Methamphetamine-dependent Patients Research Articles

Efficacy of group reality therapy versus desipramine pharmacotherapy in drug craving and relapse of methamphetamine-dependent patients in yazd

Aims: In this comparative study, we aimed to investigate the effectiveness of group reality therapy versus desipramine pharmacotherapy in reducing the craving and relapse of methamphetamine-dependent patients. Methods: This semi-experimental research was conducted using a control group and two experimental groups of reality therapy and desipramine pharmacotherapy. The statistical population of this study included all methamphetamine-dependent patients under methadone treatment who were referred to the health clinics of Yazd city, Iran. We selected 30 patients using convenience sampling and then categorized them randomly into three groups of reality therapy, desipramine pharmacotherapy, and control. In the pre-test stage, the risk questionnaire was administered to evaluate the stimulants. The first experimental group attended 10 reality therapy sessions once a weak and was assessed immediately after the treatment. The data were analyzed using the covariance analysis. Results: The findings showed no significant difference between the total mean score of the reality therapy and desipramine pharmacotherapy groups (F= 3.289, P= 0.087). Hence, these two interventions did not affect attenuating craving to use the drugs. To check the homogeneity presumptions of the covariance matrix and variances of the two groups, the Box (6.241) and Levine (0.250) tests were applied, respectively. The results about the experimental groups (Reality therapy and Desipramine group) compared to the control group were meaningful. Conclusion: There was no significant difference between reality therapy and desipramine pharmacotherapy groups in reducing the craving to use the drugs. The scope of changes showed that craving for drug consumption reduced in reality therapy (51.0) and desipramine pharmacotherapy (36.0) groups.

Effects of Atomoxetine for Cognitive Function in Methamphetamine-dependent Patients: A Randomized Controlled Trial

Background: A substantial body of evidence indicates that methamphetamine abuse can lead to persistent and severe cognitive dysfunction. Preclinical studies and early pilot clinical investigations suggested that atomoxetine, a cognitive enhancer, may improve cognitive dysfunction. The present study evaluated whether atomoxetine would affect cognitive dysfunction in methamphetamine-dependent patients. Methods: Participants with methamphetamine dependence (N=86) under Methadone Maintenance Therapy (MMT) were enrolled in a double-blind, placebo-controlled, randomized clinical trial. This investigation was performed on 86 subjects to consume either 40 mg/day atomoxetine (n=45) or placebo (n=41) for 8 weeks. Between January 2016 and June 2017, volunteers were selected from methamphetamine abusers in MMT centers in Kashan City, Iran. They completed the Cognitive Abilities Questionnaire at the first and each monthly visit to assess the cognitive functions. The collected data were analyzed using the Independent Samples t-test, Mann Whitney U test, and Chi-square in SPSS software. Results: This study revealed that atomoxetine treatment improved some cognitive dysfunctions in methamphetamine users, including memory, inhibitory control, selective attention, decisionmaking, planning, sustained attention, and cognitive flexibility in methamphetamine users (P<0.05); however, social cognition improvement was less than others (P=0.107). There were only mild adverse effects in the placebo and atomoxetine groups. Conclusion: The obtained findings indicated the efficacy of atomoxetine for improving cognitive dysfunction in methamphetamine users and suggest the potential effectiveness of atomoxetine for treating them.

Effects of Atomoxetine for Cognitive Function in Methamphetamine-dependent Patients: A Randomized Controlled Trial

Background: A substantial body of evidence indicates that methamphetamine abuse can lead to persistent and severe cognitive dysfunction. Preclinical studies and early pilot clinical investigations suggested that atomoxetine, a cognitive enhancer, may improve cognitive dysfunction. The present study evaluated whether atomoxetine would affect cognitive dysfunction in methamphetamine-dependent patients. Methods: Participants with methamphetamine dependence (N=86) under Methadone Maintenance Therapy (MMT) were enrolled in a double-blind, placebo-controlled, randomized clinical trial. This investigation was performed on 86 subjects to consume either 40 mg/day atomoxetine (n=45) or placebo (n=41) for 8 weeks. Between January 2016 and June 2017, volunteers were selected from methamphetamine abusers in MMT centers in Kashan City, Iran. They completed the Cognitive Abilities Questionnaire at the first and each monthly visit to assess the cognitive functions. The collected data were analyzed using the Independent Samples t-test, Mann Whitney U test, and Chi-square in SPSS software. Results: This study revealed that atomoxetine treatment improved some cognitive dysfunctions in methamphetamine users, including memory, inhibitory control, selective attention, decisionmaking, planning, sustained attention, and cognitive flexibility in methamphetamine users (P<0.05); however, social cognition improvement was less than others (P=0.107). There were only mild adverse effects in the placebo and atomoxetine groups. Conclusion: The obtained findings indicated the efficacy of atomoxetine for improving cognitive dysfunction in metham

Analysis of Mental State of Patients after Drug Addiction and Withdrawal Guided by PETCT Image Based on Optimized Image Fusion Algorithm

Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) studies have shown that drug-dependent patients are activated in different addictive brain areas under the stimulation of relevant environmental cues, which in turn leads to craving and relapse. This study uses magnetic resonance spectroscopy to measure brain temperature to explore the brain temperature changes in different addictive brain regions of heroin and methamphetamine addicts in a short-term withdrawal state and to explore whether the quantitative index of brain temperature change can be used as a diagnostic drug Methods. The subjects were scanned by resting-state MRI spectroscopy first and then subjected to MRI spectroscopy scanning under visual stimulation. The subjects were required to watch the heroin/meth-related clue pictures carefully during visual stimulation. The measured chemical shift value of N-acetyl-aspartic acid (NAA) is substituted into the brain temperature calculation formula T = 37 + 100 to obtain the brain temperature before and after visual stimulation. In addition, the anxiety and depression states of heroin and methamphetamine-dependent patients were evaluated. Results. There was no statistically significant change in the brain temperature of the prefrontal cortex before and after visual stimulation in heroin and methamphetamine-dependent subjects; compared with the normal group, there was no change in prefrontal cortex brain temperature before and after visual stimulation in heroin and methamphetamine-dependent subjects. Statistical Significance. The changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients were not statistically significant; compared with the normal group, there was no statistically significant difference in the changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients. Conclusion. This study initially found that the visual cues related to heroin and methamphetamine were not enough to cause significant changes in the brain temperature of the prefrontal cortex.

Association Between Alexithymia, Social Support, and Duration of Methamphetamine Use Among Male Methamphetamine-Dependent Patients.

Introduction: China has 1.18 million methamphetamine abusers. Among the illegal drugs in China, methamphetamine has the highest abuse rate. Although previous studies have indicated a positive relationship between alexithymia and declining social support, the incidence of alexithymia, the total duration of methamphetamine dependence, social support, and the relationships between them among methamphetamine-dependent patients in the Chinese population have been rarely reported.Methods: A total of 113 methamphetamine-dependent patients (all male, mean age 30.45 ± 3.81 years) were enrolled in this cross-sectional study. General demographic data were collected. Alexithymia and social support were measured by Toronto Alexithymia Scale and Social Support Rating Scale.Results: Duration of methamphetamine use among Chinese male methamphetamine-dependent patients in compulsory detoxification was 8.01 ± 3.80 years on average, 23% (26/113) methamphetamine-dependent patients were considered to have alexithymia personality traits. Compared with short-duration methamphetamine-dependent patients (≤8 years), long-duration methamphetamine-dependent patients (> 8 years) were characterized by older age, higher incidence of alexithymia, less subjective social support and support availability, and greater difficulty in identifying feelings. The results of correlation analysis and multiple linear regression analysis indicated that the total duration of methamphetamine use was positively correlated with difficulty in identifying feelings, but negatively correlated with subjective social support.Conclusions: This study provides support for an association between the duration of methamphetamine use and difficulty in identifying feelings or subjective social support. Although the causality is still unclear, this finding should be considered in the psychotherapy of methamphetamine rehabilitation.

Effects of cytidine-5′-diphosphate choline on gray matter volumes in methamphetamine-dependent patients: A randomized, double-blind, placebo-controlled study

BackgroundCytidine-5′-diphosphate choline (CDP-choline) has been suggested to exert neuroprotective and neuroreparative effects and may be beneficial for patients with stimulant dependence. This randomized, double-blind, placebo-controlled study in methamphetamine (MA) dependence investigated effects of CDP-choline on the brain structures and their associations with craving and MA use. MethodsMA users (n = 44) were randomized to receive 2 g/day of CDP-choline (n = 22) or placebo (n = 22) for 8 weeks. Patients underwent brain magnetic resonance imaging (MRI) at baseline and 8-week follow-up. Healthy individuals (n = 27) were also examined using brain MRI at the same interval. Voxel-based morphometry analysis was conducted to examine changes in gray matter (GM) volumes and their associations with craving and MA use. ResultsCraving for MA was significantly reduced after the 8 week-treatment with CDP-choline (p = 0.01), but not with the placebo treatment (p = 0.10). There was no significant difference in the total number of MA-negative urine samples between the two groups (p = 0.19). With CDP-choline treatment, GM volumes in the left middle frontal gyrus (p = 0.001), right hippocampus (p = 0.009), and left precuneus (p = 0.001) were significantly increased compared to the placebo and control groups. Increased GM volumes in the left middle frontal gyrus with CDP-choline treatment were associated with reduced craving for MA (Spearman's ρ = −0.56, p = 0.03). In addition, the right hippocampal volume increases were positively associated with the total number of MA-negative urine results in the CDP-choline group (Spearman's ρ = 0.67, p = 0.006). ConclusionOur findings suggest that CDP-choline may increase GM volumes of MA-dependent patients, which may be related to decreases in MA use and craving.

The Higher Parietal Cortical Thickness in Abstinent Methamphetamine Patients Is Correlated With Functional Connectivity and Age of First Usage.

AimThis study aimed to explore the changes of cortical thickness in abstinent methamphetamine (MA) patients compared with healthy controls.Materials and MethodsThree-tesla structural and functional magnetic resonance imaging (MRI) was obtained from 38 abstinent methamphetamine-dependent (AMD) patients and 32 demographically equivalent healthy controls. The cortical thickness was assessed using FreeSurfer software. General linear model was used to get brain regions with significant different cortical thickness between groups (p < 0.05, Monte Carlo simulation corrected). The mean cortical thickness value and functional connectivity with all other brain regions was extracted from those significant regions. Moreover, correlation coefficients were calculated in the AMD group to assess the relations between the mean cortical thickness, functional connectivity and age when they first took MA and the duration of both MA use and abstinence.ResultsThe AMD group showed significant cortical thickness increase in one cluster located in the parietal cortex, including right posterior central gyrus, supramarginal gyrus, and superior parietal lobule. In addition, cortical thickness values of those regions were all significant and negatively correlated with the age when patients first used MA. The cortical thickness of right posterior gyrus were positively correlated with its functional connectivities with left middle frontal gyrus and both left and right medial orbitofrontal gyrus.ConclusionThe higher cortical thickness in the parietal cortex of the AMD group is in agreement with findings in related studies of increased glucose metabolism and gray matter volume. Importantly, the negative correlation between parietal cortical thickness and age of first MA suggested that adolescent brains are more vulnerable to MA’s neurotoxic effect.

Effects of 12-week aerobic exercise on cue-induced drug craving in methamphetamine-dependent patients and the moderation effect of working memory

ObjectiveTo explore the effect of 12-week aerobic exercise of varying intensity on cue-induced drug craving in methamphetamine (MA)-dependent patients and how this effect may be moderated or mediated by changes in cognitive function. MethodFifty-seven MA-dependent patients were randomly divided into three groups. Two exercise groups were engaged in a 12-week exercise program that involved three 30-min sessions per week of moderate- or high-intensity aerobic exercise on a cycle ergometer. The control group maintained daily life in a drug rehabilitation center for 12 weeks. Inhibitory control, working memory, and cue-induced drug craving were assessed before and after the intervention via Stroop task, 2-back task and visual analogue scale, respectively. ResultsA 12-week program of high-, but not medium-, intensity aerobic exercise significantly reduced cue-induced drug craving and improved working memory performance, while did not improve inhibitory control. Multiple linear regressions revealed that the effects of aerobic exercise on cue-induced drug craving were moderated by working memory. ConclusionsHigh-intensity aerobic exercise could be used to reduce cue-induced drug cravings of MA-dependent patients while also providing benefits in working memory. For patients with improved working memory, 12-week aerobic exercise can significantly reduce cue-induced drug craving, and the higher the exercise intensity, the greater the decrease in craving. These results suggest that appropriate high-intensity exercise would be a positive tool to promote drug rehabilitation for patients without any physical or medical conditions, and the improvement of working memory is important for exercise-induced effects.

Cabergoline in Treatment of Methamphetamine-Dependent Patients and Its Effect on Serum Level of Glial Cell-Derived Neurotrophic Factor: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Methamphetamine use disorder is an important public health problem, especially in the younger generation, and associated with various psychiatric, cognitive, social, economic, and legal issues. Cabergoline, a drug with dopaminergic properties and long half-life, has been considered for the treatment of stimulant dependence. The systemic use of cabergoline has been shown to increase glial cell-derived neurotrophic factor (GDNF) expression. Objective: In this study, we investigated the effects of cabergoline on the serum level of GDNF and its effect on abstaining from methamphetamine in individuals treated for methamphetamine use disorder. Method: Sixty male subjects with methamphetamine use disorder were randomly assigned to 2 groups receiving cabergoline and placebo, respectively. During a 12-week follow-up, we compared the serum level of GDNF, urine test results for methamphetamine use, and depression scale between the 2 groups. Results: We found that serum GDNF was lower in subjects who used methamphetamine than healthy subjects (p < 0.0001). However, the serum level of GDNF was not associated with cabergoline use. The rising number of cases testing positive in the placebo group showed a trend resulting in no significant difference between cases testing positive and negative (p = 0.585) at the end of week 12. In the verum group, however, the significantly high number of cases who tested negative – sober – for substances observed in early stages (weeks 7–8) continued to remain significantly higher till the end of the study (p = 0.043), resembling an association between treatment with cabergoline and remaining sober. Although reduced during treatment, recovery from depression was not associated with cabergoline treatment. Conclusion: The findings of this study confirmed the effect of cabergoline in reducing methamphetamine use. However, a serum level of the GDNF increase, as seen in animal studies, was not associated with cabergoline treatment of human subjects. This study was registered at the Iranian Registry of Clinical Trials (TRN:IRCT2015050422077N1, October 06, 2015, https://en.irct.ir/trial/19134).

Associations Between Childhood Trauma and the Age of First-Time Drug Use in Methamphetamine-Dependent Patients.

Childhood trauma is related to substance use disorder; however, few studies have examined the relationship between childhood trauma and the age at which the drug was first used. The aim of this study was to investigate the relationship between childhood trauma and the age of first-time drug use among methamphetamine-dependent patients. Moreover, we analyzed the characteristics of adverse family environment associated with severe childhood trauma and the risk factors for starting drugs in minors. A baseline interview was conducted with 110 participants who were in detoxification, including demographic information, past substance use, and age of first-time drug use. The participants' childhood trauma experience before 18 years of age was evaluated using the simplified version of the Childhood Trauma Questionnaire (CTQ-SF). The Chinese version of the Family Environment Scale (FES-CV) was used to assess the family environment of methamphetamine-dependent patients. Among 110 non-injecting methamphetamine-dependent patients, nearly half (n = 48, 43.6%) had moderate and severe childhood trauma. Correlation analysis showed that the age of first-time drug use negatively correlated with emotional abuse (r = −0.32, p < 0.01) and physical abuse (r = −0.27, p < 0.01). The age of first-time drug use negatively correlated with conflict (r = −0.20, p < 0.05) and independence (r = −0.22, p < 0.05) of family environment, but positively correlated with intellectual-cultural orientation (r = 0.28, p < 0.01). Additionally, childhood trauma factors significantly correlated with many indexes of family environment, especially cohesion (r = −0.45, p < 0.01), conflict (r = 0.49, p < 0.01), and independence (r = 0.33, p < 0.01). Additionally, the regression model showed that when emotional abuse increased by one point, the age of first-time drug use was 0.69 years earlier. These findings suggest that a detrimental family environment can aggravate childhood trauma, and the experience of childhood emotional or physical abuse may be an effective predictor of early drug use among methamphetamine-dependent patients.

Prognostic plasma exosomal microRNA biomarkers in patients with substance use disorders presenting comorbid with anxiety and depression

Psychiatric disorders such as anxiety and depression precipitated by substance use occurred during both use and withdrawal. Exosomes play significant roles in biological functions and regulate numerous physiological and pathological processes in various diseases, in particular substance use disorders (SUDs) and other psychiatric disorders. To better understand the role of exosomal miRNAs in the pathology of symptoms of anxiety and depression in patients with SUDs, we first isolated circulating exosomes from heroin-dependent patients (HDPs) and methamphetamine-dependent patients (MDPs) and identified exosomal miRNAs that were differentially expressed between patients and healthy controls (HCs). Furthermore, the correlations between exosomal DE-miRNAs and symptoms of anxiety and depression which were measured using Hamilton-Anxiety (HAM-A)/Hamilton-Depression (HAM-D) Rating Scales in the participants. Notably, the expression level of exosomal hsa-miR-16-5p, hsa-miR-129-5p, hsa-miR-363-3p, and hsa-miR-92a-3p showed significantly negative correlations with HAM-A scores in both HDPs and MDPs. But all of the 4 DE-miRNAs lost significant correlations with HAM-D scores in HDPs. Functional annotation analyses showed that the target genes of the DE-miRNAs were mainly enriched for “synapse”, “cell adhesion”, “focal adhesion” and “MHC class II protein complex”. Our study suggests that a set of circulating exosomal miRNAs were associated with anxiety and depression in SUD patients and may have clinical utility as diagnostic and prognostic biomarkers.

The exploration of optimized protocol for repetitive transcranial magnetic stimulation in the treatment of methamphetamine use disorder: A randomized sham-controlled study.

BackgroundThe 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.MethodsSeventy-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).FindingsThe 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.InterpretationThe 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.FundingThis 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).

Inflammation but not programmed cell death is activated in methamphetamine-dependent patients: Relevance to the brain function

Animal studies have shown that methamphetamine (MA) induces neurodegeneration through programmed cell death, however, the effects of MA on human brain and the extent of induced neural degeneration is not well understood. Given that the dose and duration of MA administration differ in animals and humans, we evaluated MA effects on active users considering brain damage mechanisms. Nineteen active MA-dependent patients and 18 healthy controls performed the color-word Stroop task, during fMRI and their blood samples were collected. Human enzyme-linked immunosorbent assays (ELISA) and quantitative PCR were applied to measure circulating proteins and miRNAs involved in various programmed cell death pathways (apoptosis, necroptosis, and autophagy), brain damage and neuroinflammation. Results showed the performance deficit in color-word Stroop task in MA abusers as well as higher activations of the right inferior and middle temporal gyri detected by fMRI. Structural MRI revealed increased white matter volume in MA-dependent patients in the superior and medial frontal gyri, and left/right middle temporal gyrus. Molecular analyses detected no significant differences in the plasma levels of the studied proteins and miRNAs of MA-dependent patients and controls except the higher levels of MBP, S100B, and TNFα in MA abusers. Results showed that MA induced physiological and structural changes accompanied by inflammation and release of damage-associated molecules in MA-dependent patients.

Neurotransmitter system aberrations in patients with drug addiction.

Drug dependence may affect the neurotransmitter system levels in the human body. This study recruited 113 healthy control subjects, 118 heroin-dependent patients and 118 methamphetamine-dependent patients and examined the serum 5-HT, dopamine, glutamate and norepinephrine levels in the 349 volunteers. ELISA assays demonstrated that the serum 5-HT levels were significantly reduced in the drug-dependent patients, whereas the serum dopamine and glutamate levels were both significantly increased in the drug-dependent patients when compared with control subjects. In contrast, the norepinephrine levels did not exhibit a significant difference between the drug-dependent and control subjects. We also used qRT-PCR to analyze the transcriptional expression levels of 5-HT1A, 5-HT1B, dopmaine-D1 and dopamine-D2 receptors in the blood of drug-dependent patients and controls, and the results show that only 5-HT1B receptor levels were dysfunctional in the heroin abusers. In addition, our results suggest that serum 5-HT, dopamine, and glutamate levels had the potential to differ between drug abusers and controls, and combining those three potential biomarkers provided an accurate means to differentiate between the drug-dependent and control subjects. Taken together, our study reveals a differential profile of neurotransmitters in the heroin-dependent patients and methamphetamine-dependent patients, and this revelation may contribute to understanding the pathophysiology of drug addiction.

Evaluation of stress-coping strategies and their association with relapse rate in people with methamphetamine use disorder: an analytical study

ABSTRACT The growing prevalence of methamphetamine use and the relevant relapse have become major issues across the world presently. Thus, the current study aims to investigate the stress-coping strategies and their relationship with the relapse rate among people with methamphetamine use disorder. The statistical population in the present analytical research comprises all methamphetamine-dependent patients referred to Farabi Hospital in Kermanshah in 2018, out of which 172 are included in the study by an accessible sampling method. The research instruments include Cassidy-Long Problem-Solving Styles Questionnaire (PSS) and Time to Relapse Questionnaire (TRQ). Data analysis shows that 51 (29.1%) subjects benefit from effective stress-coping strategies, while 124 (70.9%) apply ineffective stress-coping strategies. Further, the relapse rate among the people who used effective stress-coping strategies is (P < .05). The mean of the total relapse risk score is higher among the women and the methamphetamine-dependent patients with withdrawal history (P < .05). The present research findings reveal that the relapse rate among individuals who decide to use ineffective stress-coping strategies is higher. Therefore, it is recommended to consider stress-coping strategies applied by methamphetamine users in order to be able to diminish their relapse rate.

The effects of aerobic exercise on working memory in methamphetamine-dependent patients: Evidence from combined fNIRS and ERP

ObjectiveTo explore the effect of aerobic exercise on working memory according to exercise intensity in patients with methamphetamine (MA) dependence. DesignTwelve-week randomized controlled trial. MethodForty-five MA-dependent patients were divided randomly into three groups participating in 12-week moderate- and high-intensity aerobic exercise interventions and no intervention (control), respectively. Working memory performance was assessed using a 2-back task, and a combined functional near-infrared spectral imaging–event-related potential measure was used to identify spatial and temporal components of the neurofunctional underpinnings of this performance. ResultsHigh-intensity exercise significantly enhanced the discernment aspect of working memory. It also decreased N1 and P2 amplitudes, and increased neural activity in the left dorsolateral prefrontal cortex. ConclusionsThe findings of this study suggest that high-intensity aerobic exercise can enhance working memory and neural activity in MA-dependent patients, and thus that it may serve as an effective therapeutic tool for these patients.

γ-aminobutyric acid and glutamate/glutamine alterations of the left prefrontal cortex in individuals with methamphetamine use disorder: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study.

BackgroundGABAergic and glutamatergic neurotransmitter systems are critical in the pathophysiology of addiction and represent potential targets for repetitive transcranial magnetic stimulation (rTMS). This study aims to investigate changes in γ-aminobutyric acid (GABA) levels, the combined resonance of glutamate and glutamine (Glx) in the left dorsolateral prefrontal cortex (DLPFC), and cognitive function of patients with methamphetamine dependence following rTMS intervention, using proton magnetic resonance spectroscopy (1H MRS).MethodsFifty methamphetamine-dependent patients were randomized to a 4-week course of active or sham rTMS, with 1H MRS measurement of DLPFC GABA and Glx levels relative to n-acetyl-aspartate (NAA) and craving and cognitive function measured at baseline and post-intervention.ResultsWe observed significant reductions of GABA/NAA concentration in the active group and Glx/NAA concentration in the group receiving sham rTMS. There was a significant association between changes in GABA concentration and problem solving/error monitoring.ConclusionsThe effect of rTMS on cognitive function in individuals with methamphetamine dependence may be related to changes in GABA levels in the prefrontal cortex, and warrants further investigation.

