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The poor oral health condition of individuals who abuse methamphetamine (MA) is well known. The roles of the oral and fecal microbiomes in addiction and nervous system diseases have been the focus of many studies. However, changes in the microbiota composition of MA users have not been reported. This was addressed in the present study in 20 MA users and 14 sex-matched healthy subjects. Saliva samples were collected and high-throughput 16S rRNA sequencing and bioinformatic analysis were performed to evaluate oral microbiome profiles. The results showed that species richness was significantly lower in the MA group than in the control group. Bacterial taxa that are known to be related to oral diseases such as Negativicutes, Veillonellaceae, Veillonella, and Selenomonadales had higher relative abundance in the MA group than in the control group, and the relative abundance of Prevotella melaninogenica—a putative etiologic agent of periodontal disease—was also higher. Avoiding MA use and improving oral hygiene practices over a short term (i.e., during hospitalization for 2 weeks) did not alter the oral microbiota composition of MA users. Although the causal relationship between changes in oral microbiome profile and MA abuse remains to be determined, our results suggest that oral disease prevention and treatment strategies are important for MA users. [ABSTRACT FROM AUTHOR]

Background: There is an increasing demand of evidence-based treatment options for methamphetamine users, but research in this field is limited. This study therefore evaluates the efficacy of two residential treatment programs for methamphetamine users.Method: A total of 108 patients with a history of methamphetamine abuse from two inpatient rehabilitation centers were studied for psychiatric symptoms, craving, psychosocial resources, and cognitive functioning at the start and end of therapy. Patients from one center ("amphetamine type stimulant group") received conventional group therapy plus an additional 10 h of group therapy focusing on stimulant use. Patients from the other center ("treatment as usual") received conventional group therapy only. Predictors of drop-out were estimated.Results: A drop-out rate of 40.7% was observed without a significant difference between both centers. Patients remained significantly longer in treatment as usual compared to amphetamine type stimulant treatment. Irrespective of treatment program, craving and psychiatric symptoms significantly decreased while psychosocial resources, processing speed, and cognitive flexibility improved over time. Other cognitive measures yielded mixed results. History of injection drug use was a significant predictor for treatment drop-out.Conclusions: Existing treatments are effective in reducing craving and psychiatric symptoms. Additional stimulant specific groups do not appear to influence treatment completion and secondary outcome measures. Institutions should therefore offer treatment for methamphetamine users, even if they do not provide a therapy content focusing on methamphetamine. History of injection drug use should receive attention in treatment to prevent drop-out. Changes in cognitive functioning need to be further explored. [ABSTRACT FROM AUTHOR]

Methamphetamine abuse has become a serious public health problem. However, effective treatment for methamphetamine addiction remains elusive, especially considering its high rate of relapse after treatment. A conditioned stimulus (CS) memory retrieval–extinction procedure has been demonstrated to decrease reinstatement of cocaine, heroin, and alcohol seeking in rats, and to reduce cue-induced cravings in heroin and nicotine addicts. The goal of the present study is to explore the effect of the CS memory retrieval–extinction procedure on methamphetamine seeking in rats and the underlying mechanisms. We found that daily retrieval of methamphetamine-associated memories 1 h before extinction sessions decreased subsequent drug priming-induced reinstatement, spontaneous recovery, and renewal of methamphetamine seeking. We also found that retrieval of methamphetamine-associated memories induced neuronal activation in the basolateral amygdala (BLA), while presenting extinction within the time window of reconsolidation abolished the neuronal activation in BLA. These results indicate that the CS memory retrieval–extinction procedure could prevent reconsolidation of methamphetamine memory traces in BLA and subsequent methamphetamine craving and relapse. [ABSTRACT FROM AUTHOR]

Objective: Naltrexone has been shown to attenuate craving and the subjective effects of methamphetamine. Although naltrexone has modulatory effects on neural activity at dopaminergic synapses, the effect on striatal connectivity is unclear. As methamphetamine use is associated with greater resting-state functional connectivity (RSFC) in the dopaminergic system, we examined whether extended-release naltrexone (XR-NTX) can normalize striatal connectivity and whether changes in RSFC are associated with changes in craving and methamphetamine use.Methods: Thirty-seven participants in or seeking treatment for methamphetamine use disorder took part in this clinical trial at a university-based research clinic between May 2013 and March 2015 (Clinicaltrials.gov NCT01822132). Participants were randomized by a random number generator to a single four-week injection of XR-NTX or placebo. Functional magnetic resonance imaging (fMRI) and self-reported measures of craving and methamphetamine use were conducted before and after double-blinded randomization.Findings: There was a significant reduction in methamphetamine use in the naltrexone group and a significant treatment-by-time interaction on RSFC between the ventral striatum, amygdala, hippocampus, and midbrain. Connectivity was significantly reduced over time in participants randomized to naltrexone but unchanged in those randomized to placebo (p < 0.05, whole-brain corrected). Interactions between treatment and changes in connectivity show that significant reductions in connectivity were associated with reductions in methamphetamine use.Conclusions: Neurobiological deficits associated with methamphetamine use may undermine the efficacy of pharmacotherapies that directly target the dopamine reward system. Naltrexone, via antagonism of indirect mu-opioid effects on dopamine neurons, may attenuate reward system connectivity and aid in methamphetamine use treatment. [ABSTRACT FROM AUTHOR]

Background: HIV-positive persons who use stimulants such as methamphetamine experience greater difficulties in navigating the HIV care continuum. In the era of HIV treatment as prevention (TasP), little is known about the prevalence and correlates of success along the HIV care continuum among people who use stimulants.Setting: San Francisco, California USA METHODS: Cross-sectional study that enrolled 129 HIV-positive men who have sex with men (MSM) from 2013 through 2017 who had biologically confirmed, recent methamphetamine use. Multivariable logistic regressions were built to identify correlates of success across the HIV care continuum.Results: Although two-thirds (87/129) of participants had undetectable HIV viral load (<40 copies/mL), only one-in-four (32/129) reported taking at least 90% of their antiretroviral therapy (ART). Those who were homeless in the past year (adjusted odds ratio [aOR] = 0.20; 95% CI = 0.06-0.65) had 80% lower odds of being undetectable and adherent to ART. Substance use disorder treatment was associated with 77% lower odds of being engaged in HIV care (aOR = 0.23; 95% CI = 0.06-0.84) but also close to 3-fold greater odds of being adherent to ART (aOR = 2.91; 95% CI = 1.12-7.60).Conclusion: Despite the fact that many HIV-positive, methamphetamine-using MSM are able to achieve undetectable viral load in this sample, difficulties with ART adherence threaten to undermine the clinical and public health benefits of TasP. Expanded efforts to boost the effectiveness of TasP in this population should focus on meeting the unique needs of homeless individuals, optimizing ART adherence, and facilitating the integration of HIV care with substance use disorder treatment. [ABSTRACT FROM AUTHOR]

Abstract Relapse following a prolonged period of drug cessation is a key barrier in the treatment of methamphetamine (METH) addiction, for which pharmacological treatment exhibits little efficacy. Previous studies have suggested that this process involves alterations in levels of serotonin (5-HT) in the brain. Although the 5-HT 1F receptor has been implicated in the reward pathway, its physiological functions remain unknown. In the present study, we examined the effect of the 5-HT 1F agonist LY 344864 on the reinstatement of METH-seeking behavior in rats using a conditioned place preference (CPP) paradigm. The CPP paradigm was first used to determine the effective doses of LY and METH. Four groups were then conditioned with METH (5 mg/kg; i.p.), while the sham group received saline. METH-induced CPP was subsequently extinguished. On the 13th day of extinction, the rats received either METH (0, 1, or 2.5 mg/kg; i.p.) plus vehicle or priming METH plus LY (2 μg/5 μL; i.c.v.). On reinstatement day, preference scores were calculated as the difference in time spent in the drug-paired and vehicle-paired compartments. Rats conditioned with the lowest effective dose of METH (5 mg/kg) exhibited significant differences in pre- and post-testing preference scores. Preference scores were significantly higher in the saline + METH group than in the control group. Furthermore, preference scores were significantly higher in rats that had received priming METH treatment, and pre-treatment with LY significantly attenuated the reinstatement of METH-seeking behavior. These findings suggest that future studies should evaluate the therapeutic potential of 5-HT 1F agonists for preventing relapse in individuals with METH addiction. Highlights • The rate of relapse following cessation of methamphetamine (METH) use is high. • Drug relapse likely involves various subtypes of serotonergic receptors. • Treatment with the 5-HT 1F receptor agonist LY 344864 attenuated METH relapse. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that varenicline, an α4β2 nicotinic receptor partial agonist, and α7 nicotinic receptor full agonist, may be effective for the treatment of methamphetamine (MA) dependence due to dopaminergic effects, relief of glutamatergic and cognitive dysfunction, and activation of nicotinic cholinergic systems. This study aimed to determine if varenicline (1 mg BID) resulted in reduced methamphetamine use compared to placebo among treatment-seeking MA-dependent volunteers.Methods: Treatment-seeking MA-dependent volunteers were randomized to varenicline 1 mg twice daily (n = 27) or placebo (n = 25) and cognitive behavioral therapy for 9 weeks. The primary outcomes were the proportion of participants achieving end-of-treatment-abstinence (EOTA, MA-negative urine specimens during weeks 8 and 9) and the treatment effectiveness score (TES, number of MA-negative urine specimens) for varenicline versus placebo.Results: There was no significant difference in EOTA between varenicline (15%, 4/27) and placebo (20%, 5/25; p = 0.9). There was some suggestion that urinary confirmed medication compliance corresponded with EOTA in the varenicline condition, though it did not reach statistical significance, OR = 1.57 for a 100 ng/ml increase in urine varenicline, p = 0.10, 95% CI (0.99, 3.02). There was no significant difference in mean TES in the varenicline condition (8.6) compared to the placebo condition (8.1), and treatment condition was not a statistically significant predictor of TES, IRR = 1.01, p = 0.9, 95% CI (0.39, 2.70).Conclusions: The results of this study indicate that 1 mg varenicline BID was not an effective treatment for MA dependence among treatment-seeking MA-dependent volunteers. [ABSTRACT FROM AUTHOR]

Stimulant use disorder (SUD) is a significant cause of morbidity and mortality around the world. Stimulants are natural and synthetic compounds that include cocaine, methamphetamines, and prescription stimulants. It is very important for providers before prescribing the stimulants to recognize and understand their high potential for addiction, as well as the consequences of withdrawals and chronic use. Amphetamines and cocaine are both stimulants with similar behavioral properties but with differences in their individual mechanism of action and pharmacokinetic properties. There are multiple clinical effects of stimulants but cardiac complications are the most common cause of death. There are multiple modalities for the treatment of SUD, including psychosocial, pharmacologic, and vaccines. Although these treatments are moderately effective, the treatment plan needs to be carefully customized. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) administration results in addiction and memory impairment. Previous studies have suggested that levo-tetrahydropalmatine ( l -THP), an alkaloid purified from the Chinese herb Corydalis, attenuates the behavioral changes induced by METH. Therefore, in this study, we explored whether l -THP could also protect against the METH-induced memory impairment examined using the Morris water maze (MWM). We found that low dose of METH (1.0 mg/kg) treated for 20 consecutive days prior to the MWM experiment impaired spatial memory retention but not acquisition in mice. In addition, high dose of METH (10.0 mg/kg) treated during the spatial learning phase for five consecutive days impaired both the acquisition and retention of spatial memory. Moreover, both of these impairments induced by METH were reversed by l -THP treatment, indicating a potential protective role of l -THP in METH use. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Methamphetamine dependence is associated with heightened impulsivity and diminished quality of life, but the link between impulsivity and changes in quality of life during treatment has not been examined. We aimed to investigate how different elements of impulsivity predict change in quality of life in the 6 weeks after engaging in treatment. Design: Longitudinal, observational cohort study. