. Male Swiss-Webster mice received methamphetamine alone or in combination with 7-NI at either room temperature (20+/-1 degrees C) or at 28+/-1 degrees C. At 20+/-1 degrees C, 7-NI produced hypothermic effects and afforded total protection against methamphetamine-induced DA depletions in the striatum. At 28+/-1 degrees C, 7-NI produced minimal effects on body temperature and failed to prevent methamphetamine-induced DA reductions. These findings indicate that the neuroprotection afforded by 7-NI is likely related to its ability to produce hypothermia because agents that produce hypothermia and/or prevent hyperthermia are known to attenuate methamphetamine-induced neurotoxicity.

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

    PubMed

    Hensleigh, E; Pritchard, L M

    2014-07-15

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-04-01

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

  11. 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. PMID:27345417

  12. 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.

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

    ERIC Educational Resources Information Center

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

    2000-01-01

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

  14. Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice.

    PubMed

    Chen, H H; Yang, Y K; Yeh, T L; Cherng, C F G; Hsu, H C; Hsiao, S Y; Yu, L

    2003-12-31

    Ovarian hormones were well documented to modulate the dopamine release in the central dopaminergic systems. The dopamine-releasing effects in the nucleus accumbens, a major target of the mesolimbicortical dopaminergic system, were closely associated with the reinforcing effects of two psychomotor stimulants, cocaine and methamphetamine. This study aimed to examine the sex differences in the cocaine- and methamphetamine-reinforcing behavior, conditioned place preference. In addition, the modulating effects of estradiol and progesterone on methamphetamine-induced conditioned place preference were investigated in both sexes of adult gonadectomized mice. There was no sex difference in the sensitivity to the cocaine (5 mg/kg)-induced conditioned place preference. However, female mice exhibited a more potent methamphetamine (1 mg/kg)-induced conditioned place preference than did male mice. Moreover, pretreatment with estradiol for two consecutive days before the beginning of the conditioning and throughout the four daily conditionings (0.47 microg/day for totally six days) effectively facilitated methamphetamine-induced conditioned place preference in gonadectomized female mice, but not in gonadectomized male mice. Progesterone, under a similar treatment regimen (0.47 microg/day for six consecutive days), did not alter the methamphetamine-induced conditioned place preference in either sex of gonadectomized mice. Taken together, we conclude that the facilitating effects of estradiol on methamphetamine-induced conditioned place preference could be sex-dependent with an eminent sensitivity associated with the adult female mice.

  15. 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

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

    PubMed Central

    Ahmadi, Jamshid; Ekramzadeh, Sara; Pridmore, Saxby

    2015-01-01

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

  17. Varied access to intravenous methamphetamine self-administration differentially alters adult hippocampal neurogenesis

    PubMed Central

    Mandyam, Chitra D.; Wee, Sunmee; Crawford, Elena F.; Eisch, Amelia J.; Richardson, Heather N.; Koob, George F.

    2008-01-01

    Background Chronic abuse of methamphetamine produces deficits in hippocampal function, perhaps by altering hippocampal neurogenesis and plasticity. We examined how intravenous methamphetamine self-administration modulates active division, proliferation of late progenitors, differentiation, maturation, survival, and mature phenotype of hippocampal subgranular zone (SGZ) progenitors. Methods Adult male Wistar rats were given access to methamphetamine 1 h twice weekly (intermittent short), 1 h daily (short), or 6 h daily (long). Rats received one intraperitoneal injection of bromodeoxyuridine (BrdU) to label progenitors in the synthesis (S) phase, and 28-day-old surviving BrdU-immunoreactive (IR) cells were quantified. Ki-67, doublecortin (DCX), and activated caspase-3 (AC-3) were used to visualize and quantify proliferating, differentiating, maturing, and apoptotic cells. Terminal corticosterone was measured to determine changes in adrenal steroids. Results Intermittent access to methamphetamine increased Ki-67 and DCX-IR cells, but opposing effects on late progenitors and postmitotic neurons resulted in no overall change in neurogenesis. Daily access to methamphetamine decreased all studied aspects of neurogenesis and reduced hippocampal granule neurons and volume, changes that likely are mediated by decreased proliferative and neurogenic capacity of the SGZ. Furthermore, methamphetamine self-administration relative to the amount of methamphetamine intake produced a biphasic effect on hippocampal apoptosis and reduced corticosterone levels. Conclusions Intermittent (occasional access) and daily (limited and extended access) self-administration of methamphetamine impact different aspects of neurogenesis, the former producing initial pro-proliferative effects and the latter producing downregulating effects. These findings suggest that altered hippocampal integrity by even modest doses of methamphetamine could account for pronounced pathology linked to methamphetamine

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

    PubMed

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

    2008-02-01

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

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

    PubMed Central

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

    2009-01-01

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

  20. Impulsivity and methamphetamine use.

    PubMed

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

    2005-09-01

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

  1. Methamphetamine Trends in the United States

    MedlinePlus

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

  2. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    MedlinePlus

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

  3. Prenatal Methamphetamine Exposure Linked with Problems

    MedlinePlus

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

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

    PubMed

    Rusch, Melanie L; Lozada, Remedios; Pollini, Robin A; Vera, Alicia; Patterson, Thomas L; Case, Patricia; Strathdee, Stefanie A

    2009-09-01

    Tijuana is situated on the Mexico-USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006-2007, IDUs > or =18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression was used to assess associations with methamphetamine use (past 6 months), stratified by gender. Among 1,056 participants, methamphetamine use was more commonly reported among females compared to males (80% vs. 68%, p < 0.01), particularly, methamphetamine smoking (57% vs. 34%; p < 0.01). Among females (N = 158), being aged >35 years (AOR, 0.2; 95% CI, 0.1-0.6) was associated with methamphetamine use. Among males (N = 898), being aged >35 years (AOR, 0.5; 95% CI, 0.3-0.6), homeless (AOR, 1.4 (0.9-2.2)), and ever reporting sex with another male (MSM; AOR, 1.9; 95% CI, 1.4-2.7) were associated with methamphetamine use. Among males, a history of MSM was associated with injection, while sex trade and >2 casual sex partners were associated with multiple routes of administration. HIV was higher among both males and females reporting injection as the only route of methamphetamine administration. Methamphetamine use is highly prevalent among IDUs in Tijuana, especially among females. Routes of administration differed by gender and subgroup which has important implications for tailoring harm reduction interventions and drug abuse treatment. PMID:19521780

  5. Methamphetamine induces the release of endothelin.

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Methamphetamines pretreatment and the vulnerability of the striatum to methamphetamine neurotoxicity.

    PubMed

    Stephans, S; Yamamoto, B

    1996-06-01

    Pretreatment with intermittent low-dose administrations of stimulants increases mesostriatal dopamine transmission upon administration of a challenge dose. This occurs without evidence of a long-term dopamine or serotonin depletion. The purpose was to examine whether pretreatment with low doses of methamphetamine enhances dopamine and/or glutamate efflux and the subsequent depletion of dopamine and serotonin produced by neurotoxic challenge doses of methamphetamine. Microdialysis was used to measure simultaneously extracellular concentrations of dopamine and glutamate in the striatum and prefrontal cortex of awake rats. Basal extracellular concentrations of dopamine and glutamate were unaltered following pretreatment with methamphetamine. The increase in methamphetamine-induced striatal dopamine efflux was not significantly different between methamphetamine and saline pretreated groups. In contrast, after high challenge doses of methamphetamine, dopamine efflux in prefrontal cortex was enhanced to a greater extent in methamphetamine pretreated rats as compared to saline pretreated controls. Acute methamphetamine did not enhance glutamate efflux in prefrontal cortex after pretreatment with saline or methamphetamine. The increase in striatal glutamate efflux was blunted in rats pretreated with methamphetamine. When measured 4 days later, dopamine and serotonin content in striatum was depleted in all rats acutely challenged with methamphetamine. However, these depletions were attenuated in rats pretreated with methamphetamine. An acute methamphetamine challenge did not affect dopamine tissue content in the prefrontal cortex of any rats. Serotonin content in cortex was depleted in all groups following the methamphetamine challenge administration, but these depletions were diminished in methamphetamine-pretreated rats. These results are the first evidence that an intermittent pretreatment regimen with low doses of methamphetamine, followed by a 1 week withdrawal

  9. Maxillary sinus manifestations of methamphetamine abuse.

    PubMed

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

    2015-01-01

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

  10. Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity.

    PubMed

    LaVoie, Matthew J; Card, J Patrick; Hastings, Teresa G

    2004-05-01

    Previous studies have demonstrated methamphetamine (METH)-induced toxicity to dopaminergic and serotonergic axons in rat striatum. Although several studies have identified the nature of reactive astrogliosis in this lesion model, the response of microglia has not been examined in detail. In this investigation, we characterized the temporal relationship of reactive microgliosis to neuropathological alterations of dopaminergic axons in striatum following exposure to methamphetamine. Adult male Sprague-Dawley rats were administered a neurotoxic regimen of methamphetamine and survived 12 h, or 1, 2, 4, and 6 days after treatment. Immunohistochemical methods were used to evaluate reactive changes in microglia throughout the brain of methamphetamine-treated rats, with a particular focus upon striatum. Pronounced morphological changes, indicative of reactive microgliosis, were evident in the brains of all methamphetamine-treated animals and were absent in saline-treated control animals. These included hyperplastic changes in cell morphology that substantially increased the size and staining intensity of reactive microglia. Quantitative analysis of reactive microglial changes in striatum demonstrated that these changes were most robust within the ventrolateral region and were maximal 2 days after methamphetamine administration. Analysis of tissue also revealed that microglial activation preceded the appearance of pathological changes in striatal dopamine fibers. Reactive microgliosis was also observed in extra-striatal regions (somatosensory and piriform cortices, and periaqueductal gray). These data demonstrate a consistent, robust, and selective activation of microglia in response to methamphetamine administration that, at least in striatum, precedes the appearance of morphological indicators of axon pathology. These observations raise the possibility that activated microglia may contribute to methamphetamine-induced neurotoxicity.

  11. Methamphetamines and Pregnancy Outcomes

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  13. Methamphetamine Use and Oral Health

    MedlinePlus

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

  14. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  15. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

    Objective: To investigate whether methamphetamine use is associated with sexual risk behavior among adolescents. Method: A cross-sectional survey of 1,561 male and female high school students in Cape Town (mean age 14.9 years) was conducted using items from the Problem Oriented Screening Instrument for Teenagers (POSIT) HIV Risk Scale. Results:…

  17. Methamphetamine Use: Hazards and Social Influences.

    ERIC Educational Resources Information Center

    Wermuth, Laurie

    2000-01-01

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

  18. Need for Methamphetamine Programming in Extension Education

    ERIC Educational Resources Information Center

    Beaudreault, Amy R.; Miller, Larry E.

    2011-01-01

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

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

    PubMed

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

    2012-07-01

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

  20. 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.

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

    PubMed

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

    2015-09-01

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

  2. Neural Correlates of Craving in Methamphetamine Abuse

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Tar, M T; Martinez, L R; Nosanchuk, J D; Davies, K P

    2014-07-01

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

  4. Methamphetamine enhances sexual behavior in female rats.

    PubMed

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

    2011-06-01

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

  5. Methamphetamine. Stimulant of the 1990s?

    PubMed Central

    Derlet, R. W.; Heischober, B.

    1990-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  7. Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

    MedlinePlus

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

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

    PubMed Central

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

    2015-01-01

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

  9. The neurobiology of methamphetamine induced psychosis

    PubMed Central

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

    2014-01-01

    Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP) can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support MAP as a model for schizophrenia. PMID:25100979

  10. 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.

  11. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methamphetamine test system. 862.3610 Section 862...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3610 Methamphetamine test system. (a) Identification. A methamphetamine test system is a...

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    PubMed Central

    Hellem, Tracy L.; Sung, Young-Hoon; Shi, Xian-Feng; Pett, Marjorie A.; Latendresse, Gwen; Morgan, Jubel; Huber, Rebekah S.; Kuykendall, Danielle; Lundberg, Kelly J.; Renshaw, Perry F.

    2015-01-01

    Objective Depression among methamphetamine users is more prevalent in females than males, but gender specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. Methods Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8 week open label trial of 5 grams of daily creatine monohydrate and of these 14, eleven females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. Results The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t(9) = 2.905, p < .01, suggesting that creatine increased phosphocreatine levels. Also, a reduction in methamphetamine

  14. Chronic methamphetamine administration reduces histamine-stimulated phosphoinositide hydrolysis in mouse frontal cortex.

    PubMed

    Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko

    2003-01-24

    In the present study, it was hypothesized that in vivo pretreatment with repeated methamphetamine would alter the agonist-stimulated phosphoinositide hydrolysis in mouse frontal cortical slices. Male ICR mice that received the methamphetamine injection (1.0mg/kg, intraperitoneally) once a day for five consecutive days showed behavioral sensitization to the same dose of methamphetamine 5 days after the last injection of the initial chronic treatment regimen (test day 10). On test day 10, the reduction of histamine (0.1-1.0mM)-stimulated phosphoinositide hydrolysis in the mouse frontal cortex was observed. The reduction was specific to histamine, but not to norepinephrine (10 microM-0.1mM) or L-glutamate (0.1-0.5mM). The reduction occurred without any change in the expression level of histamine H(1) receptor mRNA. The reduction recovered 25 days after the last injection of the initial chronic treatment regimen (test day 30). The direct application to the slices of a pharmacologically effective concentration of methamphetamine in vitro (10 microM) did not alter the histamine signal transduction. The present results suggest that the reduction is probably one of neuroadaptations in the frontal cortex contributing to behavioral sensitization.

  15. Methamphetamine

    MedlinePlus

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

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

    PubMed

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

    2011-02-01

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

  17. Pharmacotherapy of Methamphetamine Addiction: An Update

    PubMed Central

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

    2008-01-01

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

  18. Accidental death via intravaginal absorption of methamphetamine.

    PubMed

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

    2014-06-01

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

  19. Methamphetamine use and HIV in relation to social cognition.

    PubMed

    Homer, Bruce D; Halkitis, Perry N; Moeller, Robert W; Solomon, Todd M

    2013-07-01

    The relation of methamphetamine abuse and HIV infection to social cognition (Reading the Mind in the Eyes Task and Faux Pas Recognition Task) was examined in men who have sex with men (N = 56): Of the methamphetamine users (n = 29), 19 were identified as HIV positive, and of the nonusers (n = 27), 13 were identified as HIV positive. Both methamphetamine use and HIV were associated with impaired performance on the Eyes Task (p < .05). Methamphetamine use was also associated with impaired performance on the Faux Pas Task (p < .05). These results link impaired social cognition to methamphetamine abuse and HIV infection.

  20. 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

  1. 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

  2. Relationship Between Methamphetamine Exposure and Matrix Metalloproteinase 9 Expression

    PubMed Central

    Liu, Yun; Brown, Sheketta; Shaikh, Jamaluddin; Fishback, James A.; Matsumoto, Rae R.

    2013-01-01

    The involvement of matrix metalloproteinase (MMP) 9 in methamphetamine-induced neurotoxicity was evaluated. Injection of mice with stimulant or toxic doses of methamphetamine up regulated MMP9 gene expression in the brain within 5 min. By 24 h, MMP9 gene expression returned to control levels in the stimulant-treated mice, but remained elevated in animals exposed to toxic doses of methamphetamine. Reductions in striatal dopamine levels, a marker of methamphetamine neurotoxicity, developed 1–7 days following methamphetamine exposure, but were not accompanied by concomitant changes in MMP9 gene expression. In MMP9 knock out mice, methamphetamine retained its ability to elicit neurotoxicity. The data suggest that MMP9 expression does not contribute to methamphetamine-induced neurotoxicity, and may instead be involved in remodeling of the nervous system. PMID:18766021

  3. Relationship between methamphetamine exposure and matrix metalloproteinase 9 expression.

    PubMed

    Liu, Yun; Brown, Sheketta; Shaikh, Jamaluddin; Fishback, James A; Matsumoto, Rae R

    2008-09-17

    The involvement of matrix metalloproteinase (MMP) 9 in methamphetamine-induced neurotoxicity was evaluated. Injection of mice with stimulant or toxic doses of methamphetamine upregulated MMP9 gene expression in the brain within 5 min. By 24 h, MMP9 gene expression returned to control levels in the stimulant-treated mice, but remained elevated in animals exposed to toxic doses of methamphetamine. Reductions in striatal dopamine levels, a marker of methamphetamine neurotoxicity, developed 1-7 days after methamphetamine exposure, but were not accompanied by concomitant changes in MMP9 gene expression. In MMP9 knockout mice, methamphetamine retained its ability to elicit neurotoxicity. The data suggest that MMP9 expression does not contribute to methamphetamine-induced neurotoxicity, and may instead be involved in remodeling of the nervous system. PMID:18766021

  4. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

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

    2013-10-01

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

  5. Identifying methamphetamine exposure in children

    PubMed Central

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

    2013-01-01

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

  6. Methamphetamine Exposure: A Rural Early Intervention Challenge

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  7. 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…

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Lindsay, Brianna; Albrecht, Jennifer; Terplan, Mishka

    2011-01-01

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

  10. Outcome of treatment in patients with methamphetamine poisoning in an Iranian tertiary care referral center

    PubMed Central

    Paydar, Parva; Sabzghabaee, Ali Mohammad; Paydar, Hooman; Eizadi-Mood, Nastaran; Joumaa, Ali

    2015-01-01

    Objective: Methamphetamine is the second most widely abused drug worldwide. We performed a study on the treatment outcome of acute methamphetamine intoxication in a referral tertiary care University hospital in Iran. Methods: In this hospital-based, retrospective study which was carried out from 2012 to 2013, medical records of all patients aged 18 to 65 years who were admitted with a reliable history and clinical diagnosis of acute methamphetamine intoxication were abstracted and analyzed. Patients’ data included gender, age, type and route of poisoning, clinical manifestations, duration of hospitalization, and the treatment outcome. ANOVA, Chi-square, and binary logistic regression statistical tests were used for data analysis. Findings: A total of 129 patients with a mean age of 30.70 ± 0.93 (mean ± standard error), including 111 (86%) males, had been fully evaluated. Most of the patients had intentional poisoning (93.7%). In 42.6% of patients, inhalation was the main route of exposure. Most of the patients had complete improvement without any complication (89.1%). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI] 1.006–1.099), suicide history (OR, 30.33; 95% CI 3.11–295.24), route of poisoning ([ingestion: OR, 0.21; 95% CI 0.05–0.87], [inhalation: OR, 0.19; 95% CI 0.04–0.78]), and pulmonary system manifestations (OR 1.84; 95% CI 1.15–2.93) were predictive in patients outcome (P < 0.05). Conclusion: Methamphetamine poisoning was more common in males with intentional poisoning. Age, past history of suicide, route of poisoning, and pulmonary manifestations on admission could be considered as important predictive factors in patients’ outcome. PMID:26312257

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

    PubMed

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

    2016-08-01

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

  12. Agmatine attenuates methamphetamine-induced conditioned place preference in rats.

    PubMed

    Thorn, David A; Winter, Jerrold C; Li, Jun-Xu

    2012-04-01

    The polyamine agmatine modulates a variety of behavioral effects including the abuse-related effects of opioids and has been proposed as a potential medication candidate for the treatment of opioid abuse. However, little is known of the effects of agmatine on the abuse-related effects of other drugs of abuse. This study examined the effects of agmatine on the rewarding effects of methamphetamine in rats using a conditioned place preference paradigm. Methamphetamine (0.1-1.0mg/kg) dose-dependently increased the time spent in methamphetamine-paired side (place preference). Agmatine, at doses that did not produce place preference or aversion (10-32mg/kg), significantly decreased the development of methamphetamine-induced place preference when agmatine was administered in combination with methamphetamine during place conditioning. Agmatine also significantly decreased the expression of methamphetamine-induced place preference when an acute injection of agmatine was given immediately before test session. These doses of agmatine do not alter the motor activity in rats, suggesting that the observed attenuation of methamphetamine-induced place preference was not due to general behavioral disruption. Together, these data suggests that agmatine attenuates the rewarding effects of methamphetamine and may be able to modulate the abuse liability of methamphetamine.

  13. Methamphetamine abuse during pregnancy: outcome and fetal effects.

    PubMed

    Little, B B; Snell, L M; Gilstrap, L C

    1988-10-01

    Methamphetamines are a popular class of recreational drugs sometimes abused by women of childbearing age. The effects of methamphetamine abuse on pregnancy outcome and embryofetal development are not known. In this study, we compared pregnancy and fetal outcome in 52 women who abused methamphetamines with a randomly selected control group of 52 non-drug-abusing women. Body weight, length, and head circumference were significantly decreased in neonates born to mothers who abused methamphetamines during pregnancy. However, the frequency of congenital anomalies was not significantly increased in this group.

  14. Primary retroperitoneal mucinous cystadenocarcinoma in a male patient: a case report.

    PubMed

    Hrora, Abdelmalek; Reggoug, Sanae; Jallal, Houda; Sabbah, Farid; Benamer, Abdessalam; Alaoui, Mouna; Raiss, Mohamed; Ahallat, Mohamed

    2009-01-01

    In the literature, 51 cases of primary retroperitoneal mucinous cystadenocarcinoma have been published. We report the fourth case occurring in a male patient. The 42-year-old patient presented with multiple retroperitoneal cystic masses causing abdominal discomfort without alteration of the global clinical state. The masses were totally removed by a two-stage surgery. No other treatment has been introduced. After a follow-up of 6 months, the patient is disease-free. This rare tumor most likely arises from the mucinous metaplasia of peritoneal inclusion cysts rather than from ectopic ovarian tissue or ovarian teratomas. The occurrence of such a tumor in a male patient supports this theory. Preoperative diagnosis is mostly difficult. Clinical behavior and treatment are still controversial.

  15. 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

  16. Methamphetamine Ingestion Misdiagnosed as Centruroides sculpturatus Envenomation.

    PubMed

    Strommen, Joshua; Shirazi, Farshad

    2015-01-01

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

  17. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

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

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

    PubMed

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

    2016-01-15

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

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

    PubMed

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

    2014-03-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  1. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  4. Methamphetamine Abuse and Manufacture: The Child Welfare Response

    ERIC Educational Resources Information Center

    Hohman, Melinda; Oliver, Rhonda; Wright, Wendy

    2004-01-01

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

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

    ERIC Educational Resources Information Center

    Stanley, Jarrod M.; Lo, Celia C.

    2009-01-01

    Data from the 2005 Monitoring the Future survey were used to examine relationships between school-related factors and high school seniors' lifetime methamphetamine use. The study applied logistic regression techniques to evaluate effects of social bonding variables and social learning variables on likelihood of lifetime methamphetamine use. The…

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  7. 21 CFR 862.3610 - Methamphetamine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methamphetamine test system. 862.3610 Section 862...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems §...

  8. Neurotoxic effects of methamphetamine on rat hippocampus pyramidal neurons.

    PubMed

    Hori, N; Kadota, M T; Watanabe, M; Ito, Y; Akaike, N; Carpenter, D O

    2010-08-01

    Methamphetamine (MAP) is known to alter behavior and cause deficits in learning and memory. While the major site of action of MAP is on mesolimbic dopaminergic pathways, the effects on learning and memory raise the possibility of important actions in the hippocampus. We have studied electrophysiologic and morphologic effects of MAP in the CA1 region of hippocampus from young male rats chronically exposed to MAP, male rats exposed during gestation only and the effects of bath perfusion of MAP onto brain slices from control rats. Pyramidal neurons in brain slices from chronically exposed rats had reduced membrane potential and membrane resistance. Long-term potentiation (LTP) was reduced as compared to control, but when MAP was acutely perfused over control slices the amplitude of LTP was increased. LTP in young adult animals that had been gestationally exposed to MAP showed reduced LTP as compared to controls. Morphologically CA1 pyramidal neurons in chronically exposed animals showed a high prevalence of extensive blebbing of dendrites. We conclude that the NMDA receptor and the process of LTP are also targets of MAP dysfunction, at least in the hippocampus.

  9. Treatment of methamphetamine abuse: research findings and clinical directions.

    PubMed

    Cretzmeyer, Margaret; Sarrazin, Mary Vaughan; Huber, Diane L; Block, Robert I; Hall, James A

    2003-04-01

    Over the past few years, methamphetamine has appeared in mass quantities, in part, because of the ease and cost efficiency of manufacturing. With this increase in availability, the use of methamphetamine has increased significantly. The purpose of this article is to describe the existing treatment options for methamphetamine abuse and provide recommendations for practitioners and researchers. Methamphetamine abuse adversely impacts physical functioning, brain functioning and cognition, social support and social networks, and behavioral functioning. Negative consequences have also been documented to the environment and communities. In the studies reviewed on effective treatments, interventions consisted of aversion therapy, medication, psychosocial treatment, and case management. Each specific treatment is described as connected with an overall drug treatment program. If methamphetamine abuse continues to increase and the consequences continue to be so devastating, researchers and clinicians could advance the field by particular focus on the treatment of this type of drug use.

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

    PubMed

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

    2013-01-01

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

  11. Sexual health and stigma in urban newspaper coverage of methamphetamine.

    PubMed

    Schwartz, Joseph; Andsager, Julie L

    2008-03-01

    The epidemic use of methamphetamine in the United States is a growing public health problem. Recently its use has increased among gay men who live in urban areas, with accompanying increases in sexually transmitted diseases. This study examined how methamphetamine and sexual health are framed. It investigated the stigma associated with heterosexuals and gay men. Stories from 13 urban newspapers in cities with large populations of gay men published from 2000 to 2006 were analyzed. Results indicated that methamphetamine and sexual health were framed primarily as an individual, present problem. Stories framed methamphetamine as a health problem slightly more often than as a crime problem, but health was the dominant frame in stories mentioning gay men. Crime was the dominant frame in stories with heterosexuals. Articles tied gay men to sexual health issues. Findings indicate gay men and heterosexuals are stigmatized in news coverage of sexual issues and methamphetamine but in different ways.

  12. 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.

  13. Histamine h3 receptor antagonists potentiate methamphetamine self-administration and methamphetamine-induced accumbal dopamine release.

    PubMed

    Munzar, Patrik; Tanda, Gianluigi; Justinova, Zuzana; Goldberg, Steven R

    2004-04-01

    Methamphetamine administration increases brain levels of histamine and neuronal histamine attenuates several of methamphetamine's behavioral effects. The role of different subtypes of histamine receptors in this negative feedback, however, remains unclear. There is some evidence on possible involvement of histamine H3 receptors in these actions of methamphetamine. The aim of the present study was to evaluate the effects of two histamine H3 receptor antagonists, clobenpropit and thioperamide, on rewarding and neurochemical effects of methamphetamine utilizing three in vivo methodologies, drug self-administration, drug discrimination, and microdialysis in Sprague-Dawley rats. In rats self-administering methamphetamine intravenously under a fixed-ratio schedule, presession treatment with thioperamide (1.0-3.0 mg/kg, subcutaneous, s.c.) or clobenpropit (1.0-3.0 mg/kg, s.c.) potentiated the reinforcing effects of methamphetamine, as indicated by a dose-dependent increase in responding for a low 0.03 mg/kg dose of methamphetamine, that by itself failed to maintain responding above saline substitution levels, and a decrease in responding for a higher 0.06 mg/kg training dose of methamphetamine. In contrast, neither thioperamide nor clobenpropit treatment increased responding during saline substitution. In other rats trained to discriminate intraperitoneal (i.p.) injection of 1.0 mg/kg methamphetamine from i.p. injection of saline, both thioperamide and clobenpropit (0.3-3.0 mg/kg, s.c.) dose dependently increased methamphetamine-appropriate responding when administered with a low 0.3 mg/kg i.p. dose of methamphetamine, which by itself produced predominantly saline-appropriate responding. However, thioperamide and clobenpropit produced only saline-appropriate responding when administered with saline vehicle. Finally, thioperamide and clobenpropit potentiated methamphetamine-induced elevations in extracellular dopamine levels in the shell of the nucleus accumbens, but did

  14. Study on the THz spectrum of methamphetamine

    NASA Astrophysics Data System (ADS)

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

    2005-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Poppendieck, Dustin; Morrison, Glenn; Corsi, Richard

    2015-04-01

    Thousands of homes in the United States are found to be contaminated with methamphetamine each year. Buildings used to produce illicit methamphetamine are typically remediated by removing soft furnishings and stained materials, cleaning and sometimes encapsulating surfaces using paint. Methamphetamine that has penetrated into paint films, wood and other permanent materials can be slowly released back into the building air over time, exposing future occupants and re-contaminating furnishings. The objective of this study was to determine the efficacy of two wallboard remediation techniques for homes contaminated with methamphetamine: 1) enhancing desorption by elevating temperature and relative humidity while ventilating the interior space, and 2) painting over affected wallboard to seal the methamphetamine in place. The emission of a methamphetamine surrogate, N-isopropylbenzylamine (NIBA), from pre-dosed wallboard chambers over 20 days at 32 °C and two values of relative humidity were studied. Emission rates from wallboard after 15 days at 32 °C ranged from 35 to 1400 μg h-1 m-2. Less than 22% of the NIBA was removed from the chambers over three weeks. Results indicate that elevating temperatures during remediation and latex painting of impacted wallboard will not significantly reduce freebase methamphetamine emissions from wallboard. Raising the relative humidity from 27% to 49% increased the emission rates by a factor of 1.4. A steady-state model of a typical home using the emission rates from this study and typical residential building parameters and conditions shows that adult inhalation reference doses for methamphetamine will be reached when approximately 1 g of methamphetamine is present in the wallboard of a house.

  16. [Immunohistochemical study on the mechanism of excretion of methamphetamine].

    PubMed

    Kajitani, A; Kaiho, M; Mori, A; Okada, Y; Mukaida, M; Ishiyama, I

    1989-06-01

    Many methods of analysis are available to the forensic toxicologist for determining the amount of methamphetamine within human tissues, but few have the potential of histochemistry for enabling the precise site of excretion of methamphetamine to be defined. We have established a method for the demonstration of methamphetamine by immunohistochemistry, and applied this method for showing morphologically the disposition of methamphetamine. The following cells in the tissues of methamphetamine-intoxicated mice gave a strong positive reaction of the localization, which was thought to be the histological evidence of excretion of this drug: epithelial cells of the distal part of the renal tubule and of the collecting tubule, transitional epithelial cells of the bladder, liver parenchymal cells, epithelial cells of the striated duct of the salivary gland, parietal cells of the gastric gland, part of epithelial cells of the distal portion of the large intestine, secretory cells and part of epithelial cells of the ductal portion of the sweat gland, alveolar cells of the mammary gland, secretory cells of the sebaceous gland and hair medulla and cortex. These results indicated passive diffusion of methamphetamine across membranes of the cells of the distal tubule and collecting tubule of the kidney, of the bladder and of the striated duct of the salivary gland. In the parietal cells of the gastric gland, part of epithelial cells of the distal portion of the large intestine and secretory cells of the sweat gland, methamphetamine was thought to be stored and subsequently released. In the mammary gland, methamphetamine was found to be combined with casein and excreted by exocytosis. Accumulation of methamphetamine in the hair was supposed to be chiefly due to the penetration of this drug derived from tissue fluid and sebum.

  17. Glutamatergic Neurometabolites during Early Abstinence from Chronic Methamphetamine Abuse

    PubMed Central

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

    2015-01-01

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

  18. Decreased frontal lobe phosphocreatine levels in methamphetamine users

    PubMed Central

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

    2012-01-01

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

  19. [Vibration studies of amphetamine and methamphetamine by micro Raman].

    PubMed

    Zhao, J; Chen, D; Zhang, P; Lu, F; Xie, H; Li, H

    1999-10-01

    For the first time, we obtained and investigated the Raman spectra of amphetamine and methamphetamine by micro Raman with incidence excitation light 514.5 nm under the ambient environment. According to the fact that both molecules belong to single substituted benzene which has the symmetry of Cy2v, the attribution of Raman vibration modes in amphetamine and methamphetamine molecules was carried out by studying the spectral lines in the two spectra. The Raman line that only appeared in methamphetamine but could not be seen in any other drugs we have investigated was most possibly attributed to the stretching vibration between C-N(+)-C.

  20. Common experience modifies the reinforcing properties of methamphetamine-injected cage mates but not morphine-injected cage mates in C57 mice.

    PubMed

    Watanabe, Shigeru

    2015-10-01

    The aim of this study was to determine whether previous exposure to a drug affects the social facilitation of conditioned place preference (CPP) for a drug-injected cage mate. Twenty-two male C57/BL6J mice received drug injections (methamphetamine or morphine) and 22 male C57/BL6J mice received saline injections. All 44 mice then received CPP training, during which one compartment of a conventional CPP apparatus was associated with a drug-injected cage mate (stimulus mouse) and the other compartment was associated with a saline-injected cage mate (stimulus mouse). The subject mice did not receive any drug injection during this CPP training. Time spent in the compartment associated with the drug-injected cage mate was measured before and after training. Subject mice that had previously received methamphetamine injections showed an increase in the time spent in the compartment associated with the methamphetamine-injected cage mate after CPP training. This effect was not observed in subject mice that had previously received saline injections. Subject mice did not show an increase in the time spent in the compartment associated with the morphine-injected cage mate irrespective of whether they had previously received morphine or saline injections. Therefore, in agreement with previous reports, common experience with methamphetamine induced reinforcing properties, but that with morphine did not.

  1. Elevated Plasma Prolactin in Abstinent Methamphetamine-Dependent Subjects

    PubMed Central

    Zorick, Todd; Mandelkern, Mark A.; Lee, Buyean; Wong, Ma-Li; Miotto, Karen; Shabazian, Jon; London, Edythe D.

    2011-01-01

    Background Methamphetamine use disorders are pervasive global social problems that produce large medical and public health burdens. Abnormalities in pituitary hormonal regulation have been observed in preclinical models of substance abuse and in human substance abusers. They have not been studied before, however, in methamphetamine-dependent human subjects. Objectives To determine if methamphetamine-dependent research volunteers differ from healthy control subjects in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, or prolactin, or in pituitary dopamine D2 receptor availability during early abstinence from methamphetamine. Methods Methamphetamine-dependent subjects (N=31), who were not seeking treatment, resided on an inpatient ward for up to 5 weeks. Abstinence was confirmed by daily urine drug screening. Venous blood was sampled for plasma hormone levels, and positron emission tomography with [18F]fallypride was performed to determine dopamine D2 receptor availability during the first week of abstinence. Venous blood was sampled again for hormone levels during the fourth week of abstinence. Matched healthy volunteers (N=23) participated as a comparison group. Results Methamphetamine-dependent and healthy comparison subjects did not differ in plasma ACTH or cortisol levels, but had an elevated plasma prolactin at both the first week and fourth week of abstinence. There was no group difference in pituitary dopamine D2 receptor availability. Conclusion Methamphetamine-dependent individuals have abnormalities in prolactin regulation, which is not likely due to alterations in pituitary dopamine D2 receptor availability. Scientific Significance Methamphetamine dependence is associated with elevated prolactin levels, which may contribute to medical co-morbidity in afflicted individuals. PMID:21142706

  2. Syphilis and methamphetamine use among female sex workers in Shandong Province, China.

    PubMed

    Liao, Meizhen; Jiang, Zhenxia; Zhang, Xijiang; Kang, Dianming; Bi, Zhenqiang; Liu, Xuezhen; Fu, Jihua; Zhang, Ning; Mao, Wenwen; Jiang, Baofa; Jia, Yujiang

    2011-01-01

    A study of female sex workers in China, found alarmingly high prevalence of methamphetamine use. Methamphetamine users were more likely to be single, younger, inconsistent condom users, and have syphilis.

  3. Impact of methamphetamine on infection and immunity.

    PubMed

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

    2014-01-01

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

  4. METHAMPHETAMINE TOXICITY AND MESSENGERS OF DEATH

    PubMed Central

    Krasnova, Irina N.; Cadet, Jean Lud

    2009-01-01

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

  5. Impact of methamphetamine on infection and immunity

    PubMed Central

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

    2015-01-01

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

  6. GABAergic mRNA expression is upregulated in the prefrontal cortex of rats sensitized to methamphetamine.

    PubMed

    Wearne, Travis A; Parker, Lindsay M; Franklin, Jane L; Goodchild, Ann K; Cornish, Jennifer L

    2016-01-15

    Inhibitory gamma-aminobutyric acid (GABA)-mediated neurotransmission plays an important role in the regulation of the prefrontal cortex (PFC), with increasing evidence suggesting that dysfunctional GABAergic processing of the PFC may underlie certain deficits reported across psychotic disorders. Methamphetamine (METH) is a psychostimulant that induces chronic psychosis in a subset of users, with repeat administration producing a progressively increased vulnerability to psychotic relapse following subsequent drug administration (sensitization). The aim here was to investigate changes to GABAergic mRNA expression in the PFC of rats sensitized to METH using quantitative polymerase chain reaction (qPCR). Male Sprague-Dawley rats (n=12) underwent repeated methamphetamine (intraperitoneal (i.p.) or saline injections for 7 days. Following 14 days of withdrawal, rats were challenged with acute methamphetamine (1mg/kg i.p.) and RNA was isolated from the PFC to compare the relative mRNA expression of a range of GABA enzymes, transporters and receptors subunits. METH challenge resulted in a significant sensitized behavioral (locomotor) response in METH pre-treated animals compared with saline pre-treated controls. The mRNAs of transporters (GAT1 and GAT3), ionotropic GABAA receptor subunits (α3 and β1), together with the metabotropic GABAB1 receptor, were upregulated in the PFC of sensitized rats compared with saline controls. These findings indicate that GABAergic mRNA expression is significantly altered at the pre and postsynaptic level following sensitization to METH, with sensitization resulting in the transcriptional upregulation of several inhibitory genes. These changes likely have significant consequences on GABA-mediated neurotransmission in the PFC and may underlie certain symptoms conserved across psychotic disorders, such as executive dysfunction.

  7. 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.

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

    PubMed

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

    2012-01-01

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

  9. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  10. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    ERIC Educational Resources Information Center

    Lamonica, Aukje K.; Boeri, Miriam

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Connell-Carrick, Kelli

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-01

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

  17. The neuronal nitric oxide synthase inhibitor, 7-nitroindazole, protects against methamphetamine-induced neurotoxicity in vivo.

    PubMed

    Itzhak, Y; Ali, S F

    1996-10-01

    The present study was undertaken to investigate whether the relatively selective neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against methamphetamine (METH)-induced neurotoxicity. Male Swiss Webster mice received the following treatments (i.p.; q 3 h x 3): (a) vehicle/saline, (b) 7-NI (25 mg/kg)/saline, (c) vehicle/METH (5 mg/kg), and (d) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (a) and (b) received two vehicle injections, and groups (c) and (d) received two 7-NI injections (25 mg/kg, each). Administration of vehicle/METH resulted in 68, 44, and 55% decreases in the concentration of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, respectively, and a 48% decrease in the number of [3H]mazindol binding sites in the striatum compared with control values. Treatment with 7-NI (group d) provided full protection against the depletion of dopamine and its metabolites and the loss of dopamine transporter binding sites. Administration of 7-NI/saline (group b) affected neither the tissue concentration of dopamine and its metabolites nor the binding parameters of [3H] mazindol compared with control values. 7-NI had no significant effect on animals' body temperature, and it did not affect METH-induced hyperthermia. These findings indicate a role for nitric oxide in methamphetamine-induced neurotoxicity and also suggest that blockade of NOS may be beneficial for the management of Parkinson's disease.

  18. Methamphetamine-induced locomotor activity and behavioral sensitization: are dopamine d3 receptors involved?

    PubMed

    Jones, C D; Bartee, J A; Leite-Browning, M L; Blackshear, M A

    2007-05-15

    Drug sensitization is a behavioral phenomenon that occurs following repeated administration of methamphetamine (METH) and similar CNS stimulants. The mechanism of drug sensitization is unknown, but is believed to be due to downregulation of dopamine D3 receptors. It is hypothesized that repeated administration of dopamine D3 agonists results in downregulation of D3 receptors in methamphetamine-induced (METH-IND) sensitization. Furthermore, repeated administration of dopamine D3 antagonists and METH cause upregulation of D3 receptors and block METH-IND sensitization. The objective of this study was to determine the role of D3 receptors in METH-IND sensitization. To test these hypotheses, male mice received chronic injections (i.p.) of 2 mg/kg of the dopamine D3 agonist, PD128907 plus 0.5 mg/kg of METH or 8 mg/kg of D3 antagonist, U99194A and 0.5 mg\\kg of METH daily for 7-days. Drugs were withdrawn on day 8, and METH-IND sensitization was determined on day 18. Locomotor activity was measured for 75 minutes immediately after METH administration in an activity monitor. Acute administration of PD128907 decreased METH-IND locomotion, p < 0. 01, and acute U99194A increased it. However, chronic administration of these drugs did not alter the locomotor effects of METH (p > 0.05). These findings support in-part the hypothesis that dopamine D3 receptors are downregulated in METH-IND sensitization.

  19. Effect of postnatal methamphetamine trauma and adolescent methylphenidate treatment on adult hippocampal neurogenesis in gerbils.

    PubMed

    Schaefers, Andrea T; Teuchert-Noodt, Gertraud; Bagorda, Francesco; Brummelte, Susanne

    2009-08-15

    Methylphenidate (e.g. Ritalin) is the most common drug used in the treatment of attention-deficit hyperactivity disorder. However, only a few studies have investigated the neuroanatomical long-term effects of this treatment. Prolonged application of methylphenidate during adolescence causes alterations in dopaminergic fiber or receptor densities in adult rodents. This study was conducted to investigate the effects of adolescent methylphenidate treatment on adult hippocampal neurogenesis in male gerbils (Meriones unguiculatus). Animals were first treated with either a single methamphetamine challenge on postnatal day 14 (to cause a disturbance in the dopaminergic system, to mimic the disturbed dopaminergic system seen in ADHD children) or saline and then received a daily oral application of 5 mg/kg methylphenidate or water from postnatal day 30-60 or were left undisturbed. On postnatal 90 gerbils were injected with bromodeoxyuridine (BrdU, a DNA synthesis marker) and sacrificed seven days later. Results reveal that the pretreatment with methamphetamine causes a decrease in the number of BrdU-positive cells in the dentate gyrus. Methylphenidate treatment however did not cause any differences in the number of labelled cells in any group. This implies that, despite methylphenidate's efficiency in inducing changes in the dopaminergic system and associated areas, it might be less effective in altering neurogenesis in the hippocampus.

  20. Potentiating effect of morphine upon d-methamphetamine-induced hyperthermia in mice. Effects of naloxone and haloperidol.

    PubMed

    Funahashi, M; Kohda, H; Hori, O; Hayashida, H; Kimura, H

    1990-06-01

    We have examined changes in rectal temperature of mice after subcutaneous administrations of d-methamphetamine alone or methamphetamine plus morphine. Methamphetamine 5 mg/kg produced slight hyperthermia, while simultaneous administration of morphine (25-100 mg/kg), which alone produces hypothermia, potentiated markedly the increase in body temperature by methamphetamine. Methamphetamine showed a hyperthermic effect in a dose-dependent manner in the presence of morphine. The hyperthermia due to methamphetamine plus morphine was avoided by pretreatment with 10 mg/kg naloxone. When animals were pretreated with 2.5 mg/kg haloperidol, hyperthermia due to methamphetamine alone was completely abolished, while that due to methamphetamine plus morphine was still observed. These results showed that dopamine may be implicated in methamphetamine hyperthermia and a haloperidol-nonsensitive mechanism may be involved in the methamphetamine-morphine hyperthermia.

  1. Segmental hair analysis and estimation of methamphetamine use pattern.

    PubMed

    Han, Eunyoung; Yang, Heejin; Seol, Ilung; Park, Yunshin; Lee, Bongwoo; Song, Joon Myong

    2013-03-01

    The aim of this study was to investigate whether the results of segmental hair analysis can be used to estimate patterns of methamphetamine (MA) use. Segmental hair analysis for MA and amphetamine (AP) was performed. Hair was cut into the hair root, consecutive 1 cm length segments and 1-4 cm length segments. Whole hair was also analyzed. The hair samples were incubated for 20 h in 1 mL methanol containing 1 % hydrochloric acid after washing the hair samples. Hair extracts were evaporated and derivatization was performed using trifluoroacetic anhydride in ethylacetate at 65 °C for 30 min. Derivatized extract was analyzed by gas chromatography/mass spectrometry. The 15 subjects consisted of 13 males and two females and their ages ranged from 25 to 42 (mean, 32). MA and AP concentrations in the whole hair ranged from 3.00 to 105.10 ng/mg (mean, 34.53) and from 0.05 to 4.76 ng/mg (mean, 2.42), respectively. Based on the analysis of the 1 cm length segmental hair, the results were interpreted in a way to distinguish between continuous use of MA (n = 10), no recent but previous use of MA (n = 3), and recent but no previous use of MA (n = 2). Furthermore, the individuals were interpreted as light, moderate, and heavy users based on concentration ranges previously published.

  2. Role of adenosine receptor subtypes in methamphetamine reward and reinforcement.

    PubMed

    Kavanagh, Kevin A; Schreiner, Drew C; Levis, Sophia C; O'Neill, Casey E; Bachtell, Ryan K

    2015-02-01

    The neurobiology of methamphetamine (MA) remains largely unknown despite its high abuse liability. The present series of studies explored the role of adenosine receptors on MA reward and reinforcement and identified alterations in the expression of adenosine receptors in dopamine terminal areas following MA administration in rats. We tested whether stimulating adenosine A1 or A2A receptor subtypes would influence MA-induced place preference or MA self-administration on fixed and progressive ratio schedules in male Sprague-Dawley rats. Stimulation of either adenosine A1 or A2A receptors significantly reduced the development of MA-induced place preference. Stimulating adenosine A1, but not A2A, receptors reduced MA self-administration responding. We next tested whether repeated experimenter-delivered MA administration would alter the expression of adenosine receptors in the striatal areas using immunoblotting. We observed no change in the expression of adenosine receptors. Lastly, rats were trained to self-administer MA or saline for 14 days and we detected changes in adenosine A1 and A2A receptor expression using immunoblotting. MA self-administration significantly increased adenosine A1 in the nucleus accumbens shell, caudate-putamen and prefrontal cortex. MA self-administration significantly decreased adenosine A2A receptor expression in the nucleus accumbens shell, but increased A2A receptor expression in the amygdala. These findings demonstrate that MA self-administration produces selective alterations in adenosine receptor expression in the nucleus accumbens shell and that stimulation of adenosine receptors reduces several behavioral indices of MA addiction. Together, these studies shed light onto the neurobiological alterations incurred through chronic MA use that may aid in the development of treatments for MA addiction.

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2013-10-01

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

  5. 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.

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

    Turowski, Patric; Kenny, Bridget-Ann

    2015-01-01

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

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

    PubMed

    Turowski, Patric; Kenny, Bridget-Ann

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

  10. METHAMPHETAMINE USE AMONG RURAL WHITE AND NATIVE AMERICAN ADOLESCENTS: AN APPLICATION OF THE STRESS PROCESS MODEL

    PubMed Central

    Eitle, David J.; McNulty Eitle, Tamela

    2016-01-01

    Methamphetamine use has been identified as having significant adverse health consequences, yet we know little about the correlates of its use. Additionally, research has found that Native Americans are at the highest risk for methamphetamine use. Our exploratory study, informed by the stress process model, examines stress and stress buffering factors associated with methamphetamine use among a cross-sectional sample of rural white and Native American adolescents (n=573). Results of logistic regression analyses revealed mixed support for the stress process model; while stress exposure and family methamphetamine use predicted past year methamphetamine use, the inclusion of these variables failed to attenuate the association between race and past year use. PMID:25445505

  11. Childhood histories of attention-deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: preliminary report.

    PubMed

    Matsumoto, Toshihiko; Kamijo, Atsushi; Yamaguchi, Akiko; Iseki, Eizo; Hirayasu, Yoshio

    2005-02-01

    The present study examined childhood histories of attention-deficit hyperactivity disorder (ADHD) in 54 methamphetamine and 12 inhalant abusers using the Wender Utah Rating Scale. The inhalant abusers experienced initial drinking at a younger age than methamphetamine abusers (P=0.038). The Wender Utah Rating Scale score was significantly higher in the inhalant abusers than in the methamphetamine abusers (P=0.013) although 83.3% of inhalant and 55.6% of methamphetamine abusers had higher scores than the cut-off for ADHD. These findings suggest that drug abuse is associated with childhood ADHD, and that inhalant abusers have a higher incidence of childhood ADHD than methamphetamine abusers.

  12. Urinary pharmacokinetics of methamphetamine and its metabolite, amphetamine following controlled oral administration to humans.

    PubMed

    Kim, Insook; Oyler, Jonathan M; Moolchan, Eric T; Cone, Edward J; Huestis, Marilyn A

    2004-12-01

    Methamphetamine is widely abused for its euphoric effects. Our objectives were to characterize the urinary pharmacokinetics of methamphetamine and amphetamine after controlled methamphetamine administration to humans and to improve the interpretation of urine drug test results. Participants (n = 8) received 4 daily 10-mg (low) oral doses of sustained-release (d)-methamphetamine hydrochloride within 7 days. After 4 weeks, 5 participants received 4 daily 20-mg (high) oral doses. All urine specimens were collected during the study. Methamphetamine and amphetamine were measured by GC-MS/PCI. Maximum excretion rates ranged from 403 to 4919 microg/h for methamphetamine and 59 to 735 microg/h for amphetamine with no relationship between dose and excretion rate. The mean molar percentage of dose in the urine as total methamphetamine and amphetamine were 57.5 +/- 21.7% (low dose) and 40.9 +/- 8.5% (high dose). Mean urinary terminal elimination half-lives across doses were 23.6 +/- 6.6 hours for methamphetamine and 20.7 +/- 7.3 hours for amphetamine. Methamphetamine renal clearance across doses was 175 +/- 102 mL/min. The mean amphetamine/methamphetamine percentage ratio based on the area under the urinary excretion-time curve increased over time from 13.4 +/- 6.5% to 35.7 +/- 26.6%. Slow urinary excretion results in drug accumulation and increases in detection time windows. Our findings also support the presence of an active renal excretion mechanism for methamphetamine.

  13. 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.

  14. The cardiovascular and subjective effects of methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers.

    PubMed

    De La Garza, Richard; Zorick, Todd; Heinzerling, Keith G; Nusinowitz, Steve; London, Edythe D; Shoptaw, Steven; Moody, David E; Newton, Thomas F

    2009-11-01

    Gamma-vinyl-gamma-aminobutyric acid (GVG) elevates central nervous system gamma-aminobutyric acid (GABA) levels by irreversibly inhibiting GABA transaminase. An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use. To test safety and to obtain preliminary data on efficacy of GVG for treating methamphetamine dependence, we conducted a double-blind, placebo-controlled, parallel group study of GVG interaction with the cardiovascular and subjective effects produced by methamphetamine. Non-treatment seeking methamphetamine-dependent volunteers received either GVG (N=8) or placebo (N=9) by random assignment. GVG treatment was initiated at 1 g/day and increased to 5 g/day. After reaching the target dose of 5 g/day, participants received methamphetamine (15+30 mg, IV), and cardiovascular and subjective effects were assessed. No serious adverse events were noted, and the total number of adverse events was similar between the treatment groups. Considering the full time course and peak effects independently, no significant differences were detected between the groups for systolic or diastolic blood pressures, or heart rate, following methamphetamine exposure. Some methamphetamine-induced cardiovascular changes approached significance (p<0.10) and may warrant attention in future trials. Methamphetamine-induced subjective effects ("any drug effect", "high", "crave methamphetamine") were statistically similar between GVG and placebo treatment groups. Pharmacokinetic data indicate that GVG treatment did not alter methamphetamine or amphetamine plasma levels, and there was no association between methamphetamine or amphetamine plasma levels and peak cardiovascular effects. Taken together, the data indicate that GVG treatment is generally well tolerated but not efficacious in attenuating the positive subjective effects of methamphetamine in the laboratory.

  15. 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

  16. The role of dopamine receptors in the neurotoxicity of methamphetamine.

    PubMed

    Ares-Santos, S; Granado, N; Moratalla, R

    2013-05-01

    Methamphetamine is a synthetic drug consumed by millions of users despite its neurotoxic effects in the brain, leading to loss of dopaminergic fibres and cell bodies. Moreover, clinical reports suggest that methamphetamine abusers are predisposed to Parkinson's disease. Therefore, it is important to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity. Dopamine receptors may be a plausible target to prevent this neurotoxicity. Genetic inactivation of dopamine D1 or D2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D1 receptor inactivation is due to blockade of hypothermia, reduced dopamine content and turnover and increased stored vesicular dopamine in D1R(-/-) mice. However, the neuroprotective impact of D2 receptor inactivation is partially dependent on an effect on body temperature, as well as on the blockade of dopamine reuptake by decreased dopamine transporter activity, which results in reduced intracytosolic dopamine levels in D2R(-/-) mice.

  17. A Qualitative Exploration of Trajectories Among Suburban Users of Methamphetamine

    PubMed Central

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

    2009-01-01

    The goal of this exploratory study was to gain a better understanding of methamphetamine use among suburban users. We know very little about the mechanisms of initiation and trajectory patterns of methamphetamine use among this under-researched and hidden population. This study employed qualitative methods to examine the drug career of suburban methamphetamine users. Analysis of in-depth interviews with 48 former and current users indicated that suburban users often initiate and continue use for functional purposes. Turning points into dysfunctional use included loss of work, broken relationships, and stress related to a suburban lifestyle. The route to cessation included frequent relapses. Findings call for treatment and prevention programs targeted for specific patterns of suburban use. PMID:21552386

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

    PubMed Central

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

    2013-01-01

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

  19. Role for Rab10 in Methamphetamine-Induced Behavior.

    PubMed

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

    2015-01-01

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

  20. Role for Rab10 in Methamphetamine-Induced Behavior

    PubMed Central

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

    2015-01-01

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

  1. Prenatal Methamphetamine Use and Neonatal Neurobehavioral Outcome

    PubMed Central

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

    2008-01-01

    Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How prenatal MA exposure affects neonatal neurobehavior is unknown. Objective To examine the neurobehavioral effects of prenatal MA exposure. Design The Infant Development, Environment and Lifestyle (IDEAL) study screened 13,808 subjects and 1632 were eligible and consented. 166 (n=74 exposed) were enrolled in a longitudinal follow up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose-response relationships with amphetamine metabolites. Results After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated physiological stress. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. Conclusions Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose response relationships may represent neurotoxic effects from MA. PMID:18031987

  2. The Methamphetamine Problem in the United States

    PubMed Central

    Gonzales, Rachel; Mooney, Larissa; Rawson, Richard

    2015-01-01

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

  3. Violence perpetrated by women who use methamphetamine

    PubMed Central

    HAMILTON, ALISON B.; GOEDERS, NICHOLAS E.

    2015-01-01

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

  4. Chronic methamphetamine increases fighting in mice.

    PubMed

    Sokolov, Boris P; Schindler, Charles W; Cadet, Jean Lud

    2004-02-01

    A propensity for violent behaviors to develop in chronic methamphetamine (METH) abusers has been noted. The idea that increased aggressiveness might result from chronic METH administration was tested in mice after chronic (long-term intermittent, 8 weeks) or single exposures to the drug. A single injection of METH (6 mg/kg) did not augment fighting. In contrast, chronic METH administration significantly increased the number of animals that initiated bite attacks. This regimen also shortened the latency before the first attack. Latency before the first attack was shorter at 20 h after the METH injection than at 15 min after injection. Locomotor activity was not different at 20 h after METH injection, indicating that increased fighting was not secondary to METH-induced hyperactivity. METH-induced increases in fighting were not related to the duration of persistent sniffing after the initial encounter with an intruder since the duration of this behavior was significantly increased at 15 min after METH but not at 20 h post drug. These results indicate that repeated injections of METH can increase fighting behaviors and also alter social interactions in mice. Thus, intermittent administration of METH might be useful as a pharmacological model to study the biochemical and molecular bases of aggressiveness.

  5. Histochemical demonstration of methamphetamine by immunocytochemistry.

    PubMed

    Ishiyama, I; Mukaida, M; Yoshii, T; Suyama, H

    1987-05-01

    A method for the demonstration of methamphetamine (MA) by immunocytochemistry was established. The tissues of intoxicated mice, administered various amounts of MA in single doses of from 0.01 to 1 mg of MA-HCl, were fixed in glutaraldehyde-containing fixatives. Cryostat and paraffin slices gave a positive reaction of MA localization by staining the brain, liver, kidney, lung, stomach, spleen, and so forth, with the aid of the indirect immunoperoxidase technique. Those of animals administered a single dose of 0.1 mg or more (over 3 to 4 mg/kg--the usual dose of MA in acute intoxication death in forensic medicine), in particular, gave a strong strong reaction, so that the diagnosis of MA intoxication can be performed by macroscopic observation of stained slices. The histochemical diagnosis of MA intoxication in clinical toxicology and pathology might be regarded as a useful tool, especially in forensic pathology. The following cells gave a strong positive reaction: nerve cells and myelin sheaths, hepatocytes, epithelial cells of the distal part of the renal tubule and of the collecting tubule, alveolar and bronchial epithelial cells of the lung, chief and parietal cells of the gastric gland, capillaries of the renal glomerulus, macrophages in the blood and tissues, and striated muscle cells including cardiocytes. The morphological evidence of the pharmacodynamics and pharmacokinetics of MA can be determined at the cellular level by immunocytochemistry.

  6. 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

  7. 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

  8. Methamphetamines: use and trafficking in the Tucson-Nogales area.

    PubMed

    Glittenberg, J; Anderson, C

    1999-12-01

    A national increase in the use of methamphetamine, a cheap, accessible, and dangerous drug, prompted the National Institute on Drug Addiction to sponsor an ethnographic study in the Tucson-Nogales area. This area has experienced a rapid rise in methamphetamine (also known as meth, speed, crank, smoke, or crystal ice) use during the past 3 years. Mexican and Canadian borders are ports of entry for meth and precursor substances, and home manufacturing has increased substantially. The dual consequences of overdose and addiction result in devastating long-term psychological and physiological problems. Increased law enforcement and citizen awareness in controlling the "epidemic" are key elements in curbing the problem.

  9. Bullous Skin Lesions in an Adult Male: A Diagnostic Dilemma

    PubMed Central

    Gulati, Gaurav; Siv, Jenny; Ware, Avis E.

    2015-01-01

    Patient: Male, 42 Final Diagnosis: Henoch-Schönlein Purpura (HSP) Symptoms: Bullous hemorrhagic lesions • elevated liver enzymes Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Unusual clinical course Background: Henoch-Schönlein Purpura (HSP) is an IgA small-vessel vasculitis that is primarily a disease of childhood. Its presentation in adulthood is rare and has a more severe disease course. We present a case with an atypical presentation of this disease that was a diagnostic challenge for multiple providers. Case Report: A 42-year-old man noticed bullous lesions over his ankles that spread to his entire legs over a few weeks. They later became necrotic and ulcerated areas. His primary care physician and 2 dermatologists could not reach a definitive diagnosis. He then presented to our hospital with new abdominal pain, rectal bleeding, and a new elevation in liver enzymes. A biopsy of his skin lesions led to the diagnosis of HSP. Conclusions: We discuss this highly unusual initial presentation with bullous skin lesions and liver enzyme abnormalities and explore the medical literature to understand its pathogenesis. Clinicians need to be aware of this rare presentation to avoid a delay in diagnosis and management. PMID:25858335

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

    PubMed

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

    2010-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Leech, Ronald; Stark, Jeffrey G.

    2013-01-01

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

  13. 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.

  14. [The clinical course of chronic methamphetamine psychoses].

    PubMed

    Fujimori, H; Nakatani, Y; Sakaguchi, M

    1989-09-01

    3 cases with chronic methamphetamine psychoses (MAP-P) were studied from the clinical psychiatric point of view and discussed: 1.) The average time of occurrence of psychotic symptoms in our 3 cases after beginning of MAP abuse was two or three years. 2.) Although the psychotic states (often schizophrenia-like) were stable for a short time, the symptoms recurred promptly after reinjection of a small amount of MAP, unspecific stress or drinking sake (flashback phenomenon). The recurrence may happen even after several years. 3.) In cases of chronic MAP-P disturbances of consciousness are rare. Chronic process of MAP-P cases may show acute transient disturbances of consciousness (flashback phenomenon). 4.) The change of affects and behaviour ranges between irritable and indifferent attitudes. While there are close connections between the disturbance of feeling and change of personality (Wesensänderung), it is very difficult to decide whether premorbid character traits are dominant or there is a change of personality or emotional disturbance. 5.) About acute psychic symptoms which are responsible for recurrence of MAP-P, MAP-abusers make the experience that their intimate personal affairs are overlooked and become public (uncovered defensive experiences). In chronic cases of MAP-P we often meet patients with hypertrophic self-feeling or delusion of grandeur predominant in the symptomatology. 6.) In our cases sensations were amalgamated into each other and there were hallucinatory experiences without clear division between them. 7.) In chronic cases the auditory hallucinations criticized or censured the patients for their behaviour. Thought echoing (Gedankenlautwerden) was found. We found signs of mind reading (Gedankenausbreitung).

  15. Nucleus accumbens invulnerability to methamphetamine neurotoxicity.

    PubMed

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

    2011-01-01

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

  16. Methamphetamine reduces human influenza A virus replication.

    PubMed

    Chen, Yun-Hsiang; Wu, Kuang-Lun; Chen, Chia-Hsiang

    2012-01-01

    Methamphetamine (meth) is a highly addictive psychostimulant that is among the most widely abused illicit drugs, with an estimated over 35 million users in the world. Several lines of evidence suggest that chronic meth abuse is a major factor for increased risk of infections with human immunodeficiency virus and possibly other pathogens, due to its immunosuppressive property. Influenza A virus infections frequently cause epidemics and pandemics of respiratory diseases among human populations. However, little is known about whether meth has the ability to enhance influenza A virus replication, thus increasing severity of influenza illness in meth abusers. Herein, we investigated the effects of meth on influenza A virus replication in human lung epithelial A549 cells. The cells were exposed to meth and infected with human influenza A/WSN/33 (H1N1) virus. The viral progenies were titrated by plaque assays, and the expression of viral proteins and cellular proteins involved in interferon responses was examined by Western blotting and immunofluorescence staining. We report the first evidence that meth significantly reduces, rather than increases, virus propagation and the susceptibility to influenza infection in the human lung epithelial cell line, consistent with a decrease in viral protein synthesis. These effects were apparently not caused by meth's effects on enhancing virus-induced interferon responses in the host cells, reducing viral biological activities, or reducing cell viability. Our results suggest that meth might not be a great risk factor for influenza A virus infection among meth abusers. Although the underlying mechanism responsible for the action of meth on attenuating virus replication requires further investigation, these findings prompt the study to examine whether other structurally similar compounds could be used as anti-influenza agents.

  17. Methamphetamine-induced hyperthermia and lethal toxicity: role of the dopamine and serotonin transporters.

    PubMed

    Numachi, Yohtaro; Ohara, Arihisa; Yamashita, Motoyasu; Fukushima, Setsu; Kobayashi, Hideaki; Hata, Harumi; Watanabe, Hidekazu; Hall, F Scott; Lesch, Klaus-Peter; Murphy, Dennis L; Uhl, George R; Sora, Ichiro

    2007-10-31

    We examined the hyperthermic and lethal toxic effects of methamphetamine in dopamine transporter (DAT) and/or serotonin transporter (SERT) knockout (KO) mice. Methamphetamine (45 mg/kg) caused significant hyperthermia even in the mice with a single DAT gene copy and no SERT copies (DAT+/- SERT-/- mice). Mice with no DAT copies and a single SERT gene copy (DAT-/- SERT+/- mice) showed significant but reduced hyperthermia when compared to wild-type mice after methamphetamine. Surprisingly, DAT/SERT double KO mice exhibited a paradoxical hypothermia after methamphetamine. These results demonstrate that methamphetamine exerts a hyperthermic effect via DAT, or via SERT, in the absence of DAT. The selective norepinephrine transporter blocker (20 mg/kg nisoxetine) caused hyperthermia in DAT/SERT double KO mice, suggesting that the norepinephrine system is not responsible for methamphetamine-induced paradoxical hypothermia in the double KO mice. DAT gene deletion in mice strikingly increased LD50 of methamphetamine by 1.7-1.8 times that of wild-type mice, suggesting that the lethal toxic effect of methamphetamine is mainly dependent on DAT. Moreover, dissociation between hyperthermic and lethal toxic effects of methamphetamine in DAT single KO mice and DAT/SERT double KO mice suggest that hyperthermia is not a prerequisite for methamphetamine-induced lethality. Methamphetamine (45 mg/kg) significantly increased mRNA of interleukin-1beta, which is the major endogenous pyrogen, in the hypothalamus of wild-type mice but not in DAT/SERT double KO mice, which provides a partial mechanism of methamphetamine-induced paradoxical hypothermia. These results suggest that DAT and SERT are key molecules for hyperthermic and lethal toxic effects of methamphetamine.

  18. Morphine intake and the effects of naltrexone and buprenorphine on the acquisition of methamphetamine intake.

    PubMed

    Eastwood, E C; Phillips, T J

    2014-02-01

    Some common genetic factors appear to influence risk for drug dependence across multiple drugs of abuse. In previous research, mice that were selectively bred for higher amounts of methamphetamine consumption, using a two-bottle choice methamphetamine drinking procedure, were found to be less sensitive to the locomotor stimulant effects of morphine and of the more selective μ-opioid receptor agonist fentanyl, compared to mice that were bred for low methamphetamine consumption. This suggested that μ-opioid receptor-mediated pathways may influence genetic risk for methamphetamine consumption. We hypothesized that these differences in opioid sensitivity would impact opioid intake in the methamphetamine drinking lines and that drugs with μ-opioid receptor activity would impact methamphetamine intake. Consumption of morphine was examined in 2, two-bottle choice studies, one that compared morphine to quinine consumption and another that used a saccharin fading procedure. Next, naltrexone (0, 0.5, 1, 2, 5, 10 and 20 mg/kg), a μ-opioid receptor antagonist, and buprenorphine (0, 1, 2 or 4 mg/kg), a μ-opioid receptor partial agonist, were each examined for their effects on the acquisition of methamphetamine consumption. Low methamphetamine drinking mice consumed more morphine compared to high methamphetamine drinking mice. Naltrexone did not alter methamphetamine consumption in either selected line; however, buprenorphine reduced methamphetamine intake in the high methamphetamine drinking line. These data show that greater sensitivity to opioids is associated with greater opioid intake and warrant further investigation of drugs with μ-opioid receptor-specific agonist activity in genetically determined differences in methamphetamine consumption.

  19. PG01037, a novel dopamine D3 receptor antagonist, inhibits the effects of methamphetamine in rats.

    PubMed

    Higley, Amanda E; Spiller, Krista; Grundt, Peter; Newman, Amy Hauck; Kiefer, Stephen W; Xi, Zheng-Xiong; Gardner, Eliot L

    2011-02-01

    Our previous studies have shown that the selective dopamine D(3) receptor antagonists SB-277011A or NGB 2904 significantly attenuate cocaine self-administration under a progressive-ratio reinforcement schedule and cocaine-, methamphetamine- or nicotine-enhanced brain stimulation reward. However, the poor bioavailability of SB-277011A has limited its potential use in humans. In the present study, we investigated the effects of the novel D(3) receptor antagonist PG01037 on methamphetamine self-administration, methamphetamine-associated cue-induced reinstatement of drug seeking and methamphetamine-enhanced brain stimulation reward. Rats were allowed to intravenously self-administer methamphetamine under fixed-ratio 2 and progressive-ratio reinforcement conditions, and then the effects of PG01037 on methamphetamine self-administration and cue-induced reinstatement were assessed. Additional groups of rats were trained for intracranial electrical brain stimulation reward and the effects of PG01037 and methamphetamine on brain stimulation reward were assessed. Acute intraperitoneal administration of PG01037 (3, 10, 30 mg/kg) failed to alter methamphetamine or sucrose self-administration under fixed-ratio 2 reinforcement, but significantly lowered the break-point levels for methamphetamine or sucrose self-administration under progressive-ratio reinforcement. In addition, PG01037 significantly inhibited methamphetamine-associated cue-triggered reinstatement of drug-seeking behavior and methamphetamine-enhanced brain stimulation reward. These data suggest that the novel D(3) antagonist PG01037 significantly attenuates the rewarding effects as assessed by progressive-ratio self-administration and brain stimulation reward, and inhibits methamphetamine-associated cue-induced reinstatement of drug-seeking behavior These findings support the potential use of PG01037 or other selective D(3) antagonists in the treatment of methamphetamine addiction.

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

    PubMed Central

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

    2015-01-01

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

  1. The central amygdala nucleus is critical for incubation of methamphetamine craving.

    PubMed

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

    2015-04-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  3. [Treatment of intoxication with new psychoactive substances and methamphetamine].

    PubMed

    Flüchter, Peter; Pajonk, Frank-Gerald Bernhard

    2015-03-01

    Fatal outcomes subsequent to the use of new psychoactive suostances are increasingly common in Germany. In this article, we present the clinical effects and associated side effects of the different classes of substances, as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines and methamphetamine, as well as diagnostic aspects and treatment options in case of symptoms of poisoning. PMID:26364395

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

    PubMed

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

    2009-08-01

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

  5. Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging.

    PubMed

    London, Edythe D; Kohno, Milky; Morales, Angelica M; Ballard, Michael E

    2015-12-01

    Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets.

  6. The methamphetamine-sensitive circadian oscillator (MASCO) in mice.

    PubMed

    Tataroglu, Ozgür; Davidson, Alec J; Benvenuto, Luke J; Menaker, Michael

    2006-06-01

    The suprachiasmatic nucleus (SCN) orchestrates synchrony among many peripheral oscillators and is required for circadian rhythms of locomotor activity and many physiological processes. However, the unique effects of methamphetamine (MAP) on circadian behavior suggest the presence of an SCN-independent, methamphetamine-sensitive circadian oscillator (MASCO). Substantial data collected using rat models show that chronic methamphetamine dramatically lengthens circadian period of locomotor activity rhythms and induces rhythms in animals lacking an SCN. However, the anatomical substrate and the molecular components of the MASCO are unknown. The response to MAP is less well studied in mice, a model that would provide the genetic tools to probe the molecular components of this extra-SCN oscillator. The authors tested the effects of chronic MAP on 2 strains of intact and SCN-lesioned mice in constant dark and constant light. Furthermore, they applied various MAP availability schedules to SCN-lesioned mice to confirm the circadian nature of the underlying oscillator. The results indicate that this oscillator has circadian properties. In intact mice, the MASCO interacts with the SCN in a manner that is strain, sex, and dose dependent. In SCN-lesioned mice, it induces robust free-running locomotor rhythmicity, which persists for up to 14 cycles after methamphetamine is withdrawn. In the future, localization of the MASCO and characterization of its underlying molecular mechanism, as well as its interactions with other oscillators in the body, will be essential to a complete understanding of the organization of the mammalian circadian system.

  7. The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding.

    PubMed

    Boctor, Sherin Y; Martinez, Joe L; Koek, Wouter; France, Charles P

    2007-09-24

    Cannabinoid CB(1) receptor antagonists can decrease methamphetamine self-administration. This study examined whether the CB(1) receptor antagonist AM251 [N-(piperidin-1-yl)-5-(4-indophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] modifies reinstatement in rats that previously self-administered methamphetamine. Rats (n=10) self-administered methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 2 schedule. Non-contingent methamphetamine (0.01-1.78 mg/kg, i.v.) yielded responding for saline (reinstatement) that was similar to responding for self-administered methamphetamine. AM251 (0.032-0.32, i.v.) did not affect methamphetamine-induced reinstatement but significantly attenuated Delta(9)-tetrahydrocannabinol (2.0 mg/kg, i.p.)-induced hypothermia. These data fail to support a role for endogenous cannabinoids or cannabinoid CB(1) receptors in reinstatement and, therefore, relapse to stimulant abuse.

  8. Detection of levorotatory methamphetamine and levorotatory amphetamine in urine after ingestion of an overdose of selegiline.

    PubMed

    Fujita, Yuji; Takahashi, Katsuo; Takei, Masao; Niitsu, Hisae; Aoki, Yasuhiro; Onodera, Makoto; Fujino, Yasuhisa; Inoue, Yoshihiro; Endo, Shigeatsu

    2008-10-01

    In this study, we measured the urine concentrations of methamphetamine and amphetamine as metabolites of selegiline after ingestion of an overdose of selegiline. A patient who had developed Parkinson disease took selegiline in a suicide attempt. Analysis by gas chromatography-mass spectrometry (GC-MS) with trifluoroacetic acid-derivatization revealed the presence of methamphetamine and amphetamine in the patient's urine at concentrations of 0.62 microg/ml and 0.25 microg/ml, respectively. To determine the stereospecificity of the methamphetamine and amphetamine, a urine sample was analyzed by GC-MS after derivatization with N-(trifluoroacetyl)-l-prolyl chloride. The methamphetamine and amphetamine were levorotatory in form. The ratio of the methamphetamine to amphetamine concentration in the urine was 2.5. This value is consistent with other case reports of ingestion of selegiline, which suggests that the methamphetamine to amphetamine concentration ratio in urine is useful information for indicating use of selegiline.

  9. Short communication: Methamphetamine treatment increases in vitro and in vivo HIV replication.

    PubMed

    Toussi, Sima Shelly; Joseph, Aviva; Zheng, Jian Hua; Dutta, Monica; Santambrogio, Laura; Goldstein, Harris

    2009-11-01

    To delineate the mechanistic basis for the epidemiological association between methamphetamine use and accelerated progression to AIDS, we evaluated the direct in vitro and in vivo effects of methamphetamine on HIV-1 replication. Methamphetamine administration significantly increased HIV-1 production by both HIV-infected monocytes and CD4 T lymphocytes in vitro. In addition, in vivo methamphetamine treatment increased HIV production and viremia in mice transgenic for a replication-competent HIV provirus and human cyclin T1. Methamphetamine activated transcription of the HIV long terminal repeat (LTR) regulatory region, was associated with nuclear translocation of NF-kappaB. Our results provide further insights into the mechanisms by which methamphetamine accelerates disease course in HIV-infected individuals.

  10. Sex differences in escalation of methamphetamine self-administration: Cognitive and motivational consequences

    PubMed Central

    Reichel, Carmela M.; Chan, Clifford; Ghee, Shannon M.; See, Ronald E.

    2013-01-01

    Rationale Male rats escalate methamphetamine (meth) intake during long access meth self-administration, show enhanced reinstatement of meth seeking, and exhibit meth-induced memory impairments. However, the impact of long access daily meth self-administration on reinstatement and cognitive dysfunction has not been assessed in females, even though clinical studies on meth addiction have shown differences between men and women. Objectives This study determined whether male and freely-cycling female rats: 1) escalate meth-intake in a 6-h daily access period relative to 1-h access; 2) show different sensitivity to meth primed reinstatement after short and long access conditions; and 3) show deficits in novel object and object in place recognition memory. Methods Male and female Long-Evans rats self-administered meth in limited (1-h/day) or extended (6-h/day) daily access sessions. After 21 days, meth access was discontinued and rats entered an abstinence period. On the 7th and 14th days of abstinence, rats were assessed for recognition memory using tests for: a) novel object recognition memory, and b) object-in-place memory. Rats were tested for reinstatement of meth-seeking following extinction of responding. Results Female rats self-administered more meth and escalated intake faster than males during extended, but not limited, daily access. Both males and females in the extended, but not limited, access groups showed memory deficits on both tasks. Female rats showed greater reinstatement to meth-seeking with lower doses of meth priming injections than males. Conclusions Relative to males, females were equally susceptible to meth-induced memory deficits, but exhibited higher meth intake and greater relapse to meth-seeking. PMID:22592902

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

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

  13. Ibogaine blocked methamphetamine-induced hyperthermia and induction of heat shock protein in mice.

    PubMed

    Yu, X; Imam, S Z; Newport, G D; Slikker, W; Ali, S F

    1999-03-27

    Body temperature changes and heat shock protein (HSP-72) induction in the caudate nucleus were studied in female C57BL/6N mice pretreated with ibogaine (50 mg/kg) and sacrificed 48 h. after a single dose of methamphetamine (20 mg/kg). Methamphetamine injection resulted in hyperthermia and induced HSP-72 expression, whereas treatment with ibogaine alone produced hypothermia. The ibogaine followed by methamphetamine injection showed no hyperthermia and decreased HSP-72 expression. These data indicate that pretreatment with ibogaine can completely block methamphetamine-induced hyperthermia and HSP-72 expression in the striatum.

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

    SciTech Connect

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

    2008-03-01

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

  15. 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

    2014-08-01

    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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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.

  19. 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. PMID:25459104

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

    PubMed

    Banks, Matthew L; Blough, Bruce E

    2015-08-01

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

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

    PubMed

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

    2015-01-01

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

  2. Typologies of positive psychotic symptoms in methamphetamine dependence

    PubMed Central

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

    2014-01-01

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

  3. 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

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

    SciTech Connect

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

    2010-12-01

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

  5. 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.

  6. Partial MHC/neuroantigen peptide constructs: a potential neuroimmune-based treatment for methamphetamine addiction.

    PubMed

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

    2013-01-01

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

  7. 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.

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    PubMed

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

    2015-12-01

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

  10. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity

    PubMed Central

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

    2015-01-01

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

  11. Electrochemical Impedance Spectroscopic Sensing of Methamphetamine by a Specific Aptamer

    PubMed Central

    Ebrahimi, Mohsen; Johari-Ahar, Mohammad; Hamzeiy, Hossein; Barar, Jaleh; Mashinchian, Omid; Omidi, Yadollah

    2012-01-01

    Introduction Electrochemical impedance spectroscopy (EIS) is a simple and highly sensitive technique that can be used for evaluation of the aptamer-target interaction even in a label-free approach. Methods To pursue the effectiveness of EIS, in the current study, the folding properties of specific aptamer for methamphetamine (METH) (i.e., aptaMETH) were evaluated in the presence of METH and amphetamine (Amph). Folded and unfolded aptaMETH was mounted on the gold electrode surface and the electron charge transfer was measured by EIS. Results The Ret of methamphetamine-aptaMETH was significantly increased in comparison with other folding conditions, indicating specific detection of METH by aptaMETH. Conclusion Based on these findings, methamphetamine-aptaMETH on the gold electrode surface displayed the most interfacial electrode resistance and thus the most folding situation. This clearly indicates that the aptaMETH can profoundly and specifically pinpoint METH; as a result we suggest utilization of this methodology for fast and cost-effective identification of METH. PMID:23678446

  12. Exposures associated with clandestine methamphetamine drug laboratories in Australia.

    PubMed

    Wright, Jackie; Edwards, John; Walker, Stewart

    2016-09-01

    The clandestine manufacture of methamphetamine in residential homes may represent significant hazards and exposures not only to those involved in the manufacture of the drugs but also to others living in the home (including children), neighbours and first responders to the premises. These hazards are associated with the nature and improper storage and use of precursor chemicals, intermediate chemicals and wastes, gases and methamphetamine residues generated during manufacture and the drugs themselves. Many of these compounds are persistent and result in exposures inside a home not only during manufacture but after the laboratory has been seized or removed. Hence new occupants of buildings formerly used to manufacture methamphetamine may be unknowingly exposed to these hazards. Children are most susceptible to these hazards and evidence is available in the literature to indicate that these exposures may result in immediate and long-term adverse health effects. The assessment of exposure within the home can be undertaken by measuring contaminant levels or collecting appropriate biological data from individuals exposed. To gain a better understanding of the available data and key issues associated with these approaches to the characterisation of exposure, a review of the published literature has been undertaken. PMID:27428841

  13. Methamphetamine-induced structural plasticity in the dorsal striatum.

    PubMed

    Jedynak, Jakub P; Uslaner, Jason M; Esteban, José A; Robinson, Terry E

    2007-02-01

    Repeated exposure to psychostimulant drugs produces long-lasting changes in dendritic structure, presumably reflecting a reorganization in patterns of synaptic connectivity, in brain regions that mediate the psychomotor activating and incentive motivational effects of these drugs, including the nucleus accumbens and prefrontal cortex. However, repeated exposure to psychostimulant drugs also facilitates a transition in the control of some behaviors from action-outcome associations to behavior controlled by stimulus-response (S-R) habits. This latter effect is thought to be due to increasing engagement and control over behavior by the dorsolateral (but not dorsomedial) striatum. We hypothesized therefore that repeated exposure to methamphetamine would differentially alter the density of dendritic spines on medium spiny neurons (MSNs) in the dorsolateral vs. dorsomedial striatum. Rats were treated with repeated injections of methamphetamine, and 3 months later dendrites were visualized using Sindbis virus-mediated green fluorescent protein (GFP) expression in vivo. We report that prior exposure to methamphetamine produced a significant increase in mushroom and thin spines on MSNs in the dorsolateral striatum, but a significant decrease in mushroom spines in the dorsomedial striatum. This may be due to changes in the glutamatergic innervation of these two subregions of the dorsal striatum. Thus, we speculate that exposure to psychostimulant drugs may facilitate the development of S-R habits because this reorganizes patterns of synaptic connectivity in the dorsal striatum in a way that increases control over behavior by the dorsolateral striatum.

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

    PubMed

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

    2007-06-01

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

  15. 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.

  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. Involvement of sigma (sigma) receptors in the acute actions of methamphetamine: receptor binding and behavioral studies.

    PubMed

    Nguyen, Emily C; McCracken, Kari A; Liu, Yun; Pouw, Buddy; Matsumoto, Rae R

    2005-10-01

    Methamphetamine interacts with sigma (sigma) receptors, suggesting that the drug produces some of its physiological and behavioral effects through these sites. Therefore, in the present report, receptor binding and pharmacological studies were performed to characterize the interaction between methamphetamine and sigma receptors. Of the two major sigma receptor subtypes, sigma1 and sigma2, competition binding studies showed that methamphetamine has a 22-fold preferential affinity for the sigma1 subtype. Saturation binding studies using the sigma1 selective radioligand [3H]+-pentazocine showed that in the presence of methamphetamine, there was a significant change in Kd, but not Bmax, suggesting competitive interactions. In behavioral studies, pretreatment of Swiss Webster mice with the sigma1 receptor antagonists, BD1063 or BD1047, significantly attenuated the locomotor stimulatory effects of methamphetamine. Mice that were administered an antisense oligodeoxynucleotide to down-regulate brain sigma1 receptors also exhibited a reduced locomotor stimulatory response to methamphetamine, as compared to control mice receiving mismatch oligonucleotides. Together, the data suggest that sigma1 receptors are involved in the acute actions of methamphetamine and that antagonism of this subtype is sufficient to prevent the locomotor stimulatory effects of methamphetamine. PMID:15939443

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Skeers, Vicki M.

    1992-01-01

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

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

    ERIC Educational Resources Information Center

    Yacoubian, George S.

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Armstrong, Todd A.; Armstrong, Gaylene S.

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  6. Simple HPLC method for detection of trace ephedrine and pseudoephedrine in high-purity methamphetamine.

    PubMed

    Makino, Yukiko

    2012-03-01

    A simple and sensitive HPLC technique was developed for the qualitative determination of ephedrine and pseudoephedrine (ephedrines), used as precursors of clandestine d-methamphetamine hydrochloride of high purity. Good separation of ephedrines from bulk d-methamphetamine was achieved, without any extraction or derivatization procedure on a CAPCELLPACK C18 MGII (250 × 4.6 mm) column. The mobile phase consisted of 50 mM KH2 PO4-acetonitrile (94:6 v/v %) using an isocratic pump system within 20 min for detecting two analytes. One run took about 50 min as it was necessary to wash out overloaded methamphetamine for column conditioning. The analytes were detected by UV absorbance measurement at 210 nm. A sample (20 mg) was simply dissolved in 1 mL of water, and a 50 μL aliquot of the solution was injected into the HPLC. The detection limits for ephedrine and pseudoephedrine in bulk d-methamphetamine were as low as 3 ppm each. This analytical separation technique made it possible to detect ephedrine and/or pseudoephedrine in seven samples of high-purity d-methamphetamine hydrochloride seized in Japan. The presence of trace ephedrines in illicit methamphetamine may strongly indicate a synthetic route via ephedrine in methamphetamine profiling. This method is simple and sensitive, requiring only commonly available equipment, and should be useful for high-purity methamphetamine profiling.

  7. 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. PMID:25704260

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Eitle, David J.; Eitle, Tamela McNulty

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Stretesky, Paul B.

    2009-01-01

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

  11. 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.

  12. Methamphetamine use and HIV risk among substance-abusing offenders in California.

    PubMed

    Farabee, David; Prendergast, Michael; Cartier, Jerome

    2002-01-01

    Recent epidemiological surveys of illicit substance use show a particularly high prevalence of methamphetamine use in the western and southwestern United States-most notably California. Moreover, in their analysis of 1995 Drug Use Forecasting data, Anglin and colleagues (1998) found that methamphetamine was a preferred substance among California arrestees. The present study uses data from 807 state prison inmates in California (32% of whom reported using methamphetamine prior to incarceration) to examine the associations between methamphetamine use and HIV risk behaviors. Methamphetamine users in this sample were significantly more likely than nonusers to have injected drugs during the six months prior to their current incarceration. Among injectors, however, injection-related risks (such as dirty needles and needle sharing, etc.) were not significantly associated with methamphetamine use. However, past six-month sex-related risks were dramatically higher for methamphetamine users. These patterns persisted even after controlling for background differences between the two groups. The results of this study underscore the importance of addressing the higher sex-related HIV/AIDS risk among methamphetamine users undergoing prison-based drug treatment. PMID:12422940

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

    PubMed Central

    Taymoori, Parvaneh; Pashaei, Tahereh

    2016-01-01

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

  14. Longitudinal Modeling of Methamphetamine Use and Sexual Risk Behaviors in Gay and Bisexual Men

    PubMed Central

    Mukherjee, Preetika Pandey; Palamar, Joseph J.

    2015-01-01

    The purpose of the analyses was to examine the associations between methamphetamine and other club drug use with sexual risk taking across time in cohort of gay and bisexual men. Data were collected from a community-based sample. Assessments of unprotected anal intercourse with casual partners, and use of methamphetamine and other illicit drugs, were assessed at baseline, and at 4-month intervals over the course of a year, and were analyzed using hierarchical linear modeling. Methamphetamine use was related to the frequency of unprotected insertive and receptive intercourse with both HIV-positive and status unknown casual partners across time. The association between methamphetamine use and unprotected acts also was more pronounced for HIV-positive participants. These findings suggest that methamphetamine, and unprotected anal intercourse are co-occurring risk behaviors, that potentially heighten the risk of HIV transmission among gay and bisexual men. HIV prevention and intervention should concurrently target both these behaviors. PMID:18661225

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

    PubMed Central

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

    2014-01-01

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

  16. 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

  17. Disruption of striatal glutamatergic/GABAergic homeostasis following acute methamphetamine in mice.

    PubMed

    Pereira, Frederico C; Cunha-Oliveira, Teresa; Viana, Sofia D; Travassos, Ana S; Nunes, Sara; Silva, Carlos; Prediger, Rui Daniel; Rego, A Cristina; Ali, Syed F; Ribeiro, Carlos Alberto Fontes

    2012-01-01

    Methamphetamine leads to functional changes in basal ganglia that are linked to impairment in motor activity. Previous studies from our group and others have shown that a single high-methamphetamine injection induces striatal dopaminergic changes in rodents. However, striatal glutamatergic, GABAergic and serotoninergic changes remain elusive under this methamphetamine regimen. Moreover, nothing is known about the participation of the receptor for advanced glycation end-products (RAGE), which is overexpressed upon synaptic dysfunction and glial response, on methamphetamine-induced striatal dysfunction. The aim of this work was to provide an integrative characterization of the striatal changes in amino acids, monoamines and astroglia, as well as in the RAGE levels, and the associated motor activity profile of C57BL/6 adult mice, 72 h after a single-high dose of methamphetamine (30 mg/kg, i.p.). Our findings indicate, for the first time, that methamphetamine decreases striatal glutamine, glutamate and GABA levels, as well as glutamine/glutamate and GABA/glutamate ratios, while serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels remain unchanged. This methamphetamine regimen also produced dopaminergic terminal degeneration in the striatum, as evidenced by dopamine and tyrosine hydroxylase depletion. Consistently, methamphetamine decreased the locomotor activity of mice, in the open field test. In addition, increased levels of glutamine synthase and glial fibrillary acidic protein were observed. Nevertheless, methamphetamine failed to change RAGE levels. Our results show that acute methamphetamine intoxication induces pronounced changes in the striatal glutamatergic/GABAergic and dopaminergic homeostasis, along with astrocyte activation. These neurochemical and glial alterations are accompanied by impairment in locomotor activity.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-01

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

  1. Prior methamphetamine self-administration attenuates the dopaminergic deficits caused by a subsequent methamphetamine exposure.

    PubMed

    McFadden, Lisa M; Vieira-Brock, Paula L; Hanson, Glen R; Fleckenstein, Annette E

    2015-06-01

    Others and we have reported that prior methamphetamine (METH) exposure attenuates the persistent striatal dopaminergic deficits caused by a subsequent high-dose "binge" METH exposure. The current study investigated intermediate neurochemical changes that may contribute to, or serve to predict, this resistance. Rats self-administered METH or saline for 7 d. On the following day (specifically, 16 h after the conclusion of the final METH self-administration session), rats received a binge exposure of METH or saline (so as to assess the impact of prior METH self-administration), or were sacrificed without a subsequent METH exposure (i.e., to assess the status of the rats at what would have been the initiation of the binge METH treatment). Results revealed that METH self-administration per se decreased striatal dopamine (DA) transporter (DAT) function and DA content, as assessed 16 h after the last self-administration session. Exposure to a binge METH treatment beginning at this 16-h time point decreased DAT function and DA content as assessed 1 h after the binge METH exposure: this effect on DA content (but not DAT function) was attenuated if rats previously self-administered METH. In contrast, 24 h after the binge METH treatment prior METH self-administration: 1) attenuated deficits in DA content, DAT function and vesicular monoamine transporter-2 function; and 2) prevented increases in glial fibrillary acidic protein and DAT complex immunoreactivity. These data suggest that changes 24 h, but not 1 h, after binge METH exposure are predictive of tolerance against the persistence of neurotoxic changes following binge METH exposures.

  2. 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

  3. Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum

    PubMed Central

    Cadet, Jean Lud; McCoy, Michael T.; Cai, Ning Sheng; Krasnova, Irina N.; Ladenheim, Bruce; Beauvais, Genevieve; Wilson, Natascha; Wood, William; Becker, Kevin G.; Hodges, Amber B.

    2009-01-01

    Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2), thyrotropin-releasing hormone (TRH), brain derived neurotrophic factor (BDNF), c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx)-1, and heme oxygenase-1 (Hmox-1). These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to provide some

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-08-01

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

  7. Methamphetamine use, attitudes about condoms, and sexual risk behavior among HIV-positive men who have sex with men.

    PubMed

    Nakamura, Nadine; Mausbach, Brent T; Ulibarri, Monica D; Semple, Shirley J; Patterson, Thomas L

    2011-04-01

    This study examined attitudes about condoms as a moderator of the relationship between methamphetamine use and sexual risk behavior in a sample of 297 HIV-positive, methamphetamine-using men who have sex with men (MSM). To test for a moderating effect of attitudes towards condoms, an interaction term was included in multiple regression analysis along with age, income, negative condom attitudes, frequency of methamphetamine use, and Beck depression score. A post hoc analysis was conducted to determine the relations between methamphetamine use and unprotected sex for persons with more vs. less negative attitudes toward condoms. These analyses indicated that when individuals had more negative attitudes toward condoms, the relation between methamphetamine frequency and unprotected sex was significant, while among participants with less negative attitudes toward condoms, no significant association was found. Addressing methamphetamine-using MSM's attitudes about condoms can serve as a form of harm reduction for those who are not yet ready or willing to discontinue methamphetamine use.

  8. Gender differences in the effect of adult amphetamine on cognitive functions of rats prenatally exposed to methamphetamine.

    PubMed

    Macúchová, E; Nohejlová, K; Slamberová, R

    2014-08-15

    Psychostimulants have been shown to affect brain regions involved in the process of learning and memory consolidation. It has been shown that females are more sensitive to the effects of drugs than males. The aim of our study was to investigate how prenatal methamphetamine (MA) exposure and application of amphetamine (AMP) in adulthood would affect spatial learning of adult female and male rats. Mothers of the tested offspring were exposed to injections of MA (5mg/kg) or saline (SA) throughout the entire gestation period. Cognitive functions of adult rats were evaluated in the Morris Water Maze (MWM) tests. Adult offspring were injected daily with AMP (5mg/kg) or SA through the period of MWM testing. Our data from the MWM tests demonstrates the following. Prenatal MA exposure did not change the learning ability of adult male and female rats. However, AMP administration to adult animals affected cognitive function in terms of exacerbation of spatial learning (increasing the latency to reach the hidden platform, the distance traveled and the search error) only in female subjects. There were sex differences in the speed of swimming. Prenatal MA exposure and adult AMP treatment increased the speed of swimming in female groups greater than in males. Overall, the male subjects showed a better learning ability than females. Thus, our results indicate that the adult AMP treatment affects the cognitive function and behavior of rats in a sex-specific manner, regardless of prenatal exposure.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-10-01

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

  11. 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

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

    PubMed Central

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

    2015-01-01

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

  13. Development and persistence of methamphetamine-conditioned hyperactivity in Swiss-Webster mice.

    PubMed

    Rauhut, Anthony Sean; Bialecki, Victoria

    2011-06-01

    These experiments examined the development and persistence of methamphetamine-conditioned hyperactivity in Swiss-Webster mice. Experiments 1 and 2 examined the development of conditioned hyperactivity, varying the methamphetamine dose (0.25-2.0 mg/kg), the temporal injection parameters (continuous; experiment 1 or intermittent; experiment 2), and the comparison control group (saline; experiment 1 or unpaired; experiment 2). Experiment 3 examined the persistence of methamphetamine-conditioned hyperactivity by comparing mice 1 (immediate) or 28 (delay) days after drug withdrawal. In each experiment, several behavioral measures (vertical counts, distance traveled, and velocity) were recorded and temporal analyses conducted to assess methamphetamine-conditioned hyperactivity. In experiments 1 and 2, it was found that methamphetamine-conditioned hyperactivity was (i) dose-dependent, (ii) detected early in the session, and (iii) detected by a behavioral measure indicative of general activity (i.e. distance traveled), and (iv) varied as a function of the number of conditioning sessions. In experiment 3, it was found that conditioned hyperactivity persisted for 28 days, though was weakened by nonassociative factors, following methamphetamine withdrawal. Collectively, these results suggest that conditioned hyperactivity to methamphetamine is robust and persists after prolonged periods of drug withdrawal in mice. Furthermore, these results are consistent with an excitatory classical conditioning interpretation of conditioned hyperactivity.

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

    PubMed

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

    2015-03-01

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

  15. 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.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  18. Trends in production, trafficking, and consumption of methamphetamine and cocaine in Mexico.

    PubMed

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

    2006-01-01

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

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

    PubMed Central

    Courtney, Kelly E.; Ray, Lara A.

    2014-01-01

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

  20. Trends in production, trafficking, and consumption of methamphetamine and cocaine in Mexico.

    PubMed

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

    2006-01-01

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

  1. Nociceptin attenuates methamphetamine abstinence-induced withdrawal-like behavior in planarians.

    PubMed

    Rawls, Scott M; Baron, Steven; Ding, Zhe; Roth, Christopher; Zaveri, Nurulain; Raffa, Robert B

    2008-06-01

    Planarians display a concentration-related reduction in locomotor activity when amphetamine, cocaine, cannabinoid, or benzodiazepine exposure is abruptly discontinued. In the present study, we tested the hypothesis that abrupt discontinuation of methamphetamine would also cause withdrawal-like behavior in planarians and that the withdrawal-like behavior would be prevented by nociceptin, which has been shown to modulate the effects of methamphetamine in mammals. We observed a concentration-related reduction of locomotor behavior when planarians exposed to methamphetamine (0.1-100 microM) were tested in drug-free water. The withdrawal-like behavior was abolished when methamphetamine (10 microM)-exposed planarians were placed into water containing nociceptin (10 microM) or when planarians co-exposed to methamphetamine (10 microM) and nociceptin (10 microM) were placed into drug-free water. The effects of nociceptin were abolished in the presence of a nociceptin receptor antagonist, JTC-801 (1 microM). Planarians did not display a change in locomotor behavior during exposure to nociceptin (10 microM) or JTC-801 (1 microM) by themselves. These results (1) reveal a functional interaction between nociceptin and methamphetamine in planarians and (2) provide evidence that nociceptin blocks methamphetamine-induced withdrawal-like behavior in planarians through a JTC-801-sensitive mechanism.

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

    PubMed Central

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

    2009-01-01

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

  3. HIV Risk Behavior Among Methamphetamine Users Entering Substance Abuse Treatment in Cape Town, South Africa.

    PubMed

    Meade, Christina S; Lion, Ryan R; Cordero, Daniella M; Watt, Melissa H; Joska, John A; Gouse, Hetta; Burnhams, Warren

    2016-10-01

    South Africa is experiencing a growing methamphetamine problem, and there is concern that methamphetamine use may accelerate HIV transmission. There has been little research on the HIV prevention needs of methamphetamine users receiving substance abuse treatment in South Africa. This study assessed the prevalence and correlates of HIV risk behaviors among 269 methamphetamine users entering substance abuse treatment in two clinics in Cape Town. The prevalence of sexual risk behaviors was high among sexually active participants: 34 % multiple partners, 26 % unprotected intercourse with a casual partner, and 24 % sex trading for money/methamphetamine. The strongest predictor of all sexual risk behaviors was concurrent other drug use. Over half had not been HIV tested in the past year, and 25 % had never been tested, although attitudes toward HIV testing were overwhelmingly positive. This population of primarily heterosexual, non-injecting methamphetamine users is a high-risk group in need of targeted HIV prevention interventions. Substance abuse treatment is an ideal setting in which to reach methamphetamine users for HIV services.

  4. The analysis of BDNF gene polymorphism haplotypes and impulsivity in methamphetamine abusers.

    PubMed

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

    2015-05-01

    An increasing number of evidence showed that genetic factors might contribute to drug abuse vulnerability. Data from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be associated with substance abuse or dependence. To test the hypothesis that the BDNF gene polymorphism is involved in methamphetamine abuse, we compared three single nucleotide polymorphisms (SNPs, rs16917204, rs16917234, and rs2030324) of the BDNF gene in 200 methamphetamine abusers and 219 healthy individuals. We also considered the association of these polymorphisms with impulsivity in methamphetamine abusers using Barratt Impulsivity Scale-11(BIS-11) Chinese version. Individual SNP analysis showed no significant differences in genotype and allele distributions between the methamphetamine abusers and controls. Haplotype analysis of rs16917204-rs16917234-rs2030324 revealed that a major C-C-T haplotype was significantly associated a lower odds of methamphetamine abuse, even after Bonferroni correction. Within the methamphetamine-abuse group, subjects carrying the T allele of rs2030324 genotype had significantly higher motor impulsivity scores of BIS compared to those with the C/C genotype. Our findings suggest that the BDNF gene polymorphism may contribute to the impulsivity in methamphetamine abusers.

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

    PubMed

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

    2016-03-01

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

  6. Acute lead poisoning in two users of illicit methamphetamine

    SciTech Connect

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

    1987-07-31

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

  7. Chronic methamphetamine self-administration disrupts cortical control of cognition.

    PubMed

    Bernheim, Aurelien; See, Ronald E; Reichel, Carmela M

    2016-10-01

    Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse. PMID:27450578

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

    PubMed Central

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

    2012-01-01

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

  9. Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the vesicular monoamine transporter-2.

    PubMed

    Nickell, Justin R; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P

    2010-02-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [(3)H]dihydrotetrabenazine binding, inhibition of [(3)H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (K(i) = 45 nM) inhibiting vesicular [(3)H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC(50) = 0.65 microM; I(max) = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC(50) = 0.42 microM, I(max) = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for

  10. Lobelane Inhibits Methamphetamine-Evoked Dopamine Release via Inhibition of the Vesicular Monoamine Transporter-2S⃞

    PubMed Central

    Nickell, Justin R.; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B.; Zheng, Guangrong; Crooks, Peter A.

    2010-01-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [3H]dihydrotetrabenazine binding, inhibition of [3H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (Ki = 45 nM) inhibiting vesicular [3H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC50 = 0.65 μM; Imax = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC50 = 0.42 μM, Imax = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for the development of a

  11. 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

  12. Methamphetamine-induced striatal dopamine release, behavior changes and neurotoxicity in BALB/c mice.

    PubMed

    Kita, T; Matsunari, Y; Saraya, T; Shimada, K; O'Hara, K; Kubo, K; Wagner, G C; Nakashima, T

    2000-10-01

    The behaviors associated with the neurotoxic effects of methamphetamine were evaluated in BALB/c mice. Hyperthermia and behavioral observations were measured 60 min after each subcutaneous injection of methamphetamine (4x4 or 8 mg/kg) or saline, each given 2 h apart. The behavioral observations included stereotyped behaviors, incidence of hemorrhage in breast, salivation and self-injurious behavior (SIB). Repeated administration of methamphetamine produced these behavioral changes and hyperthermia, but resulted in hypothermia by the final injection (8 mg/kg). In addition, the methamphetamine treatment induced a long-lasting dopamine depletion of similar magnitude in the 4 and 8 mg/kg-treated animals. In a time course study striatal monoamine levels were measured 60 min after each injection of these doses. The first and second injections of methamphetamine (8 mg/kg) produced a drastic increase in striatal 3-methoxytyramine; this failed to occur after the third or fourth injection of the same dose. In contrast, 4 mg/kg of methamphetamine also produced an increase in 3-methoxytyramine after the second and third injections of the drug and, in this case, these were maintained for the duration of the treatment. Striatal 3, 4-dihydroxyphenylacetic acid levels also drastically decreased following both doses of methamphetamine, suggesting inhibition of monoamine oxidase in striatum. Moreover, a single injection of methamphetamine increased striatal 2,3-dihydroxybenzoic acid formation. These results suggest that the incidence of hyperthermia, SIB and striatal dopamine neurotoxicity are closely linked to striatal dopamine release and inhibition of monoamine oxidase produced by methamphetamine in BALB/c mice.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2015-09-01

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

  16. Prepulse inhibition in HIV-1 gp120 transgenic mice after withdrawal from chronic methamphetamine.

    PubMed

    Henry, Brook L; Geyer, Mark A; Buell, Mahalah R; Perry, William; Young, Jared W; Minassian, Arpi

    2014-02-01

    HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both factors are associated with impairment in inhibitory function that continues even after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are induced by acute stimulant administration, but the combined effect of HIV and chronic METH exposure on PPI is not well characterized. We quantified baseline acoustic startle and PPI in mice expressing the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates; thereafter, we administered a chronic regimen of METH or vehicle and tested startle and PPI after 7 days of drug withdrawal. We hypothesized that METH-treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT or gp120tg animals. Before METH administration, drug-naive female gp120tg mice exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice exhibited increased startle compared with other groups. After drug withdrawal, no consistent genotype effect was observed, but METH-treated mice exhibited increased PPI compared with vehicle, in contrast to previous reports of acute METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on factors such as sex, whereas changes in PPI following METH withdrawal may depend on the quantity and duration of drug exposure.

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

    PubMed

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

    2016-10-01

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

  18. The Feasibility of Interventions to Reduce HIV Risk and Drug Use among Heterosexual Methamphetamine Users

    PubMed Central

    Corsi, Karen F.; Lehman, Wayne E.; Min, Sung-Joon; Lance, Shannon P.; Speer, Nicole; Booth, Robert E.; Shoptaw, Steve

    2013-01-01

    This paper reports on a feasibility study that examined contingency management among out-of-treatment, heterosexual methamphetamine users and the reduction of drug use and HIV risk. Fifty-eight meth users were recruited through street outreach in Denver from November 2006 through March 2007. The low sample size reflects that this was a pilot study to see if CM is feasible in an out-of-treatment, street-recruited population of meth users. Secondary aims were to examine if reductions and drug use and risk behavior could be found. Subjects were randomly assigned to contingency management (CM) or CM plus strengths-based case management (CM/SBCM), with follow-up at 4 and 8 months. Participants were primarily White (90%), 52% male and averaged 38 years old. Eighty-three percent attended at least one CM session, with 29% attending at least fifteen. All participants reduced meth use significantly at follow-up. Those who attended more sessions submitted more stimulant-free urines than those who attended fewer sessions. Participants assigned to CM/SBCM attended more sessions and earned more vouchers than clients in CM. Similarly, participants reported reduced needle-sharing and sex risk. Findings demonstrate that CM and SBCM may help meth users reduce drug use and HIV risk. PMID:23493796

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

    PubMed Central

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

    2015-01-01

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

  20. Prepulse inhibition in HIV-1 gp120 transgenic mice after withdrawal from chronic methamphetamine

    PubMed Central

    Henry, Brook L.; Geyer, Mark A.; Buell, Mahalah R.; Perry, William; Young, Jared W.; Minassian, Arpi

    2014-01-01

    HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both factors are associated with impairment in inhibitory function that continues even after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are induced by acute stimulant administration, but the combined effect of HIV and chronic METH exposure on PPI is not well characterized. We quantified baseline acoustic startle and PPI in mice expressing the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates; thereafter, we administered a chronic regimen of METH or vehicle and tested startle and PPI after 7 days of drug withdrawal. We hypothesized that METH-treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT or gp120tg animals. Before METH administration, drug-naive female gp120tg mice exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice exhibited increased startle compared with other groups. After drug withdrawal, no consistent genotype effect was observed, but METH-treated mice exhibited increased PPI compared with vehicle, in contrast to previous reports of acute METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on factors such as sex, whereas changes in PPI following METH withdrawal may depend on the quantity and duration of drug exposure. PMID:24281153

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

    PubMed Central

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

    2015-01-01

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

  2. 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.

  3. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

    PubMed Central

    Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

    2014-01-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

  4. Conceptualizing Social Recovery: Recovery Routes of Methamphetamine Users

    PubMed Central

    Boeri, Miriam; Gibson, David; Boshears, Paul

    2014-01-01

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

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

    SciTech Connect

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

    2014-03-01

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

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

    PubMed

    Killinger, Bryan A; Moszczynska, Anna

    2016-02-01

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

  7. 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

  8. Effects of methamphetamine and methyldopa on ethanol induced hypothermia in mice.

    PubMed

    Ageel, A M; Ginawi, O T

    1985-02-01

    The effects of D-methamphetamine HCl (1, 2 and 4 mg/kg, i.p.) and alpha-methyldopa (1, 2 and 4 mg/kg, i.p.) on rectal temperature and on ethanol (3 g/kg, i.p.)-induced hypothermia have been investigated in mice. Methamphetamine caused a dose-dependent hyperthermia, but methyldopa induced hypothermia, which decreased with increases in dose. Methamphetamine antagonized the hypothermic effect of ethanol, but methyldopa (1 and 2 mg/kg) did not affect it. Methyldopa (4 mg/kg), however, reversed ethanol hypothermia. Ethanol pretreatment significantly potentiated the hypothermic effect of methyldopa (4 mg/kg), and it prevented methamphetamine-induced hyperthermia. A possible central action for the tested drugs on biogenic monoamines and a peripheral component in their thermoregulatory effects are discussed in this report.

  9. Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure.

    PubMed

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

    2016-06-01

    Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131-141, 2016. © 2016 Wiley Periodicals, Inc. PMID:27297291

  10. Low concentrations of methamphetamine detectable in urine in the presence of high concentrations of amphetamine.

    PubMed

    Jemionek, John F; Addison, Joseph; Past, Marilyn R

    2009-04-01

    Twenty-two urine specimens reported by military drug-testing laboratories for the presence of high concentrations of amphetamine only were subject to further analysis for the presence of methamphetamine. The 22 urine specimens had concentrations of amphetamine in the range of 28,028 to 241,142 ng/mL. The specimens were also assayed for the respective isomeric ratio of d (S) and l (R) amphetamine and methamphetamine. The results suggest that urine specimens containing high concentrations of amphetamine in which the urine concentration ratio of methamphetamine to amphetamine is less than 0.5% with similar isomeric distribution of d-(S) and l-(R) amphetamine and methamphetamine, respectively, may not necessarily indicate polydrug use.

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

    PubMed

    Rau, Thomas; Ziemniak, John; Poulsen, David

    2016-01-01

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

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

    PubMed

    Kuribara, H; Tadokoro, S

    1983-02-01

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

  13. 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.

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

    NASA Technical Reports Server (NTRS)

    Brown, Patricia A.; Comparin, Jeffrey H.

    1995-01-01

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

  15. Incubation of methamphetamine and palatable food craving after punishment-induced abstinence.

    PubMed

    Krasnova, Irina N; Marchant, Nathan J; Ladenheim, Bruce; McCoy, Michael T; Panlilio, Leigh V; Bossert, Jennifer M; Shaham, Yavin; Cadet, Jean L

    2014-07-01

    In a rat model of drug craving and relapse, cue-induced drug seeking progressively increases after withdrawal from methamphetamine and other drugs, a phenomenon termed 'incubation of drug craving'. However, current experimental procedures used to study incubation of drug craving do not incorporate negative consequences of drug use, which is a common factor promoting abstinence in humans. Here, we studied whether incubation of methamphetamine craving is observed after suppression of drug seeking by adverse consequences (punishment). We trained rats to self-administer methamphetamine or palatable food for 9 h per day for 14 days; reward delivery was paired with a tone-light cue. Subsequently, for one group within each reward type, 50% of the lever-presses were punished by mild footshock for 9-10 days, whereas for the other group lever-presses were not punished. Shock intensity was gradually increased over time. Next, we assessed cue-induced reward seeking in 1-h extinction sessions on withdrawal days 2 and 21. Response-contingent punishment suppressed extended-access methamphetamine or food self-administration; surprisingly, food-trained rats showed greater resistance to punishment than methamphetamine-trained rats. During the relapse tests, both punished and unpunished methamphetamine- and food-trained rats showed significantly higher cue-induced reward seeking on withdrawal day 21 than on day 2. These results demonstrate that incubation of both methamphetamine and food craving occur after punishment-induced suppression of methamphetamine or palatable food self-administration. Our procedure can be used to investigate mechanisms of relapse to drug and palatable food seeking under conditions that more closely approximate the human condition. PMID:24584329

  16. Incubation of Methamphetamine and Palatable Food Craving after Punishment-Induced Abstinence

    PubMed Central

    Krasnova, Irina N; Marchant, Nathan J; Ladenheim, Bruce; McCoy, Michael T; Panlilio, Leigh V; Bossert, Jennifer M; Shaham, Yavin; Cadet, Jean L

    2014-01-01

    In a rat model of drug craving and relapse, cue-induced drug seeking progressively increases after withdrawal from methamphetamine and other drugs, a phenomenon termed ‘incubation of drug craving'. However, current experimental procedures used to study incubation of drug craving do not incorporate negative consequences of drug use, which is a common factor promoting abstinence in humans. Here, we studied whether incubation of methamphetamine craving is observed after suppression of drug seeking by adverse consequences (punishment). We trained rats to self-administer methamphetamine or palatable food for 9 h per day for 14 days; reward delivery was paired with a tone-light cue. Subsequently, for one group within each reward type, 50% of the lever-presses were punished by mild footshock for 9–10 days, whereas for the other group lever-presses were not punished. Shock intensity was gradually increased over time. Next, we assessed cue-induced reward seeking in 1-h extinction sessions on withdrawal days 2 and 21. Response-contingent punishment suppressed extended-access methamphetamine or food self-administration; surprisingly, food-trained rats showed greater resistance to punishment than methamphetamine-trained rats. During the relapse tests, both punished and unpunished methamphetamine- and food-trained rats showed significantly higher cue-induced reward seeking on withdrawal day 21 than on day 2. These results demonstrate that incubation of both methamphetamine and food craving occur after punishment-induced suppression of methamphetamine or palatable food self-administration. Our procedure can be used to investigate mechanisms of relapse to drug and palatable food seeking under conditions that more closely approximate the human condition. PMID:24584329

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

    PubMed

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

    2015-01-01

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

  18. Incubation of methamphetamine and palatable food craving after punishment-induced abstinence.

    PubMed

    Krasnova, Irina N; Marchant, Nathan J; Ladenheim, Bruce; McCoy, Michael T; Panlilio, Leigh V; Bossert, Jennifer M; Shaham, Yavin; Cadet, Jean L

    2014-07-01

    In a rat model of drug craving and relapse, cue-induced drug seeking progressively increases after withdrawal from methamphetamine and other drugs, a phenomenon termed 'incubation of drug craving'. However, current experimental procedures used to study incubation of drug craving do not incorporate negative consequences of drug use, which is a common factor promoting abstinence in humans. Here, we studied whether incubation of methamphetamine craving is observed after suppression of drug seeking by adverse consequences (punishment). We trained rats to self-administer methamphetamine or palatable food for 9 h per day for 14 days; reward delivery was paired with a tone-light cue. Subsequently, for one group within each reward type, 50% of the lever-presses were punished by mild footshock for 9-10 days, whereas for the other group lever-presses were not punished. Shock intensity was gradually increased over time. Next, we assessed cue-induced reward seeking in 1-h extinction sessions on withdrawal days 2 and 21. Response-contingent punishment suppressed extended-access methamphetamine or food self-administration; surprisingly, food-trained rats showed greater resistance to punishment than methamphetamine-trained rats. During the relapse tests, both punished and unpunished methamphetamine- and food-trained rats showed significantly higher cue-induced reward seeking on withdrawal day 21 than on day 2. These results demonstrate that incubation of both methamphetamine and food craving occur after punishment-induced suppression of methamphetamine or palatable food self-administration. Our procedure can be used to investigate mechanisms of relapse to drug and palatable food seeking under conditions that more closely approximate the human condition.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Saika, Fumihiro; Kiguchi, Norikazu; Kishioka, Shiroh

    2015-10-01

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

  1. The Relative Reinforcing Strength of Methamphetamine and d-Amphetamine in Monkeys Self-Administering Cocaine

    PubMed Central

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

    2013-01-01

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

  2. Methamphetamine absorption by skin lipids: accumulated mass, partition coefficients, and the influence of fatty acids.

    PubMed

    Parker, K; Morrison, G

    2016-08-01

    Occupants of former methamphetamine laboratories, often residences, may experience increased exposure through the accumulation of the methamphetamine in the organic films that coat skin and indoor surfaces. The objectives of this study were to determine equilibrium partition coefficients of vapor-phase methamphetamine with artificial sebum (AS-1), artificial sebum without fatty acids (AS-2), and real skin surface films, herein called skin oils. Sebum and skin oil-coated filters were exposed to vapor-phase methamphetamine at concentrations ranging from 8 to 159 ppb, and samples were analyzed for exposure time periods from 2 h to 60 days. For a low vapor-phase methamphetamine concentration range of ~8-22 ppb, the equilibrium partition coefficient for AS-1 was 1500 ± 195 μg/g/ppb. For a high concentration range of 98-112 ppb, the partition coefficient was lower, 459 ± 80 μg/g/ppb, suggesting saturation of the available absorption capacity. The low partition coefficient for AS-2 (33 ± 6 μg/g/ppb) suggests that the fatty acids in AS-1 and skin oil are responsible for much high partition coefficients. We predict that the methamphetamine concentration in skin lipids coating indoor surfaces can exceed recommended surface remediation standards even for air concentrations well below 1 ppb.

  3. Sexual Pleasure and Sexual Risk among Women who Use Methamphetamine: A Mixed Methods Study

    PubMed Central

    Lorvick, Jennifer; Bourgois, Philippe; Wenger, Lynn D.; Arreola, Sonya G.; Lutnick, Alexandra; Wechsberg, Wendee M.; Kral, Alex H.

    2012-01-01

    Background The intersection of drug use, sexual pleasure and sexual risk behavior is rarely explored when it comes to poor women who use drugs. This paper explores the relationship between sexual behavior and methamphetamine use in a community-based sample of women, exploring not only risk, but also desire, pleasure and the challenges of overcoming trauma. Methods Quantitative data were collected using standard epidemiological methods (N=322) for community-based studies. In addition, using purposive sampling, qualitative data were collected among a subset of participants (n=34). Data were integrated for mixed methods analysis. Results While many participants reported sexual risk behavior (unprotected vaginal or anal intercourse) in the quantitative survey, sexual risk was not the central narrative pertaining to sexual behavior and methamphetamine use in qualitative findings. Rather, desire, pleasure and disinhibition arose as central themes. Women described feelings of power and agency related to sexual behavior while high on methamphetamine. Findings were mixed on whether methamphetamine use increased sexual risk behavior. Conclusion The use of mixed methods afforded important insights into the sexual behavior and priorities of methamphetamine-using women. Efforts to reduce sexual risk should recognize and valorize the positive aspects of methamphetamine use for some women, building on positive feelings of power and agency as an approach to harm minimization. PMID:22954501

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

    PubMed

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

    2013-09-01

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

  5. Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice.

    PubMed

    Kubota, Yasuhiko; Ito, Chihiro; Sakurai, Eiichi; Sakurai, Eiko; Watanabe, Takehiko; Ohtsu, Hiroshi

    2002-11-01

    We have recently suggested that the brain histamine has an inhibitory role on the behavioral effects of methamphetamine by pharmacological studies. In this study, we used the histidine decarboxylase gene knockout mice and measured the spontaneous locomotor activity, the changes of locomotion by single and repeated administrations of methamphetamine, and the contents of brain monoamines and amino acids at 1 h after a single administration of methamphetamine. In the histidine decarboxylase gene knockout mice, spontaneous locomotor activity during the dark period was significantly lower than in the wild-type mice. Interestingly, methamphetamine-induced locomotor hyperactivity and behavioral sensitization were facilitated more in the histidine decarboxylase gene knockout mice. In the neurochemical study, noradrenaline and O-phosphoserine were decreased in the midbrain of the saline-treated histidine decarboxylase gene knockout mice. On the other hand, single administration of methamphetamine decreased GABA content of the midbrain of the wild-type mice, but did not alter that of histidine decarboxylase gene knockout mice. These results suggest that the histamine neuron system plays a role as an awakening amine in concert with the noradrenaline neuron system, whereas it has an inhibitory role on the behavioral effects of methamphetamine through the interaction with the GABAergic neuron system.

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

    PubMed

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

    2016-05-01

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

  7. Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.

    PubMed

    Mori, Tomohisa; Narita, Minoru; Onodera, Kenji; Suzuki, Tsutomu

    2002-06-01

    The role of the histaminergic system in the discriminative stimulus effects of cocaine and methamphetamine was examined in rats trained to discriminate between saline and cocaine (10 mg/kg) or methamphetamine (1.0 mg/kg). L-histidine (400 mg/kg), a precursor of histamine, significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. Previous studies have revealed the existence of several histamine receptor types, H1-, H2-, and H3-receptors. These enhancing effects of L-histidine on the discriminative stimulus effects of cocaine and methamphetamine were attenuated by 5.0 mg/kg of pyrilamine (an H1-receptor antagonist), but not by 1.0 mg/kg of zolantidine (an H2-receptor antagonist), suggesting that these enhancing effects of L-histidine were mediated through the activation of H1-receptors. Thioperamide (7.5 mg/kg), an H3-receptor antagonist, also significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. However, neither pyrilamine nor zolantidine affected the enhancing effects of thioperamide, unlike the results attained with L-histidine. Therefore our findings suggest that the histaminergic system may modify the discriminative stimulus effects of cocaine and methamphetamine mediated through H1- and H3-receptors.

  8. [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.

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

    PubMed

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

    2013-09-01

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

  10. Underlying mechanism of combined effect of methamphetamine and morphine on lethality in mice and therapeutic potential of cooling.

    PubMed

    Namiki, Mizuho; Mori, Tomohisa; Sawaguchi, Toshiko; Ito, Shinobu; Suzuki, Tadashi

    2005-10-01

    An increase in polydrug abuse is a major problem worldwide. A previous study showed that coadministration of methamphetamine and morphine induced lethality in rodents and humans. However, the underlying mechanisms by which the lethality is increased by the coadministration of methamphetamine and morphine have not been fully understood. Therefore, the present study was designed to determine the mechanism of increased lethality induced by methamphetamine and morphine. Coadministered methamphetamine and morphine increased the lethality by more than 70% in BALB/c mice. Pretreatment with NMDA-receptor antagonists, such as MK-801 and 3-((R)-2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP), and benzamide [poly(ADP-ribose) polymerase (PARP) inhibitor] significantly attenuated the increased lethality induced by methamphetamine and morphine. Furthermore, the lethal effect induced by methamphetamine and morphine was completely attenuated by immediate cooling after the coadministration of methamphetamine and morphine. It has been reported that methamphetamine-induced neurotoxicity can be blocked by lowering the temperature, and this effect might be mediated by a reduction of release of free radicals. These results suggest that activation of NMDA receptors and PARP play an important role in the increased lethality induced by methamphetamine and morphine.

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

    PubMed Central

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

    2015-01-01

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

  12. Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology.

    PubMed

    Nguyen, Jacques D; Aarde, Shawn M; Cole, Maury; Vandewater, Sophia A; Grant, Yanabel; Taffe, Michael A

    2016-10-01

    Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.

  13. Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology.

    PubMed

    Nguyen, Jacques D; Aarde, Shawn M; Cole, Maury; Vandewater, Sophia A; Grant, Yanabel; Taffe, Michael A

    2016-10-01

    Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine. PMID:27277119

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

    PubMed Central

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

    2015-01-01

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

  15. Methamphetamine increases basal ganglia iron to levels observed in aging.

    PubMed

    Melega, William P; Laćan, Goran; Harvey, Dennis C; Way, Baldwin M

    2007-10-29

    Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.

  16. Methamphetamine-using felons: Psychosocial and behavioral characteristics

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-05-01

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

  18. The vesicular monoamine transporter-2: an important pharmacological target for the discovery of novel therapeutics to treat methamphetamine abuse.

    PubMed

    Nickell, Justin R; Siripurapu, Kiran B; Vartak, Ashish; Crooks, Peter A; Dwoskin, Linda P

    2014-01-01

    Methamphetamine abuse escalates, but no approved therapeutics are available to treat addicted individuals. Methamphetamine increases extracellular dopamine in reward-relevant pathways by interacting at vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine uptake and promote dopamine release from synaptic vesicles, increasing cytosolic dopamine available for reverse transport by the dopamine transporter (DAT). VMAT2 is the target of our iterative drug discovery efforts to identify pharmacotherapeutics for methamphetamine addiction. Lobeline, the major alkaloid in Lobelia inflata, potently inhibited VMAT2, methamphetamine-evoked striatal dopamine release, and methamphetamine self-administration in rats but exhibited high affinity for nicotinic acetylcholine receptors (nAChRs). Defunctionalized, unsaturated lobeline analog, meso-transdiene (MTD), exhibited lobeline-like in vitro pharmacology, lacked nAChR affinity, but exhibited high affinity for DAT, suggesting potential abuse liability. The 2,4-dicholorophenyl MTD analog, UKMH-106, exhibited selectivity for VMAT2 over DAT, inhibited methamphetamine-evoked dopamine release, but required a difficult synthetic approach. Lobelane, a saturated, defunctionalized lobeline analog, inhibited the neurochemical and behavioral effects of methamphetamine; tolerance developed to the lobelane-induced decrease in methamphetamine self-administration. Improved drug-likeness was afforded by the incorporation of a chiral N-1,2-dihydroxypropyl moiety into lobelane to afford GZ-793A, which inhibited the neurochemical and behavioral effects of methamphetamine, without tolerance. From a series of 2,5-disubstituted pyrrolidine analogs, AV-2-192 emerged as a lead, exhibiting high affinity for VMAT2 and inhibiting methamphetamine-evoked dopamine release. Current results support the hypothesis that potent, selective VMAT2 inhibitors provide the requisite preclinical behavioral profile for evaluation as pharmacotherapeutics for

  19. The Vesicular Monoamine Transporter-2: An Important Pharmacological Target for the Discovery of Novel Therapeutics to Treat Methamphetamine Abuse

    PubMed Central

    Nickell, Justin R.; Siripurapu, Kiran B.; Vartak, Ashish; Crooks, Peter A.; Dwoskin, Linda P.

    2014-01-01

    Methamphetamine abuse escalates, but no approved therapeutics are available to treat addicted individuals. Methamphetamine increases extracellular dopamine in reward-relevant pathways by interacting at vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine uptake and promote dopamine release from synaptic vesicles, increasing cytosolic dopamine available for reverse transport by the dopamine transporter (DAT). VMAT2 is the target of our iterative drug discovery efforts to identify pharmacotherapeutics for methamphetamine addiction. Lobeline, the major alkaloid in Lobelia inflata, potently inhibited VMAT2, methamphetamine-evoked striatal dopamine release, and methamphetamine self-administration in rats but exhibited high affinity for nicotinic acetylcholine receptors (nAChRs). Defunctionalized, unsaturated lobeline analog, meso-transdiene (MTD), exhibited lobeline-like in vitro pharmacology, lacked nAChR affinity, but exhibited high affinity for DAT, suggesting potential abuse liability. The 2,4-dicholorophenyl MTD analog, UKMH-106, exhibited selectivity for VMAT2 over DAT, inhibited methamphetamine-evoked dopamine release, but required a difficult synthetic approach. Lobelane, a saturated, defunctionalized lobeline analog, inhibited the neurochemical and behavioral effects of methamphetamine; tolerance developed to the lobelane-induced decrease in methamphetamine self-administration. Improved drug-likeness was afforded by the incorporation of a chiral N-1,2-dihydroxypropyl moiety into lobelane to afford GZ-793A, which inhibited the neurochemical and behavioral effects of methamphetamine, without tolerance. From a series of 2,5-disubstituted pyrrolidine analogs, AV-2-192 emerged as a lead, exhibiting high affinity for VMAT2 and inhibiting methamphetamine-evoked dopamine release. Current results support the hypothesis that potent, selective VMAT2 inhibitors provide the requisite preclinical behavioral profile for evaluation as pharmacotherapeutics for

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

    PubMed

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

    2016-04-01

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

  1. 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.

  2. 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

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

    PubMed

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

    2016-04-01

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

  4. Effects of light, food, and methamphetamine on the circadian activity rhythm in mice.

    PubMed

    Pendergast, Julie S; Yamazaki, Shin

    2014-04-10

    The circadian rhythm of locomotor activity in mice is synchronized to environmental factors such as light and food availability. It is well-known that entrainment of the activity rhythm to the light-dark cycle is attained by the circadian pacemaker in the suprachiasmatic nucleus (SCN). Locomotor activity is also controlled by two extra-SCN oscillators; periodic food availability entrains the food-entrainable oscillator (FEO) and constant consumption of low-dose methamphetamine reveals the output of the methamphetamine-sensitive circadian oscillator (MASCO). In this study, we sought to investigate the relationship between the SCN, FEO, and MASCO by examining the combinatorial effects of light, food restriction, and/or methamphetamine on locomotor activity. To investigate coupling between the SCN and FEO, we tested whether food anticipatory activity, which is the output of the FEO, shifted coordinately with phase shifts of the light-dark cycle. We found that the phase of food anticipatory activity was phase-delayed or phase-advanced symmetrically with the respective shift of the light-dark cycle, suggesting that the FEO is strongly coupled to the SCN and the phase angle between the SCN and FEO is maintained during ad libitum feeding. To examine the effect of methamphetamine on the output of the FEO, we administered methamphetamine to mice undergoing restricted feeding and found that food-entrained activity was delayed by methamphetamine treatment. In addition, restricted feeding induced dissociation of the MASCO and SCN activity rhythms during short-term methamphetamine treatment, when these rhythms are typically integrated. In conclusion, our data suggest that the outputs of the SCN, FEO and MASCO collectively drive locomotor activity.

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

    PubMed Central

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

    2016-01-01

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

  6. Substance-Use and Sexual Harm-Reduction Strategies of Methamphetamine-Using Men Who Have Sex with Men and Inject Drugs

    PubMed Central

    Wilkerson, J. Michael; Noor, Syed W.; Breckenridge, Ellen D.; Adeboye, Adeniyi A.; Rosser, B. R. Simon

    2015-01-01

    Research indicates that men who have sex with men (MSM), use methamphetamine, and inject drugs are at high risk of HIV infection and they employ multiple harm reduction strategies simultaneously to reduce that risk. In this study, we identified substances most commonly injected and harm reduction strategies most often employed by methamphetamine-using MSM, used latent class analysis (LCA) to identify patterns of harm reduction strategies, and differentiated MSM within each class by individual characteristics. We analyzed data from 284 participants who completed an online cross-sectional survey. Commonly injected substances were methamphetamine (93.70%), gamma-hydroxybutyrate/gamma-butyrolactone (41.55%), flunitrazepam (40.49%), and cocaine (35.56%). The substance-use strategies most often used were avoidance of sharing needles (85.92%) and use of bleach to clean drug paraphernalia (64.08%). The sexual strategy most often used was avoidance of condomless anal intercourse (CAS) while using drugs (77.11%). Using an LCA approach, we identified three classes distinguishable by age, race/ethnicity, and outness. One class (19%) employed lay strategies to reduce harm: they avoided sharing drug preparation equipment, serosorted when sharing needles and equipment or having CAS, and practiced withdrawal when having CAS. The largest class (53%) combined sexual and substance use strategies: they avoided sharing needles, used bleach to clean needles and equipment, avoided CAS when using drugs, and used extra lubricant when having CAS. The remaining class (28%) employed only substance-use rather than sexual strategies. More MSM of color were in the substance-use class, and more young, non-Hispanic White men were in the lay class. The low utilization of sexual strategies by younger, non-Hispanic White men in the lay class is concerning as they are just as likely as older, non-Hispanic White men in the combined class to have CAS with multiple male partners. Interventionists should

  7. Methamphetamine-Associated Congestive Heart Failure: Increasing Prevalence and Relationship of Clinical Outcomes to Continued Use or Abstinence.

    PubMed

    Sliman, Sean; Waalen, Jill; Shaw, David

    2016-10-01

    The purpose of this study was to determine the prevalence of methamphetamine-associated congestive heart failure (MAC) and to evaluate the relationship between methamphetamine abuse and EF and functional status over time. A retrospective review of records from 2009 to 2014 was carried out. Prevalence of methamphetamine abuse among all patients admitted with CHF was calculated for each of the 6 years of the study (n = 141) and was compared with prevalence of cocaine abuse and alcohol abuse. For patients with two or more admissions during the entire time period, the trajectories of NYHA functional class and EF over time were determined (n = 58). MAC has significantly increased from 1.8 to 5.6 % of total CHF patients admitted (n = 3705). Among patients who stopped using methamphetamine, NYHA functional class significantly improved, while among patients who continued methamphetamine use, NYHA was significantly worsened (p < 0.001). Significantly more patients with improved EF stopped using methamphetamine than continued (p = 0.05). There was a significant increase in the prevalence of MAC during the study period for all CHF patients admitted in our hospital system. Continued methamphetamine use is associated with worsening functional status, while cessation of methamphetamine is associated with improvement in functional status.

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

    ERIC Educational Resources Information Center

    Butler, Rachael; Wheeler, Amanda; Sheridan, Janie

    2010-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  10. Cocaine and methamphetamine produce different patterns of subjective and cardiovascular effects.

    PubMed

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

    2005-09-01

    The stimulant effects of cocaine and methamphetamine are mediated by changes in synaptic concentrations of brain monoamines; however, the drugs alter monoamine levels via different mechanisms. This study examined the subjective and cardiovascular responses produced by investigational administration of cocaine or methamphetamine, in order to examine the onset and patterns of subjective and cardiovascular responses. Subjects included 14 non-treatment seeking cocaine-dependent and 11 non-treatment seeking methamphetamine-dependent volunteers. As part of ongoing research studies, cocaine and methamphetamine subjects received cocaine (40 mg, IV) or methamphetamine (30 mg, IV), respectively. Subjective and cardiovascular responses were assessed for 30 min and 60 min, respectively. The data reveal significant within groups differences for all subjective effects and cardiovascular effects (p<0.05). Significant between group differences in subjective effects were observed for "Any Drug Effect" (p<.008 for group, and p<.029 for group x time), for "High" (p<.002 for group, and p<.0001 for group x time) and for "Stimulated" (p<.001 for group, and p<.006 for group x time). Significant between group differences in cardiovascular effects were observed for Systolic blood pressure (p<.0001 for group, and p<.002 for group x time), Diastolic blood pressure (p<.0001 for group, though p=NS for group x time), and for Heart Rate (p<.0001 for group, and p<.0001 for group x time). The only difference between the groups for placebo was for heart rate, where there was a significant group x time effect (p<.005). Taken together, the data reveal that the subjective effects of cocaine tended to peak and then decline more rapidly than those produced by methamphetamine. The subjective effects of methamphetamine tended to rise more slowly, and remain elevated longer. Cardiovascular effects of cocaine and methamphetamine had similar onset, but effects of cocaine tended to decline more rapidly

  11. BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation

    PubMed Central

    Manning, Elizabeth E.; van den Buuse, Maarten

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH) users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous (HET) mutant mice has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and wildtype (WT) littermates were treated during young adulthood with METH and, following a 2-week break, prepulse inhibition (PPI) was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH) disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine (APO) or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioral endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behavior. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the

  12. Low environmental temperatures or pharmacologic agents that produce hypothermia decrease methamphetamine neurotoxicity in mice.

    PubMed

    Ali, S F; Newport, G D; Holson, R R; Slikker, W; Bowyer, J F

    1994-09-26

    Recently we have reported that methamphetamine (METH) neurotoxicity in rats depends on the environmental temperature. Here, we evaluate whether a cold environment (4 degrees C) or drugs which chloride and glutamate ion channel function block METH neurotoxicity in mice. Adult male CD mice received METH i.p. (4 x 10 mg/kg METH at 23 degrees C along with saline. 2.5 mg/kg (+)-MK-801, 40 mg/kg phenobarbital or 2.5 mg/kg diazepam and either 4 x 10 or 4 x 20 mg/kg METH at 4 degrees C). Multiple injections of METH (4 x 10 mg/kg i.p.) at room temperature (23 degrees C) produced a significant depletion of dopamine (DA) in striatum at 24, 72 h, 1 and 2 weeks. Three days post 4 x 10 mg/kg METH at 23 degrees C, an 80% decrease in striatal dopamine (DA) occurred while the same dose at 4 degrees C produced only a 20% DA decrease, and 4 x 20 mg/kg METH at 4 degrees C produced a 54% DA decrease. At 23 degrees C (+)MK-801 completely blocked while phenobarbital (40% decrease) and diazepam (65% decrease) partially blocked decreases in striatal DA produced by 4 x 10 mg/kg METH. Decreases in DOPAC and HVA were similar to the decreases in DA after METH and antagonists. Multiple injections of METH (4 x 10 mg/kg, i.p.) at room temperature also produced a significant depletion of serotonin (5-HT) in striatum at 24, 72 h, 1 and 2 weeks. This depletion of 5-HT at room temperature was blocked either by changing the environmental temperature to 4 degrees C, or by pretreatment with MK-801, diazepam and phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Effects of L-carnitine pretreatment in methamphetamine and 3-nitropropionic acid-induced neurotoxicity.

    PubMed

    Binienda, Zbigniew K; Przybyla, Beata D; Robinson, Bonnie L; Salem, Nadia; Virmani, Ashraf; Amato, Antonino; Ali, Syed F

    2006-08-01

    Adult, male Sprague-Dawley rats were injected with 3-ni-tropropionic acid (3-NPA) at 30 mg/kg or methamphetamine (METH) at 20 mg/kg alone or following pretreatment with L-cartnitine (LC) at 100 mg/kg. Rectal temperature was measured before and 4 h following treatment. Animals were sacrificed at 4 h posttreatment. Monoamine neurotransmitters, dopamine (DA) and serotonin (5-HT), and their metabolites were analyzed in the striatum using high-performance liquid chromatography method coupled with electrochemical detection (HPLC/ED). Transcripts of several genes related to DA metabolism were quantified using real time reverse transciption polymerase chain reaction (RT-PCR). Core temperature decreased significantly after 3-NPA acid and increased in METH-treated rats (P < 0.05). Temperature change at 4 h exhibited a significant LC effect for 3-NPA, preventing hypothermia (P < 0.05) and no effect for METH. Concentration of DA and 5-HT, and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), increased significantly in 3-NPA and decreased in METH-treated rats. An increase in DOPAC/DA turnover and serotonin observed after 3-NPA was abolished in LC-/3-NPA-treated rats. In both 3-NPA- and METH-treated rats, LC prevented an increase in DA receptor D(1) gene expression. It appears that carnitine effect preventing hypothermia after 3-NPA treatments may be related not only to its mitochondriotropic actions but also to inhibitory effect on the DA and 5-HT systems activated after the exposure to 3-NPA. The same effect observed at the transcriptional level, at least for the DA receptor D(1), may account for protection against METH toxicity.

  14. Effect of insulin deficiency on the rewarding properties of methamphetamine in streptozotocin-induced diabetic rats.

    PubMed

    Bayat, Amir-Hossein; Haghparast, Abbas

    2015-01-01

    The reward is a positive behavioural response to the pleasant stimuli that can be induced by drugs, such as psychostimulants. Furthermore, diabetes mellitus is a chronic disease that many people throughout the world suffer from. Methamphetamine (METH), as a psychostimulant, engages the dopaminergic system in the reward circuitry and the synapses of dopaminergic terminals can be modified by insulin. In this study, in order to assess the effect of insulin deficiency on reward, streptozotocin (STZ)-induced diabetic animals were used as an appropriate model. One hundred and thirty-two adult male rats were divided into nine groups (three non-diabetic and six diabetic groups) to determine the most effective dose of METH (0.25, 0.5, 1 and 2mg/kg ip), and insulin replacement (10U/kg; ip) during the acquisition period in a conditioned place preference (CPP) paradigm. The diabetes model was induced by a single injection of STZ (60mg/kg; ip). The conditioning score was considered to be the difference in time spent in drug- and saline-paired compartments. The results demonstrated that the most effective doses of METH were 1 and 2mg/kg in non-diabetic animals. Although the place preference was not shown in non-diabetic animals at the dose of 0.5mg/kg, this dose significantly induced place preference to METH in STZ-diabetic rats. Additionally, insulin replacement could reverse the METH-induced CPP in diabetic animals. Our findings suggest that the positive effect of insulin deficiency on METH rewarding properties is dependent on insulin level in part, and the replacement of the insulin in diabetic rats as a treatment can improve the rewarding properties of METH.

  15. Running wheel exercise ameliorates methamphetamine-induced damage to dopamine and serotonin terminals.

    PubMed

    O'Dell, Steven J; Galvez, Bryan A; Ball, Alexander J; Marshall, John F

    2012-01-01

    Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" produces long-lasting damage to dopaminergic and serotonergic terminals. Because previous research has demonstrated that physical activity can ameliorate nigrostriatal injury, this study investigated whether voluntary exercise in rats can alter the monoaminergic damage resulting from a neurotoxic mAMPH binge. Adult male rats were allowed constant access to running wheels or kept in nonwheel cages for three weeks, then given a binge dosing regimen of mAMPH or saline. The rats were returned to their original environments for three additional weeks post-mAMPH. [(125) I]RTI-55 binding and autoradiography was used to quantify dopamine transporters (DAT), and radioimmunocytochemistry was used to quantify striatal tyrosine hydroxylase (TH). Binge mAMPH treatment significantly reduced striatal DAT and TH in a regionally specific pattern; with greatest effects in ventral caudate-putamen (CP) and relative sparing of the nucleus accumbens septi (NAc). The effects of mAMPH on striatal DAT and TH were ameliorated in the running, compared to the sedentary, animals. Also, mAMPH was found to reduce [(125) I]RTI-55 binding to serotonin transporters (SERT) in frontoparietal cortex, and this too was significantly attenuated by exercise. Additional correlational analyses showed that the post-mAMPH running of individual animals predicted the amelioration of striatal DAT and TH as well as frontoparietal SERT. Overall, voluntary exercise significantly diminished mAMPH-induced forebrain monoaminergic damage. The significant correlations between post-mAMPH exercise and markers of monoaminergic terminal integrity provide novel evidence that voluntary exercise may exert beneficial effects on behavior in recovering mAMPH addicts.

  16. Methamphetamine potentiates behavioral and electrochemical responses after mild traumatic brain injury in mice.

    PubMed

    Shen, Hui; Harvey, Brandon K; Chiang, Yung-Hsiao; Pick, Chaim G; Wang, Yun

    2011-01-12

    We previously demonstrated that high doses of methamphetamine (MA) exacerbate damage induced by severe brain trauma. The purpose of the present study was to examine if MA, at low dosage, affected abnormalities in locomotor activity and dopamine turnover in a mouse model of mild traumatic brain injury (mTBI). Adult male CD1 mice were treated with MA (5 mg/kgi.p.) or vehicle 30-min prior to mTBI, conducted by dropping a 30 g metal weight onto the temporal skull, anterior the right ear. At 15 min after mTBI, animals were put into locomotor activity chambers for up to 72 h. During the first 3 h, mTBI alone, compared with vehicle control, did not alter total distance travelled. Treatment with MA significantly increased locomotor activity in the control animals during the first 3 h; mTBI reduced MA-induced hyperactivity. In contrast, at 2 and 3 days after injury, mTBI or MA alone reduced locomotor activity. Co-treatment with MA and mTBI further reduced this activity, suggesting a differential and temporal behavioral interaction between MA and mTBI during acute and subacute phases after injury. Dopamine and DOPAC levels in striatal tissue were analyzed using HPLC-ECD. At 1h after mTBI or injection, DA was not altered but DOPAC level and DOPAC/DA turnover ratios were significantly reduced. Co-treatment with MA further reduced the DOPAC/DA ratio. At 36 h after injury, mTBI increased tissue DA levels, but reduced DOPAC levels and DOPAC/DA ratios. Co-treatment with MA further reduced DOPAC/DA ratios in striatum. In conclusion, our data suggest that low dosage of MA worsens the suppression of locomotor responses and striatal dopamine turnover after mTBI.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-06-01

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

  19. Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges.

    PubMed

    Fujikawa, Denson G; Pais, Emil S; Aviles, Ernesto R; Hsieh, Kung-Chiao; Bashir, Muhammad Tariq

    2016-01-01

    We have evidence that methamphetamine (METH)-induced neuronal death is morphologically necrotic, not apoptotic, as is currently believed, and that electrographic seizures may be responsible. We administered 40mg/kg i.p. to 12 male C57BL/6 mice and monitored EEGs continuously and rectal temperatures every 15min, keeping rectal temperatures <41.0°C. Seven of the 12 mice had repetitive electrographic seizure discharges (RESDs) and 5 did not. The RESDs were often not accompanied by behavioral signs of seizures-i.e., they were often not accompanied by clonic forelimb movements. The 7 mice with RESDs had acidophilic neurons (the H&E light-microscopic equivalent of necrotic neurons by ultrastructural examination) in all of 7 brain regions (hippocampal CA1, CA2, CA3 and hilus, amygdala, piriform cortex and entorhinal cortex), the same brain regions damaged following generalized seizures, 24h after METH administration. The 5 mice without RESDs had a few acidophilic neurons in 4 of the 7 brain regions, but those with RESDs had significantly more in 6 of the 7 brain regions. Maximum rectal temperatures were comparable in mice with and without RESDs, so that cannot explain the difference between the two groups with respect to METH-induced neuronal death. Our data show that METH-induced neuronal death is morphologically necrotic, that EEGs must be recorded to detect electrographic seizure activity in rodents without behavioral evidence of seizures, and that RESDs may be responsible for METH-induced neuronal death.

  20. State dependent effect of transcranial direct current stimulation (tDCS) on methamphetamine craving.

    PubMed

    Shahbabaie, Alireza; Golesorkhi, Mehrshad; Zamanian, Behnam; Ebrahimpoor, Mitra; Keshvari, Fatemeh; Nejati, Vahid; Fregni, Felipe; Ekhtiari, Hamed

    2014-10-01

    Transcranial direct current stimulation (tDCS) has been shown to modulate subjective craving ratings in drug dependents by modification of cortical excitability in dorsolateral prefrontal cortex (DLPFC). Given the mechanism of craving in methamphetamine (meth) users, we aimed to test whether tDCS of DLPFC could also alter self-reported craving in abstinent meth users while being exposed to meth cues. In this double-blinded, crossover, sham-controlled study, thirty two right-handed abstinent male meth users were recruited. We applied 20 min 'anodal' tDCS (2 mA) or 'sham' tDCS over right DLPFC in a random sequence while subjects performed a computerized cue-induced craving task (CICT) starting after 10 min of stimulation. Immediate craving was assessed before the stimulation, after 10 min of tDCS, and after tDCS termination by visual analog scale (VAS) of 0 to 100. Anodal tDCS of rDLPFC altered craving ratings significantly. We found a significant reduction of craving at rest in real tDCS relative to the sham condition (p = 0.016) after 10 min of stimulation. On the other hand, cue-induced VAS craving was rated significantly higher in the real condition in comparison with sham stimulation (p = 0.012). Our findings showed a state dependent effect of tDCS: while active prefrontal tDCS acutely reduced craving at rest in the abstinent meth users, it increased craving during meth-related cue exposure. These findings reflect the important role of the prefrontal cortex in both cue saliency evaluation and urge to meth consumption.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Ande, Anusha; Wang, Lei; Vaidya, Naveen K.; Li, Weihua; Kumar, Santosh; Kumar, Anil

    2016-01-01

    Cytochrome P450 3A4 (CYP3A4) is the major drug metabolic enzyme, and is involved in the metabolism of antiretroviral drugs, especially protease inhibitors (PIs). This study was undertaken to examine the effect of methamphetamine on the binding and metabolism of PIs with CYP3A4. We showed that methamphetamine exhibits a type I spectral change upon binding to CYP3A4 with δAmax and KD of 0.016±0.001 and 204±18 μM, respectively. Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. We then studied the effect of methamphetamine binding on PIs with CYP3A4. Our results showed that methamphetamine alters spectral binding of nelfinavir but not the other type I PIs (lopinavir, atazanavir, tipranavir). The change in spectral binding for nelfinavir was observed at both δAmax (0.004±0.0003 vs. 0.0068±0.0001) and KD (1.42±0.36 vs.2.93±0.08 μM) levels. We further tested effect of methamphetamine on binding of 2 type II PIs; ritonavir and indinavir. Our results showed that methamphetamine alters the ritonavir binding to CYP3A4 by decreasing both the δAmax (0.0038±0.0003 vs. 0.0055±0.0003) and KD (0.043±0.0001 vs. 0.065±0.001 nM), while indinavir showed only reduced KD in presence of methamphetamine (0.086±0.01 vs. 0.174±0.03 nM). Furthermore, LC-MS/MS studies in high CYP3A4 human liver microsomes showed a decrease in the formation of hydroxy ritonavir in the presence of methamphetamine. Finally, CYP3A4 docking with lopinavir and ritonavir in the absence and presence of methamphetamine showed that methamphetamine alters the docking of ritonavir, which is consistent with the results obtained from spectral binding and metabolism studies. Overall, our results demonstrated differential effects of methamphetamine on the binding and metabolism of PIs with CYP3A4. These findings have clinical implication in terms of drug dose adjustment of antiretroviral medication, especially with ritonavir

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

    PubMed

    Nookala, Anantha R; Li, Junhao; Ande, Anusha; Wang, Lei; Vaidya, Naveen K; Li, Weihua; Kumar, Santosh; Kumar, Anil

    2016-01-01

    Cytochrome P450 3A4 (CYP3A4) is the major drug metabolic enzyme, and is involved in the metabolism of antiretroviral drugs, especially protease inhibitors (PIs). This study was undertaken to examine the effect of methamphetamine on the binding and metabolism of PIs with CYP3A4. We showed that methamphetamine exhibits a type I spectral change upon binding to CYP3A4 with δAmax and KD of 0.016±0.001 and 204±18 μM, respectively. Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. We then studied the effect of methamphetamine binding on PIs with CYP3A4. Our results showed that methamphetamine alters spectral binding of nelfinavir but not the other type I PIs (lopinavir, atazanavir, tipranavir). The change in spectral binding for nelfinavir was observed at both δAmax (0.004±0.0003 vs. 0.0068±0.0001) and KD (1.42±0.36 vs.2.93±0.08 μM) levels. We further tested effect of methamphetamine on binding of 2 type II PIs; ritonavir and indinavir. Our results showed that methamphetamine alters the ritonavir binding to CYP3A4 by decreasing both the δAmax (0.0038±0.0003 vs. 0.0055±0.0003) and KD (0.043±0.0001 vs. 0.065±0.001 nM), while indinavir showed only reduced KD in presence of methamphetamine (0.086±0.01 vs. 0.174±0.03 nM). Furthermore, LC-MS/MS studies in high CYP3A4 human liver microsomes showed a decrease in the formation of hydroxy ritonavir in the presence of methamphetamine. Finally, CYP3A4 docking with lopinavir and ritonavir in the absence and presence of methamphetamine showed that methamphetamine alters the docking of ritonavir, which is consistent with the results obtained from spectral binding and metabolism studies. Overall, our results demonstrated differential effects of methamphetamine on the binding and metabolism of PIs with CYP3A4. These findings have clinical implication in terms of drug dose adjustment of antiretroviral medication, especially with ritonavir

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

    PubMed

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

    2016-08-01

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

  5. Famprofazone as the source of methamphetamine and amphetamine in urine specimen collected during sport competition.

    PubMed

    Tseng, Ying Lung; Lin, Chien-Tzong; Wang, Sheng-Meng; Liu, Ray H

    2007-03-01

    During a sport competition event in Taiwan, one urine specimen was found positive for both methamphetamine (2688 ng/mL) and amphetamine (462 ng/mL). The specimen donor claimed that she had taken Gewolen (a nonprescription drug manufactured in Taiwan) for treating abdominal pain and the medication was presented. Laboratory investigation confirmed that Gewolen contains famprofazone, which is known to metabolize to methamphetamine and amphetamine and is included in the prohibited list of the World Anti-Doping Agency. Study on the excretion profiles of three volunteers ingesting 50 mg famprofazone produced the following patterns similar to that observed in the case specimen: (a) the ratio of methamphetamine to amphetamine was approximately 6 to 1; (b) d- and l-enantiomers of both methamphetamine and amphetamine were present, while the amount of l-methamphetamine was 3-4-fold greater than its counterpart. The data suggested that famprofazone (as the ingredient of Gewolen) was likely the source of the prohibited drugs found in the case specimen.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2013-10-25

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

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

    PubMed Central

    Lamonica, Aukje K.; Boeri, Miriam

    2012-01-01

    This study examines patterns of use of prescription drugs and methamphetamine. We drew our sample from a study about 130 active and inactive methamphetamine users and focused on 16 participants with a recent history of methamphetamine and prescription drug use. We collected in-depth interviews to explore relationships in use trajectory patterns. The qualitative methods we used in this study followed the constant comparison process developed by grounded theory methods and analytical ethnography, which is based on familiarity with the social setting and developing propositions while conducting a research study. We used a triangulation of methods and analysis and included qualitative data, such as participant observation notes and in-depth interviews, as well as quantitative data that we collected in drug history matrices. Five themes emerged from the coding of the interview transcripts: (1) sequential polydrug use; (2) concurrent polydrug use (3) temporary substitution of preferred drug; (4) consequential-based use; and (5) switching from using methamphetamine to using prescription drugs. The trajectory patterns of methamphetamine and prescription drug use complicates treatment significantly. PMID:23285312

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

    PubMed

    Duff, Cameron; Moore, David

    2015-01-01

    This article is interested in how notions of the 'public' are conceived, marshalled and enacted in drug-treatment responses to methamphetamine use in Melbourne, Australia. After reviewing qualitative data collected among health-care providers and methamphetamine consumers, we draw on the work of Michael Warner to argue that services for methamphetamine consumers in Melbourne betray ongoing tensions between 'public' and 'counterpublic' constituencies. Our analysis indicates that these tensions manifest in two ways: in the management of 'street business' in the delivery of services and in negotiating the meaning of health and the terms of its restoration or promotion. Reflecting these tensions, while the design of services for methamphetamine consumers is largely modelled on public health principles, the everyday experience of these services may be more accurately characterised in terms of what Kane Race has called 'counterpublic health'. Extending Race's analysis, we conclude that more explicit focus on the idea of counterpublic health may help local services engage with methamphetamine consumers in new ways, providing grounds for novel outreach, harm-reduction and treatment strategies. PMID:24948593

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

    PubMed

    Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael

    2016-06-01

    There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. PMID:27039212

  11. A comparison of adolescent methamphetamine and other substance users in Hawai'i.

    PubMed

    Kim, Richard J; Jackson, David S

    2008-11-01

    Methamphetamine use continues to be a significant problem for adolescents in Hawai'i, especially among Native Hawaiians and other Asian and Pacific Islanders. However, no research has compared the unique characteristics of these methamphetamine (MA) users to other substance users, which could contribute to enhanced treatment approaches. Utilizing a sample of adolescent treatment clients, this study compared those who have ever used and those who have never used methamphetamines on various domains. Results showed that girls were significantly more likely to use methamphetamines than other substances. Native Hawaiians and other Pacific Islanders were more likely to use methamphetamines as well, although the difference was not statistically significant. MA users reported significantly more homelessness and prior treatment episodes. While no differences were found in arrest rates or days in jail/prison/juvenile detention in the past 90 days, MA users scored significantly higher on all self-reported crime indices. MA users also scored significantly higher on all substance problem and mental health indices, and reported significantly poorer health. Implications for future research and treatment are discussed.

  12. Chromatographic and mass spectral studies on methoxy methyl methamphetamines related to 3,4-methylenedioxymethamphetamine.

    PubMed

    Awad, Tamer; Deruiter, Jack; Clark, C Randall

    2007-09-01

    The methoxy methyl methamphetamines are a unique set of compounds having an isobaric relationship with the controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA or Ecstasy). The various isomeric forms of the methoxy methyl methamphetamines have mass spectra essentially equivalent to 3,4-MDMA, all have molecular weight of 193 and major fragment ions in their electron ionization mass spectra at m/z 58 and 135/136. Mass spectral differentiation of 3,4-MDMA from some of the methoxy methyl methamphetamines was possible after formation of the perfluoroacyl derivatives, pentafluoropropionamides (PFPA) and heptafluorobutyramides (HFBA). Perfluoroacyl derivatization provided unique and characteristic mass spectral fragment ions when the methoxy group is substituted at the 2- or 4-position of the aromatic ring relative to the alkylamine side chain group. Perfluoroacyl derivatization did not offer any characteristic ions for discrimination of 3,4-MDMA from the 3-methoxy ring substituted methyl methamphetamines. Gas chromatographic separation on non-polar stationary phases successfully resolved subsets of the methoxy methyl methamphetamines, based on ring position of the methoxy group, from 2,3- and 3,4-MDMA as the PFPA and HFBA derivatives.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-06-01

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

  15. Crystal methamphetamine and sexual sociality in an urban gay subculture: an elective affinity.

    PubMed

    Green, Adam Isaiah; Halkitis, Perry N

    2006-01-01

    This paper draws on 49 qualitative interviews to explore the contextual antecedents of methamphetamine use in a sample of gay and bisexual Manhattan men. The paper distinguishes itself from the public health literature on crystal methamphetamine use in this population by shifting the analytic focus from individual-level factors of drug use to the role of social context. While individual-level factors--including self esteem and social awkwardness--are related to methamphetamine use, we argue that these factors arise in and are exacerbated by interactional pressures attendant to Manhattan's gay sexual subculture, which revolve around the expectation of peak sexual performance. Because methamphetamine is associated with increased self-esteem, increased libido, greater sexual endurance, diminished sexual inhibition, and a higher threshold for pain, the drug is used strategically by gay and bisexual men to negotiate sexual sociality and increase sexual pleasure. Hence, we suggest that there exists an elective affinity between Manhattan's gay sexual subculture and the particular pharmacological effects of methamphetamine-whereby the former strongly favours the latter as a systematic pattern of response. In turn, this relationship is linked to unsafe sexual practices or the social conditions that put gay men 'at risk of risk' of HIV infection.

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

    PubMed

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

    2015-03-15

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

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

    PubMed Central

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

    2010-01-01

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

  18. 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.

  19. Methamphetamine and fluoxetine treatment of a child with attention-deficit hyperactivity disorder and obsessive-compulsive disorder.

    PubMed

    Bussing, R; Levin, G M

    1993-01-01

    ABSTRACT An 11-year-old child with obsessive-compulsive disorder, major depression, and attentiondeficit hyperactivity disorder was successfully treated with a combination of fluoxetine (mean 30 mg daily) and methamphetamine (sustained release 10 mg daily). Methamphetamine was selected because of the desirability of avoiding stimulants whose commercial formulations contain food dyes (this child appeared sensitive to tartrazine in dextroamphetamine and other agents), whose effects on hepatic metabolism were minimal (unlike methylphenidate) and whose mechanism of action is reliably rapid (unlike pemoline). Although methamphetamine carries the stigma of an abusable drug and has been implicated in neurotoxicity in animals when used at extremely high doses, methamphetamine may have certain advantages over other psychostimulants in some clinical situations. The combined use of fluoxetine and methamphetamine did not appear to be associated with significant adverse effects.

  20. 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

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

    PubMed

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

    2016-01-01

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

  2. The glial cell modulators, ibudilast and its amino analog, AV1013, attenuate methamphetamine locomotor activity and its sensitization in mice.

    PubMed

    Snider, Sarah E; Vunck, Sarah A; van den Oord, Edwin J C G; Adkins, Daniel E; McClay, Joseph L; Beardsley, Patrick M

    2012-03-15

    Over 800,000 Americans abuse the psychomotor stimulant, methamphetamine, yet its abuse is without an approved medication. Methamphetamine induces hypermotor activity, and sensitization to this effect is suggested to represent aspects of the addiction process. Methamphetamine's regulation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels may be partially responsible for its behavioral effects, and compounds that inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP, can alter methamphetamine-induced behaviors. Methamphetamine also activates glial cells and causes a subsequent increase in pro-inflammatory cytokine levels. Modulation of glial cell activation is associated with changes in behavioral responses, and substances that oppose inflammatory activity can attenuate drug-induced behaviors. Ibudilast (aka AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), inhibits both PDE and glial pro-inflammatory activity. Ibudilast's amino analog, AV1013, modulates similar glial targets but negligibly inhibits PDE. The present study determined whether ibudilast and AV1013 would attenuate methamphetamine-induced locomotor activity and its sensitization in C57BL/6J mice. Mice were treated b.i.d. with ibudilast (1.8-13 mg/kg), AV1013 (10-56 mg/kg) or their vehicles intraperitoneally for 7 days, beginning 48 h before 5 days of daily 1-h locomotor activity tests. Each test was initiated by either a methamphetamine (3 mg/kg) or a saline injection. Ibudilast significantly (P<0.05) reduced the acute, chronic, and sensitization effects of methamphetamine's locomotor activity without significantly affecting activity by itself. AV1013 had similar anti-methamphetamine effects, suggesting that glial cell activity, by itself, can modulate methamphetamine's effects and perhaps serve as a medication target for its abuse.

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

    PubMed

    Dwyer, Robyn; Moore, David

    2013-05-01

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

  4. Male contraception

    PubMed Central

    Mathew, Vivek; Bantwal, Ganapathi

    2012-01-01

    Contraception is an accepted route for the control of population explosion in the world. Traditionally hormonal contraceptive methods have focused on women. Male contraception by means of hormonal and non hormonal methods is an attractive alternative. Hormonal methods of contraception using testosterone have shown good results. Non hormonal reversible methods of male contraception like reversible inhibition of sperm under guidanceare very promising. In this article we have reviewed the current available options for male contraception. PMID:23226635

  5. Examining the Relationships Between Prenatal Methamphetamine Exposure, Early Adversity, and Child Neurobehavioral Disinhibition

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed

    Hrubá, L; Schutová, B; Šlamberová, R

    2012-01-18

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

  8. Condoms - male

    MedlinePlus

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

  9. American Indian Methamphetamine and other Drug use in the Southwestern United States

    PubMed Central

    Forcehimes, A.A.; Venner, K.L; Bogenschutz, M.P.; Foley, K.; Davis, M. P.; Houck, J. M.; Willie, E. L.; Begaye, P.

    2012-01-01

    Background To investigate the extent of methamphetamine and other drug use among American Indians (AI) in the Four Corners region, we developed collaborations with Southwestern tribal entities and treatment programs in and around New Mexico. Methods (1) We held nine focus groups, mostly with Southwest AI participants (N=81) from three diverse New Mexico communities to understand community members, treatment providers, and clients/relatives views on methamphetamine (2) We conducted a telephone survey of staff (N=100) from agencies across New Mexico to assess perceptions of methamphetamine use among people working with AI populations. (3) We collected and analyzed self-reported drug use data from 300 AI clients/relatives who completed the Addiction Severity Index (ASI) in the context of treatment at three diverse addiction treatment programs. Results Each focus group offered a unique perspective about the effect of drugs and alcohol on each respective community. Though data from the phone surveys and ASIs suggested concerning rates of methamphetamine use, with women more adversely affected by substance use in general, alcohol was identified as the biggest substance use problem for AI populations in the Southwest. Conclusions There appears to be agreement that methamphetamine use is a significant problem in these communities, but that alcohol is much more prevalent and problematic. There was less agreement about what should be done to prevent and treat methamphetamine use. Future research should attend to regional and tribal differences due to variability in drug use patterns, and should focus on identifying and improving dissemination of effective substance use interventions. PMID:21988577

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

    PubMed

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

    2009-01-01

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

  11. Dysregulation of D₂-mediated dopamine transmission in monkeys after chronic escalating methamphetamine exposure.

    PubMed

    Groman, Stephanie M; Lee, Buyean; Seu, Emanuele; James, Alex S; Feiler, Karen; Mandelkern, Mark A; London, Edythe D; Jentsch, J David

    2012-04-25

    Compulsive drug-seeking and drug-taking are important substance-abuse behaviors that have been linked to alterations in dopaminergic neurotransmission and to impaired inhibitory control. Evidence supports the notions that abnormal D₂ receptor-mediated dopamine transmission and inhibitory control may be heritable risk factors for addictions, and that they also reflect drug-induced neuroadaptations. To provide a mechanistic explanation for the drug-induced emergence of inhibitory-control deficits, this study examined how a chronic, escalating-dose regimen of methamphetamine administration affected dopaminergic neurochemistry and cognition in monkeys. Dopamine D₂-like receptor and dopamine transporter (DAT) availability and reversal-learning performance were measured before and after exposure to methamphetamine (or saline), and brain dopamine levels were assayed at the conclusion of the study. Exposure to methamphetamine reduced dopamine D₂-like receptor and DAT availability and produced transient, selective impairments in the reversal of a stimulus-outcome association. Furthermore, individual differences in the change in D₂-like receptor availability in the striatum were related to the change in response to positive feedback. These data provide evidence that chronic, escalating-dose methamphetamine administration alters the dopamine system in a manner similar to that observed in methamphetamine-dependent humans. They also implicate alterations in positive-feedback sensitivity associated with D₂-like receptor dysfunction as the mechanism by which inhibitory control deficits emerge in stimulant-dependent individuals. Finally, a significant degree of neurochemical and behavioral variation in response to methamphetamine was detected, indicating that individual differences affect the degree to which drugs of abuse alter these processes. Identification of these factors ultimately may assist in the development of individualized treatments for substance dependence.

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

    PubMed

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

    2015-12-01

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

  13. A genetic animal model of differential sensitivity to methamphetamine reinforcement

    PubMed Central

    Shabani, Shkelzen; Dobbs, Lauren K; Ford, Matthew M; Mark, Gregory P; Finn, Deborah A; Phillips, Tamara J

    2012-01-01

    Sensitivity to reinforcement from methamphetamine (MA) likely influences risk for MA addiction, and genetic differences are one source of individual variation. Generation of two sets of selectively bred mouse lines for high and low MA drinking has shown that genetic factors influence MA intake, and pronounced differences in sensitivity to rewarding and aversive effects of MA play a significant role. Further validation of these lines as a unique genetic model relevant to MA addiction was obtained using operant methods to study MA reinforcement. High and low MA drinking line mice were used to test the hypotheses that: 1) oral and intracerebroventricular (ICV) MA serve as behavioral reinforcers, and 2) MA exhibits greater reinforcing efficacy in high than low MA drinking mice. Operant responses resulted in access to an MA or non-MA drinking tube or intracranial delivery of MA. Behavioral activation consequent to orally consumed MA was determined. MA available for consumption maintained higher levels of reinforced instrumental responding in high than low MA drinking line mice, and MA intake in the oral operant procedure was greater in high than low MA drinking line mice. Behavioral activation was associated with amount of MA consumed during operant sessions. High line mice delivered more MA via ICV infusion than did low line mice across a range of doses. Thus, genetic risk factors play a critical role in the reinforcing efficacy of MA and the oral self-administration procedure is suitable for delineating genetic contributions to MA reinforcement. PMID:22280875

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Distribution of methamphetamine and amphetamine in drug abusers' head hair.

    PubMed

    Lee, Sooyeun; Han, Eunyoung; Park, Yonghoon; Choi, Hwakyung; Chung, Heesun

    2009-09-10

    In order to aid the interpretation of hair results from methamphetamine (MA) abusers the MA and amphetamine (AP) concentrations in 2070 hair samples were statistically evaluated. The MA and AP concentrations in hair were put into three groups arbitrarily representing low, medium and high ranges and the metabolite-to-parent drug ratios of each group were examined. The concentration ranges proposed here were also applied to the interpretation of five authentic cases. The low, medium and high ranges of MA were 0.5-4.2, 4.2-24.5 and 24.5-608.9 ng/mg and those of AP were 0.1-0.4, 0.4-1.7 and 1.7-41.4 ng/mg. The AP-to-MA ratios showed large variation but a tendency that it decreased as the MA ranges increased. This evaluation was very useful to presume the severity of individuals' MA abuse and to provide law enforcement agencies more understandable information. It could also facilitate the court's decision regarding specific circumstances surrounding the drug-related crimes.

  17. Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration.

    PubMed

    Jung, Bae Dong; Shin, Eun-Joo; Nguyen, Xuan-Khanh Thi; Jin, Chun-Hui; Bach, Jae-Hyung; Park, Seok Joo; Nah, Seung-Yeol; Wie, Myung-Bok; Bing, Guoying; Kim, Hyoung-Chun

    2010-01-01

    Accumulated evidence has indicated that neuroinflammation is one of the important etiologic factors of Parkinson's disease (PD). Earlier studies have employed the inflammogen lipopolysaccharide (LPS) to induce inflammation of dopaminergic neurons. Methamphetamine (MA) dopaminergic toxicity similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity is frequently cited as a model of PD. In the present study, we examined whether striatal LPS exposure potentiates MA-induced dopaminergic toxicity. Combined treatment with LPS and MA significantly potentiates behavioral impairment and dopaminergic deficit. However, this combination did not significantly alter the other monoaminergic systems (e.g., serotonin, norepinephrine, and histamine). Consistently, microglial activation, labeled by F4/80 or Iba-1 in the nigrostriatal region was more pronounced with the combined treatment of LPS and MA compared to either treatment alone, but this combination did not significantly alter the microglial activation in other brain regions (e.g., hippocampus, dorsal raphe nuclei, and locus ceruleus). Furthermore, neuroinflammation, oxidative stress, and pro-apoptotic changes in the striatum were more accentuated with combined treatment of LPS and MA compared to either treatment alone. In addition, it is important that cytoplasmic accumulation of alpha-synuclein was observed in the substantia nigra of mice treated with LPS plus MA, and that L-Dopa treatment significantly attenuated behavioral changes and dopaminergic deficits induced by LPS plus MA. These results suggest that combined treatment of LPS with MA is a potential animal model for PD.

  18. The Complex Interaction between Methamphetamine Abuse and HIV-1 pathogenesis

    PubMed Central

    Passaro, Ryan Colby; Pandhare, Jui; Qian, Han-Zhu; Dash, Chandravanu

    2016-01-01

    The global HIV/AIDS pandemic has claimed the lives of an estimated 35 million people. A significant barrier for combating this global pandemic is substance use since it is associated with HIV transmission, delayed diagnosis/initiation of therapy, and poor adherence to therapy. Clinical studies also suggest a link between substance use and HIV-disease progression/AIDS-associated mortality. Methamphetamine (METH) use is one of the fastest-growing substance use problems in the world. METH use enhances high-risk sexual behaviors, therefore increases the likelihood of HIV-1 acquisition. METH use is also associated with higher viral loads, immune dysfunction, and antiretroviral resistance. Moreover, METH use has also been correlated with rapid progression to AIDS. However, direct effects of METH on HIV-1 disease progression remains poorly understood because use of METH and other illicit drugs is often associated with reduced/non adherence to ART. Nevertheless, in vitro studies demonstrate that METH increases HIV-1 replication in cell cultures and animal models. Thus, it has been proposed that METH’s potentiating effects on HIV-1 replication may in part contribute to the worsening of HIV-1 pathogenesis. However, our recent data demonstrate that METH inhibits HIV-1 replication in CD4+ T cells and challenges this paradigm. Thus, the goal of this review is to systematically examine the published literature to better understand the complex interaction between METH abuse and HIV-1 disease progression. PMID:25850893

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

    PubMed

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

    2007-04-01

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

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

    PubMed

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

    2016-01-01

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

  1. Primary and substance-induced psychotic disorders in methamphetamine users.

    PubMed

    Hides, Leanne; Dawe, Sharon; McKetin, Rebecca; Kavanagh, David J; Young, Ross McD; Teesson, Maree; Saunders, John B

    2015-03-30

    This study investigates the rates of primary psychotic disorders (PPD) and substance-induced psychotic disorders (SIPDs) in methamphetamine (MA) users accessing needle and syringe programs (NSPs). The aim was to determine if there are systematic differences in the characteristics of MA users with PPDs and SIPDs compared to those with no psychotic disorder. Participants were 198 MA users reporting use in the previous month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders (PRISM-IV). Current psychiatric symptoms and substance use were also measured. Just over half (n=101) of participants met DSM-IV criteria for a lifetime psychotic disorder, including 81 (80%) with a SIPD and 20 (20%) with a PPD. Those with a younger age of onset of weekly MA use were at increased risk of a lifetime SIPD. A current psychotic disorder was found in 62 (39%), comprising 49 SIPDs (79%) and 13 PPDs (21%). MA users with a current PPD were more likely to have received psychiatric treatment in the past month than those with a current SIPD, despite a similar level of psychotic symptom severity. A high proportion of MA users accessing NSPs have psychotic disorders, the majority of which are substance-induced.

  2. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization.

    PubMed

    Adkins, D E; McClay, J L; Vunck, S A; Batman, A M; Vann, R E; Clark, S L; Souza, R P; Crowley, J J; Sullivan, P F; van den Oord, E J C G; Beardsley, P M

    2013-11-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In this study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine (MA)-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate, FDR <0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent MA levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization.

  3. Pregnancy and Fetal Loss Reported by Methamphetamine-Using Women

    PubMed Central

    Brecht, Mary-Lynn; Herbeck, Diane M

    2014-01-01

    To better understand substance use disorder treatment needs of pregnant and parenting women who use methamphetamine (MA), this paper describes pregnancy histories and fetal losses for women who were treated for MA use (N = 153) with reference to a national sample, and describes their drug use, sexual risk behaviors, and mental health status. MA users reported an average of 4.6 total pregnancies and 2.1 fetal losses, whereas women in a general population survey reported 3.2 and 1.2, respectively. Higher numbers of pregnancies and fetal losses were correlated with specific substance abuse and mental health problems including early sexual abuse and cognitive problems. The combination of MA users’ especially high numbers of pregnancies, fetal losses, and rates of risk behaviors suggest high social and health care costs for this population. Prenatal care may provide a vector through which women can be connected to risk reduction interventions and gender-responsive treatment services addressing substance use and mental health needs. PMID:24855369

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

    PubMed

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

    2015-01-01

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

  5. Exercise protects against methamphetamine-induced aberrant neurogenesis

    PubMed Central

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. Prenatal exposure: The effects of prenatal cocaine and methamphetamine exposure on the developing child.

    PubMed

    Smith, Lynne M; Santos, Lucinda S

    2016-06-01

    Prenatal substance use remains a significant issue in the United States. Initial reports regarding prenatal cocaine and methamphetamine exposure suggested profound adverse effects on child development. However, subsequent prospective, longitudinal investigations have found more subtle effects. What follows is a brief review of the health, growth, behavioral, and intellectual outcomes for children exposed to prenatal cocaine and prenatal methamphetamine. Factors that may mitigate or intensify subtle adverse effects manifested in exposed children will also be discussed. Birth Defects Research (Part C) 108:142-146, 2016. © 2016 Wiley Periodicals, Inc. PMID:27345014

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

    PubMed

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

    2012-11-30

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

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

    PubMed

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

    2012-11-30

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

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

    PubMed

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

    2013-11-01

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

  11. Development of a reference material using methamphetamine abusers' hair samples for the determination of methamphetamine and amphetamine in hair.

    PubMed

    Lee, Sooyeun; Park, Yonghoon; Yang, Wonkyung; Han, Eunyoung; Choe, Sanggil; In, Sangwhan; Lim, Miae; Chung, Heesun

    2008-04-01

    In the present study, we developed a reference material (RM) using authentic hair samples for the determination of methamphetamine (MA) and its main metabolite, amphetamine (AP) in human hair. MA abusers' hair samples were collected, homogenized and finally bottled. The concentration of each bottle was determined using two extraction methods, agitation with 1% HCl in methanol at 38 degrees C and ultrasonication with methanol/5M HCl (20:1), followed by gas chromatography/mass spectrometry (GC-MS) after derivatization with trifluoroacetic anhydride (TFAA). Both analytical procedures were fully validated and their extraction efficiency was compared. The homogeneity of analytes was evaluated and their property values were determined with their uncertainties. The two methods were acceptable to analyze MA and AP in human hair through the validation and comparative studies using spiked and authentic hair samples as well as NIST SRM 2379 certified reference material. Satisfying homogeneity was reached for MA and AP in the prepared RM. Finally, a human hair RM containing MA and AP is prepared at the level of 7.64+/-1.24 and 0.54+/-0.07 ng/mg, respectively. This material can be useful in forensic laboratories for internal quality control and external quality assurance.

  12. Distribution of methamphetamine and its metabolite amphetamine in acute and subacute ethanol-methamphetamine combination abuse model rats.

    PubMed

    Liang, Man; Liu, Yan; Zheng, Na; Ananda, Sunnassee; Liu, Liang

    2012-01-01

    The aim of this study is to investigate the distribution of methamphetamine (MA) and its metabolite amphetamine (AP) in rat models of acute and subacute MA-ethanol combination abuse. Rats were fed with 20% ethanol for 4 weeks (chronic active-drinking group), and MA was injected intraperitoneally into chronically drinking and normal rats over 5 and 14 days, respectively. Then the rats from the acute and subacute combination abuse groups were euthanized, and ethanol, MA, and AP concentrations in samples were quantified. Except for the similar ethanol concentrations among acute and subacute groups, the MA and AP levels between groups were quite different. The concentrations of MA and AP in rats' liver, lung, kidney, and brain were much higher than other tissues, regardless of combination with ethanol. Also, MA and AP levels in subacute rats groups were higher than those in acute groups, and the levels of MA and the formation of AP in rats subjected to the combination abuse with ethanol were higher than in MA-only intoxicated rats. We conclude that ethanol has no bearing on the MA and AP distribution in body fluids and tissues, yet it can increase MA levels and markedly accelerate the formation of AP in combination-abuse rats. Comparing the acute and subacute combination-abuse rats' samples, it can be deduced that various accumulated amounts of MA and AP were unaffected by ethanol, even after multi-dose injection, regardless of acute or subacute use.

  13. 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.

  14. Enantiomeric separation of methamphetamine and related analogs by capillary zone electrophoresis: intelligence study in routine methamphetamine seizures.

    PubMed

    Cheng, Wing-Chi; Lee, Wing-Man; Chan, Man-Fai; Tsui, Pui; Dao, Kwok-leung

    2002-11-01

    A method for simultaneous enantiomeric separation of ephedrine, pseudoephedrine, and methamphetamine (MA) in a single run by simple capillary zone electrophoresis (CZE) with beta-cyclodextrin as a chiral selector is described. The effects of the buffer pH, phosphate concentration, beta-cyclodextrin concentration, voltage and temperature on the peak resolution were examined. Good enantiomeric resolution was attained for each analyte under our optimized conditions: 15 mM beta-cyclodextrin, 300 mM NaH2PO4 at pH 2.5 with an uncoated capillary (64.5 cm x 50 microm), applied potential at 20 kV and temperature at 30 degrees C. Ultraviolet (UV) detection at a fixed wavelength (200 nm) was employed using a diode array detector. Using phentermine as an internal standard, migration times for all analytes are reproducible within 0.16% for intra-day and 0.6% for inter-day runs. Application of this method to the analysis of confiscated drugs is discussed.

  15. miR-181a is a negative regulator of GRIA2 in methamphetamine-use disorder

    PubMed Central

    Zhang, Kai; Wang, Qingzhong; Jing, Xuxiu; Zhao, Yan; Jiang, Haifeng; Du, Jiang; Yu, Shunying; Zhao, Min

    2016-01-01

    A previous study reported that the miR-181a level in serum was significantly different between patients with methamphetamine-use disorder and healthy controls and that chronic methamphetamine use down-regulates the expression of miR-181a. Bioinformatic analysis predicted that miR-181a might bind the 3′-UTRs of the mRNA transcripts of the human glutamate receptor genes GRIA2 and GABRA1. In this study, we measured the expression of GRIA2 and GABRA1 in patients with methamphetamine-use disorder. In addition, we examined whether miR-181a down-regulates GRIA2 and GABRA1 in a cell-based assay. We further examined the effects of chronic methamphetamine exposure on the expression of miR-181a, GRIA2 and GABRA1. The results demonstrated that serum GRIA2 is higher in patients with methamphetamine-use disorder than in healthy controls. Dual luciferase reporter assays and a cell-based model of methamphetamine exposure also showed that miR-181a directly regulates expression of GRIA2. This study supports the evidence that miR-181a and the glutamate AMPA receptor gene GRIA2 play a critical role in methamphetamine-use disorder. PMID:27767084

  16. Differences in extinction responding and reinstatement of methamphetamine-seeking behavior between Fischer 344 and Lewis rats.

    PubMed

    Kruzich, Paul J; Xi, Jinlei

    2006-03-01

    Fischer 344 (F344) and Lewis (LEW) rats differ in a number of self-administration behaviors. Whether or not these strains differ in methamphetamine-primed reinstatement of extinguished responding is unknown. F344 and LEW rats were trained to self-administer intravenous (i.v.) methamphetamine (0.06 mg/kg) during daily 2-h limited access sessions for 14 days. Following methamphetamine self-administration, subjects underwent a minimum of 6 extinction sessions where responding on the previously active lever resulted in no programmed consequences. Following extinction sessions, we evaluated strain and dose dependency of methamphetamine-primed (0.06, 0.12, or 0.24 mg/kg/i.v.) reinstatement of responding. All subjects received each dose once. Dosing order was determined by utilizing a within-subjects Latin square design. We found partial strain differences in daily methamphetamine self-administration. In addition, F344 rats responded significantly more during the first extinction session compared LEW rats. Last, the LEW rats demonstrated a heightened propensity to reinstate responding following methamphetamine priming injections compared to F344 rats. Our results suggest that genetic background influences differences in methamphetamine-seeking behaviors in rats.

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

    PubMed Central

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

    2013-01-01

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

  18. [Effects of the long-term administration of methamphetamine on body weight, food intake, blood biochemistry and estrous cycle in rats].

    PubMed

    Saito, M; Terada, M; Saito, T R; Takahashi, K W

    1995-10-01

    We have a big problem with the abuse of amphetamine and its close relative, methamphetamine (MAP) in Japan. As an animal model of people who abuse MAP, male and female rats were treated with MAP (0.1-10.0 mg/kg/day) for a long time. The results obtained in the present study were as follows. 1. Body weights in MAP-treated groups showed a dose-dependent decrease with loss of food intake. 2. Food intake in rats treated with MAP decreased, compared with the control, but when treatment with MAP was discontinued, food intake increased dramatically. 3. In a blood biochemistry assay, the turnover of protein and lipid was suppressed in rats after MAP. 4. The administration of MAP appeared to disturb the estrous cycle in female rats.

  19. Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: Locomotor activity, drug discrimination and self-administration

    PubMed Central

    Meyer, AC; Horton, DB; Neugebauer, NM; Wooters, TE; Nickell, JR; Dwoskin, LP; Bardo, MT

    2013-01-01

    Tetrabenazine (TBZ), a benzoquinolizine derivative, binds with high affinity to the vesicular monoamine transporter-2 (VMAT2), inhibiting uptake of cytosolic monoamines. The current study aimed to provide preclinical evidence supporting the potential use of TBZ as a treatment for methamphetamine abuse. Effects of TBZ on function of the dopamine transporter (DAT) and serotonin transporter (SERT) in striatal and hippocampal synaptosomes, respectively, and on VMAT2 function in isolated striatal synaptic vesicles were determined. Effect of TBZ (acute, 0.1 - 3.0 mg/kg, s.c.; repeated, 1.0 mg/kg for 7 days) on locomotor activity in methamphetamine-sensitized rats was assessed. Ability of TBZ (0.1 -3.0 mg/kg; s.c.) or vehicle to decrease the discriminative effect of methamphetamine also was determined. Ability of TBZ (acute, 0.1 - 1.0 mg/kg, s.c.; repeated, 0.1 or 1.0 mg/kg for 7 days) to specifically decrease methamphetamine self-administration was determined; for comparison, a separate group of rats was assessed for effects of TBZ on food-maintained responding. Results show that TBZ was 11-fold more potent inhibiting DAT than SERT, and 2.5-fold more potent inhibiting VMAT2 than DAT. Results from behavioral studies showed that the lowest dose of TBZ transiently increased methamphetamine self-administration, whereas higher TBZ doses decreased methamphetamine self-administration. Also, TBZ at high doses decreased methamphetamine locomotor sensitization and discriminative stimulus effects, as well as food-maintained responding. Thus, despite acting as a potent VMAT2 inhibitor, these preclinical results indicate that TBZ lacks behavioral specificity as an inhibitor of methamphetamine-induced reinforcement, diminishing its viability as a suitable treatment for methamphetamine abuse. PMID:21669212

  20. Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: locomotor activity, drug discrimination and self-administration.

    PubMed

    Meyer, A C; Horton, D B; Neugebauer, N M; Wooters, T E; Nickell, J R; Dwoskin, L P; Bardo, M T

    2011-09-01

    Tetrabenazine (TBZ), a benzoquinolizine derivative, binds with high affinity to the vesicular monoamine transporter-2 (VMAT2), inhibiting uptake of cytosolic monoamines. The current study aimed to provide preclinical evidence supporting the potential use of TBZ as a treatment for methamphetamine abuse. Effects of TBZ on function of the dopamine transporter (DAT) and serotonin transporter (SERT) in striatal and hippocampal synaptosomes, respectively, and on VMAT2 function in isolated striatal synaptic vesicles were determined. Effect of TBZ (acute, 0.1-3.0 mg/kg, s.c.; repeated, 1.0 mg/kg for 7 days) on locomotor activity in methamphetamine-sensitized rats was assessed. Ability of TBZ (0.1-3.0 mg/kg; s.c.) or vehicle to decrease the discriminative effect of methamphetamine also was determined. Ability of TBZ (acute, 0.1-1.0 mg/kg, s.c.; repeated, 0.1 or 1.0 mg/kg for 7 days) to specifically decrease methamphetamine self-administration was determined; for comparison, a separate group of rats was assessed for effects of TBZ on food-maintained responding. Results show that TBZ was 11-fold more potent inhibiting DAT than SERT, and 2.5-fold more potent inhibiting VMAT2 than DAT. Results from behavioral studies showed that the lowest dose of TBZ transiently increased methamphetamine self-administration, whereas higher TBZ doses decreased methamphetamine self-administration. Also, TBZ at high doses decreased methamphetamine locomotor sensitization and discriminative stimulus effects, as well as food-maintained responding. Thus, despite acting as a potent VMAT2 inhibitor, these preclinical results indicate that TBZ lacks behavioral specificity as an inhibitor of methamphetamine-induced reinforcement, diminishing its viability as a suitable treatment for methamphetamine abuse.

  1. Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

    PubMed

    Morales, A M; Kohno, M; Robertson, C L; Dean, A C; Mandelkern, M A; London, E D

    2015-06-01

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

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

    PubMed

    Caprioli, Daniele; Zeric, Tamara; Thorndike, Eric B; Venniro, Marco

    2015-09-01

    Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods, most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hours/day) or extended (6 or 9 hours/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1-0.2 mg/kg/infusion) or palatable food (five pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5-1.0 mg/kg), following a satiety manipulation (palatable food exposure in the home cage) or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards.

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

    PubMed

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2015-09-01

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

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

    PubMed Central

    Caprioli, Daniele; Zeric, Tamara; Thorndike, Eric B; Venniro, Marco

    2015-01-01

    Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hr/day) or extended (6 or 9 hr/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1–0.2 mg/kg/infusion) or palatable food (5 pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5–1.0 mg/kg), following a satiety manipulation (palatable food exposure in the home cage), or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards. PMID:25582886

  5. Temporal relations between methamphetamine use and HIV seroconversion in gay, bisexual, and other men who have sex with men.

    PubMed

    Halkitis, Perry N; Levy, Michael D; Solomon, Todd M

    2016-01-01

    Data from a cross-sectional study of gay, bisexual, and other men who have sex with men who were active methamphetamine users were analyzed to assess temporal relations between HIV seroconversion and initiation of methamphetamine use. Of the 100 men, 58 reported being HIV-positive. Most HIV-positive participants (65%) initiated methamphetamine use after seroconverting. Among those who initiated use before seroconversion, 8 years elapsed between onset of use and time of infection. Findings suggest the need to develop nuanced and targeted interventions aimed at disentangling the "meth-sex" link in this population. Findings also suggest use of the drug as a coping mechanism for those living with HIV.

  6. Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release.

    PubMed

    Yun, Jaesuk

    2014-05-15

    Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function.

  7. The Persian methamphetamine use in methadone treatment in Iran: implication for prevention and treatment in an upper-middle income country.

    PubMed

    Alam-Mehrjerdi, Zahra; Abdollahi, Mohammad

    2015-01-01

    As the most populated Persian Gulf country in West Asia, methamphetamine use in methadone maintenance treatment (MMT) is a new health concern in Iran. Methamphetamine use in MMT can originate in methadone misconceptions or the stimulant effects of methamphetamine use. Several research studies have highlighted the prevalence of methamphetamine use in Iran and conducting further studies on this issue is being developed. Opiate use is treated with MMT. But, there is no effective pharmacological treatment for methamphetamine use and cognitive-behavioral interventions have still remained the best practice. As a psychostimulant drug, methamphetamine use can lead to poor treatment outcomes or even treatment failure among patients in MMT. Therefore, the implementation of methamphetamine education and prevention programs in MMT is required. Prescribing adequate methadone dose and the treatment of comorbidities as well as, doing a series of activities outside treatment is underscored. Methamphetamine use has a chronic nature and methamphetamine treatment is a long-term procedure with a high rate of relapse. Therefore, the implementation of long-term motivational interviewing, teaching necessary skills to prevent relapse and case management is highlighted. A long-term collaboration between treatment teams, patients and their families is suggested to manage methamphetamine use in MMT.

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

    PubMed Central

    Northrop, Nicole A.; Yamamoto, Bryan K.

    2015-01-01

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

  9. Effects of novelty and methamphetamine on conditioned and sensory reinforcement

    PubMed Central

    Lloyd, David R.; Kausch, Michael A.; Gancarz, Amy M.; Beyley, Linda J.; Richards, Jerry B.

    2012-01-01

    Background Light onset can be both a sensory reinforcer (SR) with intrinsic reinforcing properties, and a conditioned reinforcer (CR) which predicts a biologically important reinforcer. Stimulant drugs, such as methamphetamine (METH), may increase the reinforcing effectiveness of CRs by enhancing the predictive properties of the CR. In contrast, METH-induced increases in the reinforcing effectiveness of SRs, are mediated by the immediate sensory consequences of the light. Methods The effects of novelty (on SRs) and METH (on both CRs and SRs) were tested. Experiment 1: Rats were pre-exposed to 5 s light and water pairings presented according to a variable-time (VT) 2 min schedule or unpaired water and light presented according to independent, concurrent VT 2 min schedules. Experiment 2: Rats were pre-exposed to 5 s light presented according to a VT 2 min schedule, or no stimuli. In both experiments, the pre-exposure phase was followed by a test phase in which 5 s light onset was made response-contingent on a variable-interval (VI) 2 min schedule and the effects of METH (0.5 mg/kg) were determined. Results Novel light onset was a more effective reinforcer than familiar light onset. METH increased the absolute rate of responding without increasing the relative frequency of responding for both CRs and SRs. Conclusion Novelty plays a role in determining the reinforcing effectiveness of SRs. The results are consistent with the interpretation that METH-induced increases in reinforcer effectiveness of CRs and SRs may be mediated by immediate sensory consequences, rather than prediction. PMID:22814112

  10. Effects of sodium butyrate on methamphetamine-sensitized locomotor activity.

    PubMed

    Harkness, John H; Hitzemann, Robert J; Edmunds, Stephanie; Phillips, Tamara J

    2013-02-15

    Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, mice were treated repeatedly with MA (10 days of 2mg/kg MA) or saline (10 days), and then vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge and locomotor response was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, increased striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior.

  11. Response of limbic neurotensin systems to methamphetamine self-administration.

    PubMed

    Hanson, G R; Hoonakker, A J; Alburges, M E; McFadden, L M; Robson, C M; Frankel, P S

    2012-02-17

    Methamphetamine (METH) abuse is personally and socially devastating. Although effects of METH on dopamine (DA) systems likely contribute to its highly addictive nature, no medications are approved to treat METH dependence. Thus, we and others have studied the METH-induced responses of neurotensin (NT) systems. NT is associated with inhibitory feedback action on DA projections, and NT levels are elevated in both the nucleus accumbens and dorsal striatum after noncontingent treatment with high doses of METH. In the present study, we used a METH self-administration (SA) model (linked to lever pressing) to demonstrate that substitution of an NT agonist for METH, while not significantly affecting motor activity, dramatically reduced lever pressing but was not self-administered per se. We also found that nucleus accumbens NT levels were elevated via a D1 mechanism after five sessions in rats self-administering METH (SAM), with a lesser effect in corresponding yoked rats. Extended (15 daily sessions) exposure to METH SA manifested similar NT responses; however, more detailed analyses revealed (i) 15 days of METH SA significantly elevated NT levels in the nucleus accumbens shell and dorsal striatum, but not the nucleus accumbens core, with a lesser effect in the corresponding yoked METH rats; (ii) the elevation of NT in both the nucleus accumbens shell and dorsal striatum significantly correlated with the total amount of METH received in the self-administering, but not the corresponding yoked METH rats; and (iii) an NT agonist blocked, but an NT antagonist did not alter, lever-pressing behavior on day 15 in SAM rats. After 5 days in SAM animals, NT levels were also elevated in the ventral tegmental area, but not frontal cortex of rats self-administering METH.

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

    PubMed Central

    Borgmann, Kathleen; Ghorpade, Anuja

    2015-01-01

    As a popular psychostimulant, methamphetamine (METH) use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10 and 15% of human immunodeficiency virus-1 (HIV-1) patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND) through direct and indirect mechanisms. Repetitive METH use impedes adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression toward AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte numbers and activity, cytokine signaling, phagocytic function and infiltration through the blood brain barrier. Further, METH triggers the dopamine reward pathway and leads to impaired neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation, which modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress, and excitotoxicity. Pathologically, reactive gliosis is a hallmark of both HIV-1- and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus, this review highlights alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, with special emphasis on HAND-associated neuroinflammation. Importantly, this review carefully evaluates interventions targeting astrocytes in HAND and METH as potential novel therapeutic approaches. This comprehensive overview indicates, without a doubt, that during HIV-1 infection and METH abuse, a complex dialog between all neural cells is orchestrated through astrocyte regulated neuroinflammation. PMID:26579077

  13. Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

    PubMed Central

    Lominac, Kevin D.; McKenna, Courtney L.; Schwartz, Lisa M.; Ruiz, Paige N.; Wroten, Melissa G.; Miller, Bailey W.; Holloway, John J.; Travis, Katherine O.; Rajasekar, Ganesh; Maliniak, Dan; Thompson, Andrew B.; Urman, Lawrence E.; Phillips, Tamara J.; Szumlinski, Karen K.

    2014-01-01

    Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5–10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction. PMID:24847220

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

    PubMed Central

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

    2012-01-01

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

  15. Methamphetamine use and neuropsychiatric factors are associated with antiretroviral nonadherence

    PubMed Central

    Moore, David J.; Blackstone, Kaitlin; Woods, Steven Paul; Ellis, Ronald J.; Atkinson, J. Hampton; Heaton, Robert K.; Grant, Igor

    2012-01-01

    The present study assesses the impact of methamphetamine (METH) on antiretroviral (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors (i.e., major depressive disorder (MDD), Antisocial Personality Disorder (ASPD), and Attention Deficit Disorder (ADHD)) for ART nonadherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+/METH+; n = 67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+/METH−; n = 50). Ancillary analyses compared these groups with a small group of HIV+/METH+ persons with current METH abuse/dependence (HIV+/CU METH+; n = 8). Nonadherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH− participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART nonadherence (p’s<0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART nonadherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of nonadherence) than lifetime METH+ users and HIV+/METH-participants, and that neurocognitive impairment was associated with nonadherence (p’s<0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication nonadherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to

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

    PubMed Central

    Mayo, Leah M.; de Wit, Harriet

    2016-01-01

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

  17. Decreased dopamine activity predicts relapse in methamphetamine abusers

    SciTech Connect

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

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

    PubMed

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

    2015-12-01

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

  19. Methamphetamine Users in a Community-Based Drug Court: Does Gender Matter?

    ERIC Educational Resources Information Center

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

    2007-01-01

    This paper examines men and women methamphetamine (meth) users who participated in a community-based drug court. The treatment of female drug users is a particularly salient issue because of the concerns with relapse and recidivism. For the current study, we studied the impact of the drug court by gender on a group of high-risk/high-need meth…

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  1. 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…

  2. Role of the Ventral Tegmental Area in Methamphetamine Extinction: AMPA Receptor-Mediated Neuroplasticity

    ERIC Educational Resources Information Center

    Chen Han-Ting; Chen, Jin-Chung

    2015-01-01

    The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned…

  3. Involvement of Protein Phosphatases in the Destabilization of Methamphetamine-Associated Contextual Memory

    ERIC Educational Resources Information Center

    Yu, Yang-Jung; Huang, Chien-Hsuan; Chang, Chih-Hua; Gean, Po-Wu

    2016-01-01

    Destabilization refers to a memory that becomes unstable when reactivated and is susceptible to disruption by amnestic agents. Here we delineated the cellular mechanism underlying the destabilization of drug memory. Mice were conditioned with methamphetamine (MeAM) for 3 d, and drug memory was assessed with a conditioned place preference (CPP)…

  4. Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage.

    PubMed

    Fornai, F; Battaglia, G; Gesi, M; Orzi, F; Nicoletti, F; Ruggieri, S

    2001-04-13

    (R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson's disease.

  5. The Impact of Distinct Chemical Structures for the Development of a Methamphetamine Vaccine

    PubMed Central

    Moreno, Amira Y.; Mayorov, Alexander V.; Janda, Kim D.

    2011-01-01

    (+)-Methamphetamine (METH) use and addiction has grown at alarming rates over the past two decades, while no approved pharmacotherapy exists for its treatment. Immunopharmacotherapy has the potential to offer relief through producing highly specific antibodies that prevent drug penetration across the blood-brain barrier thus decreasing reinforcement of the behavior. Current immunotherapy efforts against methamphetamine have focused on a single hapten structure, namely linker attachment at the aromatic ring of the METH molecule. Hapten design is largely responsible for immune recognition as it affects presentation of the target antigen and thus the quality of the response. In the current paper we report the systematic generation of a series of haptens designed to target the most stable conformations of methamphetamine as determined by molecular modeling. Based on our previous studies with nicotine, we show that introduction of strategic molecular constrain is able to maximize immune recognition of the target structure as evidenced by higher antibody affinity. Vaccination of GIX+ mice with six unique METH immunoconjugates, resulted in high antibody titers for three particularly promising formulations (45–108 μg/mL, after second immunization) and high affinity (82, 130 and 169 nM for MH2, MH6 and MH7 hapten-based vaccines, respectively). These findings represent a unique approach to the design of new vaccines against methamphetamine abuse. PMID:21473576

  6. Methamphetamine Exposure, Iron Deficiency, and Implications for Cognitive-Communicative Function: A Case Study

    ERIC Educational Resources Information Center

    Goldberg, Lynette R.; Heiss, Cynthia J.; White, Letitia; Kaf, Wafaa A.; Becker, Alan; Schindler, Jessica B.; Dion, Nancy; Oswalt, Jill

    2010-01-01

    Methamphetamine (meth) exposure during fetal development has the potential to adversely affect the development of multiple organ systems. An interdisciplinary case study of a 4-year 11-month-old child born to a mother addicted to meth revealed significant cognitive and communicative delays. Possible meth-related consequences for these delays…

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

    PubMed Central

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

    2016-01-01

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

  8. Mediators of interpersonal violence and drug addiction severity among methamphetamine users in Cape Town, South Africa.

    PubMed

    Hobkirk, Andréa L; Watt, Melissa H; Green, Kimberly T; Beckham, Jean C; Skinner, Donald; Meade, Christina S

    2015-03-01

    South Africa has high rates of interpersonal violence and a rapidly growing methamphetamine epidemic. Previous research has linked experiences of interpersonal violence to higher rates of substance use, and identified mental health constructs as potential mediators of this association. The aim of this study was to examine the relationship between interpersonal violence and addiction severity among active methamphetamine users in Cape Town, South Africa, and to explore symptoms of posttraumatic stress disorder (PTSD) and substance use coping as mediators of this relationship. A community sample of 360 methamphetamine users was recruited through respondent driven sampling and surveyed on their experiences of violence, mental health, coping, and drug use and severity. A series of one-way ANOVAs were conducted to examine the relationship of self-reported interpersonal violence with drug addiction severity, and multiple mediation analyses were used to determine if PTSD symptoms and substance use coping mediated this relationship. The majority (87%) of the sample reported experiencing at least one instance of interpersonal violence in their lifetime, and the number of violent experiences was associated with increased drug addiction severity. PTSD and substance use coping were significant mediators of this association. Only the indirect effect of substance use coping remained significant for the female sample when the mediation model was conducted separately for men and women. The findings point to the need for integrated treatments that address drug use and PTSD for methamphetamine users in South Africa and highlight the importance of coping interventions for women.

  9. Examining Correlates of Methamphetamine and Other Drug Use in Pregnant American Indian Adolescents

    ERIC Educational Resources Information Center

    Barlow, Allison; Mullany, Britta C.; Neault, Nicole; Davis, Yvonne; Billy, Trudy; Hastings, Ranelda; Coho-Mescal, Valerie; Lake, Kristin; Powers, Julia; Clouse, Emily; Reid, Raymond; Walkup, John T.

    2010-01-01

    American Indian and Alaska Native (AI/AN) adolescents have high rates of pregnancy, as well as alcohol, marijuana, cocaine, and, increasingly, methamphetamine (meth) use. The progression of adolescent drug use to meth use could have devastating impacts on AI communities, particularly when youth are simultaneously at risk for teen childbearing. In…

  10. A Vodcasted, Cross-Disciplinary, Behavioral Neuroscience Laboratory Exercise Investigating the Effects of Methamphetamine on Aggression

    ERIC Educational Resources Information Center

    Shanks, Ryan A.; Southard, E. Megan; Tarnowski, Laura; Bruster, Matthew; Wingate, Stacia W.; Dalman, Nancy; Lloyd, Steven A.

    2011-01-01

    This article describes a laboratory experience utilizing videos to engage students in hypothesis-driven experimentation in behavioral neuroscience. It provides students with an opportunity to investigate the effects of chronic methamphetamine exposure on aggression in adult mice using a resident-intruder paradigm. Instructors and students only…

  11. Perceived Child Behavior Problems, Parenting Stress, and Maternal Depressive Symptoms among Prenatal Methamphetamine Users

    ERIC Educational Resources Information Center

    Liles, Brandi D.; Newman, Elana; LaGasse, Linda L.; Derauf, Chris; Shah, Rizwan; Smith, Lynne M.; Arria, Amelia M.; Huestis, Marilyn A.; Haning, William; Strauss, Arthur; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

    2012-01-01

    The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months.…

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION...-enforcement officials, health officials, individual physicians, parents, and others as well as from Food...

  13. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Amphetamine and methamphetamine inhalers regarded as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION...-enforcement officials, health officials, individual physicians, parents, and others as well as from Food...

  14. 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.

  15. Does Alexithymia Explain Variation in Cue-Elicited Craving Reported by Methamphetamine-Dependent Individuals?

    PubMed Central

    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.

    2011-01-01

    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. While 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. The present 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. PMID:22332856

  16. Mediators of interpersonal violence and drug addiction severity among methamphetamine users in Cape Town, South Africa

    PubMed Central

    Hobkirk, Andréa L.; Watt, Melissa H.; Green, Kimberly T.; Beckham, Jean C.; Skinner, Donald; Meade, Christina S.

    2014-01-01

    South Africa has high rates of interpersonal violence and a rapidly growing methamphetamine epidemic. Previous research has linked experiences of interpersonal violence to higher rates of substance use, and identified mental health constructs as potential mediators of this association. The aim of this study was to examine the relationship between interpersonal violence and addiction severity among active methamphetamine users in Cape Town, South Africa, and to explore symptoms of posttraumatic stress disorder (PTSD) and substance use coping as mediators of this relationship. A community sample of 360 methamphetamine users was recruited through respondent driven sampling and surveyed on their experiences of violence, mental health, coping, and drug use and severity. A series of one-way ANOVAs were conducted to examine the relationship of self-reported interpersonal violence with drug addiction severity, and multiple mediation analyses were used to determine if PTSD symptoms and substance use coping mediated this relationship. The majority (87%) of the sample reported experiencing at least one instance of interpersonal violence in their lifetime, and the number of violent experiences was associated with increased drug addiction severity. PTSD and substance use coping were significant mediators of this association. Only the indirect effect of substance use coping remained significant for the female sample when the mediation model was conducted separately for men and women. The findings point to the need for integrated treatments that address drug use and PTSD for methamphetamine users in South Africa and highlight the importance of coping interventions for women. PMID:25479528

  17. Characterization of Route Specific Impurities Found in Methamphetamine Synthesized by the Leuckart and Reductive Amination Methods

    PubMed Central

    2009-01-01

    Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of “route specific” impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the “target impurities” recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes. PMID:19637924

  18. Evaluation of characteristic deuterium distributions of ephedrines and methamphetamines by NMR spectroscopy for drug profiling.

    PubMed

    Matsumoto, Teruki; Urano, Yasuteru; Makino, Yukiko; Kikura-Hanajiri, Ruri; Kawahara, Nobuo; Goda, Yukihiro; Nagano, Tetsuo

    2008-02-15

    We have established a method for quantitative analysis of the deuterium contents (D/H) at the phenyl, methine, benzyl, N-methyl and methyl groups of l-ephedrine/HCl, d-pseudoephedrine/HCl and methamphetamine/HCl by 2H NMR spectroscopy. Comparison of the 5 position-specific D/H values of l-ephedrine/HCl and d-pseudoephedrine/HCl prepared by three methods (chemical synthesis, semichemical synthesis, and biosynthesis) showed that chemically synthesized ephedrines and semisynthetic ephedrines have highly specific distributions of deuterium at the methine position and at the benzyl position, compared with the other positions. The classification of several methamphetamine samples seized in Japan in terms of the D/H values at these two positions clearly showed that the methamphetamine samples had been synthesized from ephedrines extracted from Ephedra plants or semisynthetic ephedrines but not from synthetic ephedrine. This isotope ratio analysis method should be useful to trace the origins of seized methamphetamine in Southeast Asia.

  19. Methamphetamine Treatment Issues and Considerations among Men Who Have Sex with Men

    ERIC Educational Resources Information Center

    Goodrich, Kristopher M.

    2011-01-01

    Methamphetamine use is epidemic among men who have sex with men (MSM), but treatment has lagged for this group. The author reviews literature concerning use, individual effects of the drug, and treatment for MSM and discusses implications for counselor training, future practice, and research.

  20. The Crisis of Methamphetamine and Its Management: Preparation, Participation, and Prevention

    ERIC Educational Resources Information Center

    Cunniff, Judith; Cunniff, Daniel T.; Kay, Kenneth D.

    2008-01-01

    There is a drug crisis in the United States that is growing at an alarming rate. Its participants work in our businesses, government agencies, and schools. California leads the nation in drug use and until recently, Fresno County was the leader in methamphetamine production. This drug crisis is having a paralyzing effect causing loss of income,…

  1. Distributed Attentional Deficits in Chronic Methamphetamine Abusers: Evidence from the Attentional Network Task (ANT)

    ERIC Educational Resources Information Center

    Salo, Ruth; Gabay, Shai; Fassbender, Catherine; Henik, Avishai

    2011-01-01

    Objective: The goal of the present study was to examine distributed attentional functions in long-term but currently abstinent methamphetamine (MA) abusers using a task that measures attentional alertness, orienting, and conflict resolution. Methods: Thirty currently abstinent MA abusers (1 month-5 years) and 22 healthy non-substance using adults…

  2. A Meaningful Method: Research with Adolescent Girls Who Use Crystal Methamphetamine

    ERIC Educational Resources Information Center

    Newbury, Janet; Hoskins, Marie L.

    2008-01-01

    Embarking on a study in which we hope to gain a contextualized understanding of the experiences of adolescent girls who use crystal methamphetamines, it is crucial for us to select a research methodology congruent with our aims. In the current article, we share the theoretical basis and decision making process that has lead us to a multi-modal…

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

    PubMed Central

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

    2013-01-01

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

  4. Methamphetamine Self-Administration and Voluntary Exercise Have Opposing Effects on Medial Prefrontal Cortex Gliogenesis

    PubMed Central

    Mandyam, Chitra D.; Wee, Sunmee; Eisch, Amelia J.; Richardson, Heather N.; Koob, George F.

    2009-01-01

    Psychostimulant abuse produces deficits in prefrontal cortex (PFC) function, whereas physical activity improves PFC-dependent cognition and memory. The present study explored the vulnerability of medial PFC (mPFC) precursor proliferation and survival to methamphetamine self-administration and voluntary exercise, factors that may have opposing effects on mPFC plasticity to facilitate functional consequences. Intermittent 1 h access to methamphetamine (I-ShA) increased, but daily 1 and 6 h access decreased, proliferation and survival, with dose-dependent effects on mature cell phenotypes. All groups showed increased cell death. Voluntary exercise enhanced proliferation and survival but, in contrast to methamphetamine exposure, did not alter cell death or mature phenotypes. Furthermore, enhanced cell survival by I-ShA and voluntary exercise had profound effects on gliogenesis with differential regulation of oligodendrocytes versus astrocytes. In addition, new cells in the adult mPFC stain for the neuronal marker neuronal nuclear protein, although enhanced cell survival by I-ShA and voluntary exercise did not result in increased neurogenesis. Our findings demonstrate that mPFC gliogenesis is vulnerable to psychostimulant abuse and physical activity with distinct underlying mechanisms. The susceptibility of mPFC gliogenesis to even modest doses of methamphetamine could account for the pronounced pathology linked to psychostimulant abuse. PMID:17942739

  5. An Investigation of Bioecological Influences Associated with First Use of Methamphetamine in a Rural State

    ERIC Educational Resources Information Center

    Bowen, Anne; Moring, John; Williams, Mark; Hopper, Glenna; Daniel, Candice

    2012-01-01

    Purpose: Methamphetamine (MA) addiction is a significant problem in rural areas of the United States. Yet, little theoretically driven formative research has been conducted on the interactions of factors influencing initiation. The study was guided by Bronfenbrenner's bioecological model. Methods: Eighty-three MA users participated in an…