Frontocingulate Dysfunction Is Associated with Depression and Decreased Serum PON1 in Methamphetamine-Dependent Patients.

IntroductionStudies have been reported that frequent use of methamphetamine (MA) is associated with brain function impairment, mood disorders and excessive free radical production accompanied by the decreased level of the antioxidant response elements, but no study investigated their correlations simultaneously. In the current study, the correlation of brain function, depression and anxiety levels, and the serum levels of PON1 (an antioxidant) in MA-dependent patients were investigated.MethodsNineteen active MA abusers and 18 control subjects performed color-word Stroop task during fMRI and the state of their depression, anxiety, and stress were measured by the Depression, Anxiety and Stress Scale-21 Items (DASS-21) questionnaire. Their blood samples were collected to measure the level of PON1 by the human enzyme-linked immunosorbent assay (ELISA) kit and its correlation with the measured variables was studied.ResultsAnalysis of fMRI findings showed frontocingulate dysfunction in Stroop effect condition, including left anterior cingulate cortex, paracingulate gyrus, superior frontal gyrus, and frontal pole in MA-dependent patients, which was associated with a higher level of depression and decreased level of serum PON1 in these patients.DiscussionThe results of the current study showed that MA-dependency is associated with frontocingulate dysfunction, decreased serum PON1 concentration, and increased depression/anxiety, which is worth to be more studied to elucidate their roles in the pathophysiology of MA addiction.

Effects of Exercise on Depression, Anxiety, Cognitive Control, Craving, Physical Fitness and Quality of Life in Methamphetamine-Dependent Patients.

Methamphetamine (MA) abuse results in a variety of harmful changes in mood states and cognitive function, together with declined physical health and quality of life. Recent studies highlighted the therapeutic potential of physical exercise on MA addiction. Physical exercise improves emotional state and general health conditions, enhances cognitive function, reduces relapse rate, and facilitates abstinence, thereby improves the overall quality of life of the drug users. This review summarizes the present situation of physical exercise on MA-dependent patients with both animal and clinical population results.

Decreased GABA concentrations in left prefrontal cortex of methamphetamine dependent patients: A proton magnetic resonance spectroscopy study

Increasing evidence suggested the dorsolateral prefrontal cortex (DLPFC) is implicated in the pathogenesis of methamphetamine use disorder. Metabolites changes of DLPFC may mediate the progression of addiction. We used proton magnetic resonance spectroscopy (1H-MRS) to examine the changes of metabolites in the left DLPFC in individuals with methamphetamine dependence compared to healthy controls. Fifty patients and twenty age-matched healthy controls participated in this study. The 1H MRS data were automatically fit with linear combination model for quantification of metabolite levels of γ-aminobutyric acid (GABA), glutamate + glutamine (Glx) and other metabolites across groups. The GABA and Glx levels were calculated with the unsuppressed water signal as reference. Methamphetamine users showed reduced GABA and GABA/Glx in left DLPFC than healthy controls. Furthermore, the concentration of GSH, GPC, Ins, NAA, GPC + PCh, NAA + NAAG, Cr + PCr were lower in individuals with methamphetamine dependence compared with controls. The patients group's relative GABA and Glx metabolite concentrations were significantly correlated with age and duration of withdrawal. Our preliminary findings provide the first report of abnormal levels of GABA in left DLPFC of patients with methamphetamine use disorder, indicating that dysregulation of the GABAergic neurotransmitter system may be an important neurobiological mechanism in the pathogenesis of methamphetamine dependence.