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Patients and psychotherapists often exhibit behavioral, psychological, and physiological similarity. Here, we test whether oxytocin-a neuropeptide that can enhance expressivity and social perception-influences time-lagged "linkage" of autonomic nervous system responses among participants and facilitators during group therapy. Physiological linkage estimates (n = 949) were created from ten cohorts, each with two facilitators (n = 5) and four to six participants (n = 48), over six weekly sessions of group therapy for methamphetamine use disorder. All participants of a cohort received oxytocin or placebo intranasally in a randomized double-blind procedure before each session. Cardiac interbeat intervals (IBI) were measured continuously during sessions to estimate physiological linkage, operationalized as one cohort-mate's IBI reactivity during one minute predicting another cohort-mate's IBI reactivity during the following minute. In oxytocin cohorts, participants and facilitators experienced significant physiological linkage to their cohort-mates (i.e., their physiological responses were predicted by the prior responses of their cohort-mates) and significantly more linkage than people in placebo cohorts. Both effects occurred during the first and second sessions but not later sessions. Results suggest that oxytocin may enhance psychosocial processes often associated with linkage-such as social engagement-in groups and highlight oxytocin's potential to improve group cohesion during group therapy.Clinical Trials Registration: NCT02881177, First published on 26/08/2016., (© 2021. The Author(s).)

Background: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations., Methods: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317)., Findings: The three real TBS groups had more craving decrease effect than the sham group (p<0.01). The changes of craving were positively correlated with the improvement of anxiety and withdrawal symptom. With the highest respondence rate, group C also had shorter respondence time than Group A (p = 0.03). Group C was effective in improve depression symptoms (p = 0.04) and withdrawal symptom (p = 0.02) compared with Group D. Besides, Group C was significant in improve sleep quality (p = 0.04) compared with Group A. Baseline depression scores and spatial working memory were positively predicting the intervention response., Interpretation: The rTMS paradigms involving vmPFC with cTBS are optimized protocols and well-tolerated for methamphetamine-dependent individuals, and they may have better efficacies compared with DLPFC iTBS. Emotion and cognitive function are rTMS treatment response predictors for methamphetamine-dependent patients., Funding: This work was supported by the National Key R&D Program of China (2017YFC1310400), National Natural Science Foundation of China (81,771,436, 81,801,319, 81,601,164), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ013), Qihang Project of Shanghai Mental Health Center (2019-QH-05), Shanghai Sailing Program (19YF1442100), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), and Shanghai Clinical Research Center for Mental Health (19MC1911100)., Competing Interests: Declaration of Competing interest All authors declared no competing interests for this work., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Methamphetamine is one of the most abused hard drugs in the Czech Republic. Its popularity is high not only in Eastern Bloc of Europe but is growing in other countries around the world, including the United States. In addition, methamphetamine abuse increases in drug addicts during pregnancy. Although research into the long-term effects of prenatal methamphetamine exposure has been ongoing for many years, the exact mechanism of action and factors that may influence the effect of this drug are still not fully understood. There have been many studies that investigated the effects of addictive substances on the behavior and cognitive function of individuals during adolescence. Some studies have shown prenatal or perinatal influences, e.g. drugs, stress, hypoxia, and malnutrition, can affect drug sensitivity or drug-seeking behavior in adulthood. However, when these factors are most impactful, i.e. prenatal vs. perinatal, and which stages of the prenatal and perinatal periods are the most sensitive to these factors is not yet clear. Our laboratory specializes in research on the effects of drugs (especially methamphetamine) on rat mothers and their offspring during postnatal development, adolescence, and adulthood. This review summarizes our past results on the long-term effects of methamphetamine on the mother and her offspring, its mechanism of action, the role of maternal care, the possible emergence of long-term sensitization, and the critical neurodevelopmental periods for methamphetamine exposure.

Chronic heavy methamphetamine use likely causes dopaminergic neurotoxicity, which is commonly thought to result in cognitive control deficits. Both of these alterations may persist even after the use is discontinued, but tend to (partly) improve with increasing duration of abstinence. While several studies have demonstrated that the reinstatement of comparatively normal dopaminergic signaling may take months, if not years, the amelioration of cognitive deficits has predominantly been investigated in much shorter intervals of several weeks to less than half a year. Against this background, we set out to investigate the effects on prolonged abstinence in n = 27 abstinent former methamphetamine users in a cross-sectional design using behavioral and neurophysiological measures of cognitive control. Our behavioral results suggest that former users struggled to identify and adapt to different degrees of cognitive control requirements, which made their behavioral performance less expedient than that of healthy controls. On the neurophysiological level, this was reflected by reduced modulations of the N2-N450 amplitude in response to high vs. low cognitive control requirements. Yet, those effects could only be observed in methamphetamine users who had been abstinent for a relatively short time (mean 9.9; max. 18 months), but not in former users who had been abstinent two years or longer. While this finding alone does not allow for causal inferences, it suggests that the amelioration of control deficits may take longer than what is commonly investigated (1-6 months). Hence, some of the statements about permanent/irreversible dopamine-dependent executive dysfunctions in former methamphetamine users should be interpreted with caution., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Abuse of psychostimulants, including methamphetamine (MA), has been linked to heightened impulsivity. While previous research has demonstrated differences in impulsivity between MA users and non-substance users, less is known about variability in impulsivity within MA users and whether the severity of MA use related problems predicts impulsivity within individuals who regularly use MA. This study aims to elucidate the relationship between impulsivity and MA use severity., Method: Non-treatment seeking individuals who reported regular MA use (n = 177) completed an impulsivity battery comprising self-report and behavioral measures. A structural equation modeling (SEM) approach was used to test the relationship between the MA use related problem severity and measures of impulsivity., Results: The final SEM model of impulsivity and MA use related problems (CFI = 0.897, RMSEA = 0.059, S-B scaled χ 2 [260,n = 103] = 406.86) revealed that greater MA use severity was associated with greater self-reported impulsiveness, but no relationship was found between MA use severity and behavioral measures of impulsivity., Conclusions: The current findings extend previous research by providing additional evidence that MA use is associated with increased self-reported impulsivity and highlights the importance of evaluating impulsivity as a multidimensional construct., (Copyright © 2018. Published by Elsevier B.V.)

Background: Methamphetamine abuse has been linked to an increased risk of Parkinson's disease., Objective: The objective of this study was to investigate structural abnormality of the substantia nigra in past methamphetamine users using transcranial sonography., Methods: In a cross-sectional, observational study, echogenicity of the substantia nigra was assessed in 59 past methamphetamine users and 59 matched controls. The frequencies of an abnormal spatial extension of the substantia nigra as well as the average sizes of left and right substantia nigra were evaluated., Results: The average echogenic size of the substantia nigra was larger in methamphetamine users (0.22 ± 0.06 cm 2 ) when compared with controls (0.17 ± 0.05 cm 2 , P < .001). Furthermore, the frequency of enlarged, echogenic substantia nigra was increased in methamphetamine users (42% vs 12% in controls, P < .001). Partial correlation analysis revealed an association of echogenic substantia nigra size with estimated total lifetime intake of methamphetamine (r 55  = 0.395, P = .002)., Conclusions: Current data link methamphetamine abuse in humans to injury of substantia nigra neurons and an increased risk of Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Amphetamine-type stimulants (ATS) use is increasingly prevalent in Malaysia, including among individuals who also use opioids. We evaluated cognitive functioning profiles among individuals with co-occurring opioid and ATS dependence and their lifetime patterns of drug use. Participants (N = 50) enrolling in a clinical trial of buprenorphine/naloxone treatment with or without atomoxetine completed the Raven's Standard Progressive Matrices, Rey-Osterrieth Complex Figure Test, Digit Span, Trail Making and Symbol Digit Substitution tasks. Multidimensional scaling and a K-means cluster analyses were conducted to classify participants into lower versus higher cognitive performance groups. Subsequently, analyses of variance procedures were conducted to evaluate between group differences on drug use history and demographics. Two clusters of individuals with distinct profiles of cognitive performance were identified. The age of ATS use initiation, controlling for the overall duration of drug use, was significantly earlier in the lower than in the higher cognitive performance cluster: 20.9 (95% CI: 18.0-23.8) versus 25.2 (95% CI: 22.4-28.0, p = 0.038). While adverse effects of ATS use on cognitive functioning can be particularly pronounced with younger age, potentially related to greater vulnerability of the developing brain to stimulant and/or neurotoxic effects of these drugs, the current study findings cannot preclude lowered cognitive performance before initiation of ATS use.

Objective: To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship., Study Design: The multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5-year follow-up, 290 children with complete Child Behavior Checklist data and an early adversity index score were available for analysis (n = 146 exposed)., Results: PME was significantly associated with an increased early adversity index score (P < .001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P < .05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant., Conclusions: Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Developing efficacious medications to treat methamphetamine dependence is a global challenge in public health. Topiramate (TPM) is undergoing evaluation for this indication. The molecular mechanisms underlying its effects are largely unknown. Examining the effects of TPM on genome-wide gene expression in methamphetamine addicts is a clinically and scientifically important component of understanding its therapeutic profile., Methods: In this double-blind, placebo-controlled clinical trial, 140 individuals who met the DSM-IV criteria for methamphetamine dependence were randomized to receive either TPM or placebo, of whom 99 consented to participate in our genome-wide expression study. The RNA samples were collected from whole blood for 50 TPM- and 49 placebo-treated participants at three time points: baseline and the ends of weeks 8 and 12. Genome-wide expression profiles and pathways of the two groups were compared for the responders and non-responders at Weeks 8 and 12. To minimize individual variations, expression of all examined genes at Weeks 8 and 12 were normalized to the values at baseline prior to identification of differentially expressed genes and pathways., Results: At the single-gene level, we identified 1054, 502, 204, and 404 genes at nominal P values < 0.01 in the responders vs. non-responders at Weeks 8 and 12 for the TPM and placebo groups, respectively. Among them, expression of 159, 38, 2, and 21 genes was still significantly different after Bonferroni corrections for multiple testing. Many of these genes, such as GRINA, PRKACA, PRKCI, SNAP23, and TRAK2, which are involved in glutamate receptor and GABA receptor signaling, are direct targets for TPM. In contrast, no TPM drug targets were identified in the 38 significant genes for the Week 8 placebo group. Pathway analyses based on nominally significant genes revealed 27 enriched pathways shared by the Weeks 8 and 12 TPM groups. These pathways are involved in relevant physiological functions such as neuronal function/synaptic plasticity, signal transduction, cardiovascular function, and inflammation/immune function., Conclusion: Topiramate treatment of methamphetamine addicts significantly modulates the expression of genes involved in multiple biological processes underlying addiction behavior and other physiological functions.

Repeated administration of psychostimulant drugs, such as amphetamine, induces an enhanced behavioral response to subsequent drug challenge. This behavioral sensitization is proposed to model the increased drug craving observed in human psychostimulant abusers. Current thinking is that the ventral tegmental area, but not the nucleus accumbens, plays a critical role in the development of behavioral sensitization. Here, we report that the concomitant blockade of glutamatergic and nicotinic ionotropic receptors in the core of the nucleus accumbens blocks the development of behavioral sensitization to amphetamine and further abolishes the increase in extracellular dopamine release induced by amphetamine in the nucleus accumbens. These findings demonstrate that the development of behavioral sensitization to amphetamine depends, in addition to the well-known role of the ventral tegmental area, on glutamatergic and nicotinic-dependent mechanisms in the core of the nucleus accumbens and further indicate that the dopaminergic mesolimbic pathway must be viewed as a single coordinated system of critical importance in the development of behavioral sensitization to psychostimulant drugs., (© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.)

We have shown that a single "binge" dose of methamphetamine (Meth) in mice has long-lasting effects on open-field behavior dependent on mouse strain and age. Here we further investigated the impact of genotype and age on tyrosine hydroxylase (TH) loss and dopamine (DA) metabolism due to a high binge dose of Meth (4 × 5 mg/kg × 2 h × 2 days). Administration of high dose Meth or saline (Sal) to adolescent (PND 40) and adult (PND 80) C57BL/6 (B6), DBA/2 (DBA), and 129S6SvEv/Tac (129) mice was followed by a 1mg/kg Meth or Sal (control) challenge 40 days later. Striatal and prefrontal cortex tissues were collected 1h following the challenge. Meth-pretreated adolescent B6 and DBA mice exhibited losses in striatal DA concentrations; DBA adolescents also showed losses in striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and increased DA turnover. Pre-exposed B6 and 129 adults demonstrated significant decreases in striatal DA, DOPAC, and increased DA turnover; DBA adults showed significant losses in striatal DA and increased DA turnover. 129 and DBA adults exhibited increases and decreases, respectively, in prefrontal cortex DA. Adult pretreated B6 mice produced significant losses in striatal TH. The results again show age and genotype dependent differences in Meth-induced DA alterations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Methamphetamine abuse has reached epidemic proportions in the United States. The repetitive use of methamphetamine causes massive and sustained elevations in central monoamines. These elevations, particularly in dopamine, can cause changes in the function of the central nervous system that can manifest as a variety of neurologic disorders. This article focuses on these disorders, such as neurocognitive disorders and mental illness, including drug-induced psychosis; motor disorders, including the possible risk of Parkinson's disease, the development of choreoathetoid movements, and punding; and changes in the physical appearance of the methamphetamine users, including dental caries., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Several studies suggest a link between stimulant abuse and attention-deficit hyperactivity disorder (ADHD) symptoms (e.g., inattention and hyperactivity). To further assess the nature of this relationship, the present study examined the association between subclinical symptoms of inattention and hyperactivity and the behavioral effects of d-amphetamine., Methods: Participants were classified into a High- (n = 8) or Low-Score (n = 9) group based on their responses on a rating scale that assessed inattention and hyperactivity symptoms., Results: The participants did not differ across the High-Score and Low-Score groups in their ability to discriminate d-amphetamine. The participants in the High-Score group were significantly more sensitive to the positive participant-rated effects of d-amphetamine (e.g., Good Effects, Like Drug), but less sensitive to drug-induced increases in blood pressure and heart rate., Conclusion: The selective increase in positive subjective effects of d-amphetamine suggests that individuals with subclinical inattention and hyperactivity symptoms may have increased vulnerability to stimulant abuse.

3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative with psychostimulant properties. This substance is widely used around the world by young adults in recreational settings. One of the most remarkable characteristic of ecstasy users is the concurrent consumption of several other drugs of abuse including psychostimulants, alcohol, tobacco, LSD, cannabis and opioids. This poly-drug pattern of use is now prompting research towards understanding how the combination of MDMA with cannabis and opioids could affect neuropsychobiological processes related to addiction. As with other drugs of abuse, behavioural evidence has been presented supporting the role of the endocannabinoid system as a modulator of the rewarding/reinforcing properties of MDMA. On the other hand, the neurochemical substrate for the complex interactions between the endocannabinoid system and MDMA is poorly understood. MDMA also modulates the activity of the dynorphinergic and enkephalinergic systems in several brain structures related to addiction, as it has been shown for other psychostimulants. The work regarding the contribution of micro- and delta-opioid receptors in the rewarding effects of MDMA shows differential results in pharmacological studies in rats, with respect to studies using knock-out mice. The present review describes the behavioural and neurochemical interactions between MDMA, cannabinoids and opioids with respect to addiction processes.

Attention-deficit/hyperactivity disorder (ADHD) in adults is often associated with a comorbid substance use disorder (SUD). To date, no treatment algorithms are available. The question of whether the administration of methylphenidate (MPH) is justified in the treatment of adult patients with ADHD and comorbid SUD still remains unclear. While animal studies indicate an addictive potential of intravenous application of the drug, controlled oral treatment with MPH does not seem to carry the potential for abuse in humans. It remains controversial whether MPH treatment of ADHD during childhood protects against the development of SUD during adulthood. Although data remain inconsistent, a small number of studies and our own clinical observations of ADHD patients with SUD treated with MPH support a reduction not only of ADHD-related symptoms, but also of craving and substance abuse. The treatment of the adult ADHD with comorbid SUD with MPH should be conducted after a risk-benefit assessment, taking into consideration the abused substances, the motivation to abstinence and the quality of the physician-patient relationship; it should be evaluated critically, monitored closely and accompanied by treatment of the SUD and specific psychotherapy/psychoeducation.

