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    Educational attainment is not a good proxy for cognitive function in methamphetamine dependence. Dean Andy C,Hellemann Gerhard,Sugar Catherine A,London Edythe D Drug and alcohol dependence BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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. 10.1016/j.drugalcdep.2011.11.019
    Methamphetamine-associated cognitive decline is attenuated by neutralizing IL-1 signaling. Liśkiewicz Arkadiusz,Przybyła Marta,Park Minseon,Liśkiewicz Daniela,Nowacka-Chmielewska Marta,Małecki Andrzej,Barski Jarosław,Lewin-Kowalik Joanna,Toborek Michal Brain, behavior, and immunity Methamphetamine (METH) abusers are prone to develop a variety of comorbidities, including cognitive disabilities, and the immunological responses have been recognized as an important component involved in the toxicity of this drug. Cytokines are among the key mediators between systemic inflammatory status and tissue responses. One of these, interleukin 1 (IL-1), has been hypothesized to be involved in cognitive functions and also appears to play a pivotal role among inflammatory molecules. In the present study, we demonstrate that exposure of mice to METH markedly increased the protein level of IL-1β in hippocampal tissue. Additionally, METH administration induced a decline in spatial learning as determined by the Morris water maze test. We next evaluated the hypothesis that blocking IL-1β signaling can protect against METH-induced loss of cognitive functioning. The results indicated that METH-induced impaired spatial learning abilities were attenuated by co-administration of mouse IL-1 Trap, a dimeric fusion protein that incorporates the extracellular domains of both of the IL-1 receptor components required for IL-1 signaling (IL-1 receptor type 1 and IL-1 receptor accessory protein), linked to the Fc portion of murine IgG2a. This effect was associated with a decrease in hippocampal IL-1β level. The current study indicates for the first time that the loss of METH-related cognitive decline can be attenuated by neutralizing IL-1 signaling. Our findings suggest a potential new therapeutic pathway for treatment of altered cognitive abilities that occur in METH abusing individuals. 10.1016/j.bbi.2019.03.016
    Cognitive profile of ketamine-dependent patients compared with methamphetamine-dependent patients and healthy controls. Wang Liang-Jen,Chen Chih-Ken,Lin Shih-Ku,Chen Yi-Chih,Xu Ke,Huang Ming-Chyi Psychopharmacology BACKGROUND:Ketamine has emerged as a major substance of abuse worldwide and has been listed with methamphetamine (METH) as two of the most widely available illicit substances in Taiwan. Only a few studies have examined the long-term consequences of chronic and heavy ketamine abuse. We compared the cognitive function of ketamine-dependent patients with that of METH-dependent patients and healthy controls. METHODS:We recruited 165 participants (58 ketamine-dependent and 49 METH-dependent patients who sought treatment and 58 healthy controls) and evaluated them by using a cognitive test battery, the Brief Assessment of Cognition in Schizophrenia, with scores being estimated in reference to normative data in general population. RESULTS:The ketamine-dependent patients had significantly poorer performance than did the controls in many cognitive tests, including verbal memory, motor speed, verbal fluency, and attention and processing speed, and the battery as a whole. METH-dependent patients exhibited poorer function in motor speed, verbal fluency, and attention and processing speed. The ketamine group performed poorer than did METH group in the domains of verbal memory, working memory, and attention and processing speed and the composite battery scores. A previous experience of ketamine-induced psychotomimetic symptoms, using higher doses of ketamine, and longer abstinence appeared to be associated with performance in some tests; however, the significance disappeared after multiple comparison correction. CONCLUSIONS:The ketamine-dependent patients had impaired cognitive function, and METH-dependent patients exhibited intermediate performance between ketamine-dependent patients and healthy controls. Given the growing population of ketamine abusers, public education on the cognitive consequences should be provided. 10.1007/s00213-018-4910-z
    Pattern and related factors of cognitive impairment among chronic methamphetamine users. Wang Tong-Yu,Fan Teng-Teng,Bao Yan-Ping,Li Xiao-Dong,Liang Chun-Mei,Wang Ru-Jia,Ma Jun,Han Ying,Meng Shi-Qiu,Wu Ping,Shi Jie,Lu Lin The American journal on addictions BACKGROUND AND OBJECTIVES:Methamphetamine (MA) use is increasingly prevalent in East and Southeast Asia and commonly associated with cognitive impairment. The present study estimated the characteristics of cognitive impairment and explored the associated potential factors among chronic MA users. METHODS:The data were from the baseline visit of a longitudinal study among synthetic drug users. The baseline survey was conducted in detoxification and rehabilitation centers in Guangdong province, China, from September to December in 2013. A total of 528 participants were included in our analysis. Cognitive impairment was measured by the Montreal Cognitive Assessment (MoCA). Logistic regression was performed to explore the risk factors associated with cognitive impairment. RESULTS:Approximately 69.89% of the study participants exhibited cognitive impairment according to MoCA scores. Multiple logistic regression analyses indicated that older age (≥30 years old), a longer duration of MA use (>24 months), and a higher frequency of MA use (everyday) were associated with cognitive impairment, with adjusted odds ratios (ORs) of 1.58 (95% confidence interval [CI]: 1.07-2.34), 1.53 (95%CI: 1.01-2.31), and 1.55 (95%CI: 1.05-2.30), respectively. Methamphetamine users that had a higher level of education had a lower risk of cognitive impairment(OR = .59; 95%CI: .38-.93). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:Cognitive impairment occurred frequently among chronic MA users. The causal relationship between cognitive impairment and MA use needs to be ascertained in longitudinal studies in future work. Our study provides evidence for the development of intervention strategies for the prevention of MA use and associated cognitive impairment. (Am J Addict 2017;26:145-151). 10.1111/ajad.12505
    The neuroprotective effect of memantine on methamphetamine-induced cognitive deficits. Long Jian-Dong,Liu Yao,Jiao Dong-Liang,Wang Yu-Jun,Zan Gui-Ying,Ju Yun-Yue,Zhao Min,Liu Jing-Gen Behavioural brain research Repeated exposure to methamphetamine (METH) can cause severe neurotoxicity to the cortical neurons. In the present study, we investigated the effect of METH on cognitive function deficits, and determined the neuroprotective effects of memantine (MEM) on memory impairment induced by METH. The protein levels of Bcl-2 and cleaved caspase-3 in prefrontal cortex (PFC) were further examined to exploring the underlying mechanism. We found that repeated METH administration impaired long term (24h) memory retention without affecting short term (5min) memory retention. Co-administration of MEM with METH before training session significantly improved METH-induced cognitive function. METH significantly decreased expression level of Bcl-2 and increased expression level of cleaved caspase-3 in the PFC. The changes can be prevented by MEM pretreatment. Thus, these results demonstrated that MEM pretreatment reversed METH-induced changes of protein levels of apoptotic-related gene, and produced protective effects against METH-induced cognitive deficits, suggesting the effectiveness of MEM may be due to its anti-apoptotic activity. 10.1016/j.bbr.2017.01.042
    Psychological intervention with working memory training increases basal ganglia volume: A VBM study of inpatient treatment for methamphetamine use. Brooks S J,Burch K H,Maiorana S A,Cocolas E,Schioth H B,Nilsson E K,Kamaloodien K,Stein D J NeuroImage. Clinical BACKGROUND:Protracted methamphetamine (MA) use is associated with decreased control over drug craving and altered brain volume in the frontostriatal network. However, the nature of volumetric changes following a course of psychological intervention for MA use is not yet known. METHODS:66 males (41 MA patients, 25 healthy controls, HC) between the ages of 18-50 were recruited, the MA patients from new admissions to an in-patient drug rehabilitation centre and the HC via public advertisement, both in Cape Town, South Africa. 17 MA patients received 4 weeks of treatment as usual (TAU), and 24 MA patients completed TAU plus daily 30-minute cognitive training (CT) using an N-back working memory task. Magnetic resonance imaging (MRI) at baseline and 4-week follow-up was acquired and voxel-based morphometry (VBM) was used for analysis. RESULTS:TAU was associated with larger bilateral striatum (caudate/putamen) volume, whereas CT was associated with more widespread increases of the bilateral basal ganglia (incorporating the amygdala and hippocampus) and reduced bilateral cerebellum volume coinciding with improvements in impulsivity scores. CONCLUSIONS:While psychological intervention is associated with larger volume in mesolimbic reward regions, the utilisation of additional working memory training as an adjunct to treatment may further normalize frontostriatal structure and function. 10.1016/j.nicl.2016.08.019
    Cognitive deficit in methamphetamine users relative to childhood academic performance: link to cortical thickness. Dean Andy C,Morales Angelica M,Hellemann Gerhard,London Edythe D Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Individuals with cognitive problems may be predisposed to develop substance use disorders; therefore, differences in cognitive function between methamphetamine users and control participants may be attributable to premorbid factors rather than methamphetamine use. The goal of this study was to clarify the extent to which this is the case. Childhood academic transcripts were obtained for 37 methamphetamine-dependent adults and 41 control participants of similar educational level and premorbid IQ. Each participant completed a comprehensive cognitive battery and received a structural magnetic resonance imaging scan. Data from control participants and linear regression were used to develop a normative model to describe the relationship between childhood academic performance and scores on the cognitive battery. Using this model, cognitive performance of methamphetamine users was predicted from their premorbid academic scores. Results indicated that methamphetamine users' childhood grade point average was significantly lower than that of the control group (p < 0.05). Further, methamphetamine users' overall cognitive performance was lower than was predicted from their grade point average prior to methamphetamine use (p = 0.001), with specific deficits in attention/concentration and memory (ps < 0.01). Memory deficits were associated with lower whole-brain cortical thickness (p < 0.05). Thus, in addition to having an apparent premorbid weakness in cognition, methamphetamine users exhibit subsequent cognitive function that is significantly lower than premorbid estimates would predict. The results support the view that chronic methamphetamine use causes a decline in cognition and/or a failure to develop normative cognitive abilities, although aside from methamphetamine use per se, other drug use and unidentified factors likely contribute to the observed effects. 10.1038/s41386-018-0065-1
    Feasibility and acceptability of approach bias modification during methamphetamine withdrawal and related methamphetamine use outcomes. Manning Victoria,Garfield Joshua B B,Mroz Katherine,Campbell Samuel C,Piercy Hugh,Staiger Petra K,Lum Jarrad A G,Lubman Dan I,Verdejo-Garcia Antonio Journal of substance abuse treatment Approach bias modification (ApBM), a computerised cognitive training task which aims to reduce automatic, impulsive responding to drug-related cues, has been found to reduce alcohol consumption among individuals seeking treatment for their drinking. However, this approach has not been trialled in patients with methamphetamine use disorder (MUD), where altered impulsivity and reward processing are well-established. As such, this study aimed to examine the feasibility and acceptability of four consecutive days of ApBM training during a residential admission for methamphetamine withdrawal. Abstinence rates were examined 2-weeks and 3-months post-discharge. In terms of uptake, 52 of the 99 eligible patients approached agreed to participate and 47 of these 52 commenced training. Uptake and training completion rates (62%) were lower than those achieved in similar trials of ApBM for residential alcohol withdrawal, suggesting there are challenges to its delivery in this setting. This is likely due to the severity of acute methamphetamine withdrawal syndrome and associated behavioural characteristics. However, participants' ratings of the task and reports of post-session craving suggest acceptability was high. Abstinence rates were 61% at 2 weeks and 54% at 3-months, which compare favourably with the abstinence rates observed in a previous large treatment outcome study. The evidence of acceptability and apparent effectiveness suggest future trials of ApBM with MUD patients are warranted. However, ApBM may be more feasible in certain settings or among particular sub-groups where patients are more clinically stable and therefore more likely to complete the training (e.g., residential rehabilitation, after acute withdrawal has subsided). 10.1016/j.jsat.2019.07.008
    A Randomized Controlled Trial of Brief Cognitive Behavioral Therapy for Regular Methamphetamine Use in Methadone Treatment. Alammehrjerdi Zahra,Briggs Nancy E,Biglarian Akbar,Mokri Azarakhsh,Dolan Kate Journal of psychoactive drugs This study evaluated the efficacy of brief cognitive behavioral therapy (BCBT) for regular methamphetamine use among methadone-maintained women. A randomized controlled trial was conducted in four methadone treatment services. Eligible women were assigned to receive either BCBT or drug education. Five questionnaires were used to assess the research hypotheses at weeks 0, 4, and 12. Urinalysis was used to verify self-reported methamphetamine use at week 0. Urinalyses were used for those participants who reported abstinence from methamphetamine at weeks 4 and 12. Overall, 120 women were enrolled. Sixteen participants were lost to follow-up. Compared with the control group, the treatment group showed significant reductions in frequency of methamphetamine use ( < 0.001), severity of methamphetamine dependence ( < 0.001), and number of days of methamphetamine use ( < 0.001) at weeks 4 and 12. Significant improvements in readiness to change ( < 0.001), psychological well-being ( < 0.001), and social functioning ( = 0.001) were found in the treatment group at weeks 4 and 12. Nineteen urine specimens (31.66%) in the treatment group were negative for methamphetamine use at post-treatment and follow-up, while no change was found in the control group (0.00%). The study supported the efficacy of BCBT for methamphetamine use and associated harms. 10.1080/02791072.2019.1578445
    The impact of cognitive training in substance use disorder: the effect of working memory training on impulse control in methamphetamine users. Brooks Samantha J,Wiemerslage L,Burch K H,Maiorana S A,Cocolas E,Schiöth H B,Kamaloodien K,Stein D J Psychopharmacology OBJECTIVES:Impulsivity is a vulnerability trait for poor self-regulation in substance use disorder (SUD). Working memory (WM) training improves impulsivity and self-regulation in psychiatric disorders. Here we test WM training in methamphetamine use disorder (MUD). METHODS:There are 15 MUD patients receiving inpatient treatment as usual (TAU) and 20 who additionally completed WM cognitive training (CT) and 25 healthy controls (HC). MANCOVA repeated measures analyses examined changes in impulsivity and self-regulation at baseline and after 4 weeks. RESULTS:Post hoc t tests confirmed that at baseline, feelings of self-control were significantly lower in the MUD (t = 2.001, p = 0.05) and depression was higher (t = 4.980, p = 0.001), as was BIS total impulsivity (t = 5.370, p = 0.001) compared to the HC group. Total self-regulation score was higher in HC than MUD patients (t = 5.370, p = 0.001). CT had a 35% learning rate (R  = 0.3523, p < 0.05). Compared to follow-up TAU, follow-up CT group had higher self-reported mood scores (t = 2.784, p = 0.01) and higher compared to CT baseline (t = 2.386, p = 0.036). Feelings of self-control were higher in CT than TAU at follow-up (t = 2.736, p = 0.012) and also compared to CT baseline (t = 3.390, p = 0.006), lack of planning significantly improved in CT between baseline and follow-up (t = 2.219, p = 0.048), as did total impulsivity scores (t = 2.085, p = 0.048). Measures of self-regulation were improved in the CT group compared to TAU at follow-up, in total score (t = 2.442, p = 0.038), receiving score (t = 2.314, p = 0.029) and searching score (t = 2.362, p = 0.027). Implementing self-regulation was higher in the CT group compared to TAU (t = 2.373, p = 0.026). CONCLUSIONS:WM training may improve control of impulsivity and self-regulation in people with MUD. 10.1007/s00213-017-4597-6
    Testing the Efficacy of Combined Motivational Interviewing and Cognitive Behavioral Skills Training to Reduce Methamphetamine Use and Improve HIV Medication Adherence Among HIV-Positive Gay and Bisexual Men. Parsons Jeffrey T,John Steven A,Millar Brett M,Starks Tyrel J AIDS and behavior Prior research has identified subgroups of HIV-positive gay and bisexual men (GBM) based upon information, motivation, and behavioral skills (IMB) profiles related to HIV medication adherence and methamphetamine use. We conducted a randomized controlled trial of a combined motivational interview (MI) and cognitive behavioral therapy (CBT) intervention tailored specifically to the unique context of HIV-positive GBM, and tested whether IMB profiles moderated treatment effects. HIV-positive GBM (N = 210) were randomized to MI + CBT or an attention-matched education control. Both conditions resulted in reduced methamphetamine use, improved medication adherence (and higher CD4 and lower viral loads), and fewer acts of condomless anal sex at 3, 6, 9 and 12 months post-intervention. Furthermore, the MI + CBT condition achieved greater improvements in medication adherence for men who had greater barriers to change compared to similarly-classified men in the control condition, suggesting the importance of pre-intervention profiles for tailoring future interventions. 10.1007/s10461-018-2086-5