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

The role of the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in the expression of behavioural locomotor sensitization to amphetamine (Amph) has been poorly studied. In the present study, we investigated how lidocaine infused in the mPFC or BLA modulated motor responses to acute and repeated (sensitization) Amph administration. We showed that reversible blockade of mPFC or BLA by lidocaine increased both locomotor and rearing responses to acute Amph, but blocked the expression of behavioural sensitization to Amph. These findings indicate that under free-lidocaine conditions repeated administration of Amph would produce a shift of mPFC and BLA motor function from an inhibitory to a facilitatory role in response to Amph. We propose that this phenomenon may be of major critical importance in the development of drug dependence.

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

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.

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.

Drug addiction represents a pathological form of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry. The aberrant behavioral phenotypes can be assessed by an animal model of drug-induced behavioral sensitization, which is characterized by an initiation stage that is formed in the ventral tegmental area and a behavioral expression stage determined mainly in the nucleus accumbens. Numerous studies during past decades demonstrate that the mesocorticolimbic dopamine pathway plays an essential role in the development of behavioral sensitization. Moreover, a series of cellular signaling pathways and gene expression determine the severity of addictive behaviors. In addition to the well-characterized dopamine D1 receptor-mediated cAMP/protein kinase A up-regulation in the nucleus accumbens, recent reports indicate the cellular mediator dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and transcription regulator DeltaFosB are associated with the accumbal PKA pathway to modulate the development of behavioral sensitization. The finding of cAMP-independent and dopamine D2 receptor-mediated Akt/GSK3 in activation in the nucleus accumbens of behaviorally sensitized animals implies that a signal cascade down-stream of both dopamine D1 and D2 receptors comprises the mainstay of the addiction network. This review outlines the cellular pathways that have been demonstrated to participate in psychostimulant addiction, focused particularly in the nucleus accumbens.

Numerous medical sequelae associated with illicit drug use have been reported. Nevertheless, there has been scarce documentation of the effects of these drugs on the eyes. Drug-induced ocular symptoms include decreased visual acuity, disturbances in perception, and even flashbacks. Methamphetamine (METH) is a highly addictive drug whose abuse has spread worldwide during the past two decades. METH abuse is associated with many adverse psychiatric and medical consequences including strokes and psychosis. METH-induced ophthalmic complications are rarely discussed but include retinal vasculitis, episcleritis, panophthalmitis, endophthalmitis, scleritis, retinopathy, corneal ulceration, and transient visual losses. Because the drug has shown a marked increase in the prevalence of its use amongst pregnant women, there has also been an increase of drug-induced complications in fetuses and newborn babies. These complications need to be further detailed and studied. Herein, the authors report on the ocular complications associated with METH abuse. They also discuss some potential mechanisms for the toxic effects of the drug on that system.

Unlabelled: Crystal Meth: is a synthesis drug whose consumption developed with the beginning of the year 2000 in Europe. Crystal can be swallowed, crunched, smoked, injected or inserted by rectal way. Required effects: "crystal" removes tiredness, brings a feeling of power and of self-control, makes trustful, sexy and merry. Clinical effects: by its sympathomimetic action-like, "crystal" causes hypertension and tachycardia. It crosses the placenta and and is excreted in the mother's milk. It brings to a dependence similar to that of cocaine., Complications: "crystal" can generate cardiopulmonary complications, can reveal cognitive and psychological disorders. It leads the consumers to have not protected and repeated sexual relations., Conclusion: in France, the consumption of "crystal" remains marginal. Plan 2007-2011 of assumption of responsibility and prevention of the addictions integrates the elements such as the prevention to fight against the extension of this drug.

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

Since 2000 researchers have reported a decline in the administration of attention-deficit/hyperactivity disorder (ADHD) medications given by school nurses, although no decline has been noted in the incidence of ADHD in school-age populations. Government data for the same period show reduced levels of methylphenidate abuse as measured by its involvement in hospital emergency department (ED) admissions. Offsetting this, however, is an increase in the involvement of amphetamine-dextroamphetamine in hospital ED admissions for the same period. Because ADHD medications are often administered in the school setting, a survey of school nurses was undertaken to identify factors related to the administration as well as to the diversion, theft, and misuse of ADHD medications. Of 311 school nurses responding, 295 (95%) reported a significant or moderate decline between 2002 and 2004 in the need for school-based administration of ADHD medications. Respondents also reported reductions in diversion, theft, and misuse of ADHD drugs.

The epidemic of methamphetamine dependence is spreading eastward across the United States. Unlike the gender ratio associated with most other drugs of abuse, the proportion of woman methamphetamine users is nearly equal to men. This review will describe reasons why women begin use of methamphetamine, especially those that differ from the usual reasons for initiating drug use. The characteristics of women users at entry into treatment also differ from those of men, especially in regard to employment, psychological symptoms, and history of abuse and violence in their lives. Finally, the review will address treatment issues and options that can be responsive to the distinctive needs of women dependent on methamphetamine.

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

Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.

Methamphetamine use is an increasingly serious public health problem in California and other parts of the country. Despite sensationalistic media attention, however, very little is known about users of this clandestinely consumed drug. Employing methods known as Rapid Assessment and Response, the authors describe the epidemiology and public health implications of methamphetamine use in California's Central Valley, with a focus on Sacramento, which many social indicators suggest has been more severely affected by methamphetamine than any city in the nation. Data sources for this report include interviews with drug users, statistical reports, epidemiologic studies, and local informed expert opinion. In their social demography, methamphetamine users in the Central Valley are in marked contrast to those of coastal cities such as Seattle and San Francisco, being largely heterosexual, and of mixed racial/ethnic heritage. Three-quarters or more initiate their use of the drug while still in their teens, with more than a quarter beginning use before the age of 15. Many of these rapidly gravitate to regular use, and continue using well into their thirties. Methamphetamine users are at much higher risk of infection with HIV than opiate users, particularly if they inject. Partly because methamphetamine enhances libido, users of the drug typically also have many more sexual partners. Not surprisingly, data indicate that methamphetamine users are more likely than heroin users to be HIV-infected. Methamphetamine appears to be less of a street drug than heroin, complicating efforts at street outreach. However, because it is typically used in social settings, a social or diffusion approach to HIV prevention might be particularly promising.

Animal studies have shown that nicotine and psychostimulant drugs (amphetamine and cocaine) share the property of inducing long-lasting behavioral and neurochemical sensitization, which is thought to contribute to their addictive properties. Neuroplasticity subserving learning and memory mechanisms is considered to be involved in psychostimulant-induced sensitization and addiction behavior. Because nicotinic receptors in the brain play a role in the storage of drug-related information underlying reinforcement learning, we evaluated the possibility that activation of central nicotinic receptors may underlie psychostimulant-induced sensitization. Repeated exposure of rats to nicotine profoundly enhanced the psychomotor effects of nicotine and amphetamine 3 weeks after nicotine pretreatment. Moreover, the nicotinic receptor antagonist mecamylamine completely blocked the induction, but not the long-term expression, of behavioral sensitization to amphetamine in amphetamine-pretreated rats. Mecamylamine also prevented the development of cocaine-induced behavioral sensitization. Behavioral sensitization induced by nicotine, amphetamine, or cocaine was associated with an increase in the electrically evoked release of [(3)H]dopamine from nucleus accumbens slices. Coadministration of mecamylamine during pretreatment with nicotine, amphetamine, or cocaine prevented the development of this long-term hyperreactivity of nucleus accumbens dopamine neurons. Similarly, the high-affinity non-alpha7 subtype nicotinic receptor antagonist dihydro-beta-erythroidine prevented the development of amphetamine-induced behavioral and neurochemical sensitization. These data indicate that nicotinic receptor activation (by endogenously released acetylcholine) is a common denominator initiating neuroplasticity involved in the development of amphetamine, as well as cocaine-induced sensitization.

Understanding the association between attention deficit hyperactivity disorder (ADHD) and substance abuse, specifically methamphetamine (MA) abuse, is challenging, partly because little is known about the specific constellation of cognitive impairments produced by MA. The present investigation serves to address this relationship by comparing the cognitive performance of MA abusers with ADHD symptomatology (n = 28) and MA abusers without ADHD symptomatology (n = 41) on tests of attention, memory and general intellectual functioning, executive functioning, problem solving, verbal fluency, and abstract thinking. Both MA samples had deficiencies in measures of memory and learning function, psychomotor speed and abstract thinking when compared to a control group (n = 40). Additional deficits were noted on tasks involving executive functioning, attention, and general intellectual functioning in MA abusers with ADHD symptomatology. The preliminary data suggests that executive function deficits and some of the symptoms associated with long-term MA use may be due to the fact that a large proportion of MA addicts had ADHD symptomatology as children.

Who are methamphetamine (MA) users and what are the circumstances that surround their drug use? This article provides a foundation for future ethnographic studies and collaborative clinician-researcher assessments of MA use by describing use ecology and drug use motivation for 260 MA users admitted to treatment at public Los Angeles County facilities in 1996. Use ecology data include MA varieties and street names, first introductions to use, drug use histories, access, selling and manufacturing, routes of administration, unwanted results of use, and participants' use behavior in the year before the 1996 treatment. Use motivation data describe clients using MA as a substitute for other stimulants; to cope with mental distress; to stay awake; to enhance sexual experience; and to lose weight. Qualitative case studies illustrate the findings and demonstrate the complex inter-relations of society, culture, psyche and soma shaping MA use over time.

Methamphetamine use has clearly reached epidemic proportions in large parts of the western and midwestern US. Because of the regional specificity of methamphetamine use, there is speculation that it may be a temporary problem and not a long-term public health problem. Unfortunately there are a number of factors that suggest that significant methamphetamine problems may persist or even expand. For this reason, it is important that federal law enforcement, prevention, research and treatment agencies prepare strategies to address the likelihood of this persisting problem. This article reviews the issues concerning the future of the methamphetamine problem in the US and provides some recommendations for setting priorities to address the problem.

Consumption of the illicit drugs amphetamine, ecstasy and cocaine is increasing in Denmark and Europe leading to an increasing number of intoxications with these drugs. Abroad, several deaths after ingestion of a few doses of the drugs have been reported. Amphetamine, ecstasy and cocaine increase the amount of dopamine, norephedrine and serotonine in the nervous system, resulting in CNS stimulation and a general sympathomimetic stimulation. Symptoms to be treated originate mainly from the CNS and the cardiovascular system, and present as tachycardia, hypertension and seizures, later hypotension and coma. Hyperpyrexia, rhabdomyolysis and affections of the kidneys, lung and liver function are also often seen. Hyperpyrexia is an important marker of poor prognosis, and must be handled aggressively. A review of the literature concerning the optimal treatment based on pharmacological and diagnostic considerations is given in the article.

Patients with methamphetamine toxicity are presenting in greater numbers each year to emergency departments (ED) in the US. These patients are frequently agitated, violent, and often require physical and chemical restraint. The incidence and risk of rhabdomyolysis in this subpopulation is unknown. We conducted a 5-year retrospective review of all ED patients who received the final diagnosis of rhabdomyolysis. Patients with toxicology screens positive for methamphetamine were identified, and demographics, laboratory results, resource utilization, disposition, and outcome were compared to the remaining patients. Of the total 367 patients identified, 166 (43%) were toxicology positive for methamphetamine. Methamphetamine patients differed significantly from nonmethamphetamine patients with regard to demographics and hospital utilization. Methamphetamine patients had significantly higher mean initial creatine phosphokinase (CK), 12,439 U/L versus 5,678 U/L (P = 0.02), and lower mean peak CK, 16,827 U/L versus 19,426 U/L (P = 0.03). The development of acute renal failure was not significantly different between the 2 groups. There were 16 total deaths in the study population, 11 from concomitant infection/sepsis. An association between methamphetamine abuse and rhabdomyolysis may exist, and CK should be measured in the ED as a screen for potential muscle injury in this subpopulation. Patients with rhabdomyolysis with an unclear cause should be screened for methamphetamine or other illicit drugs.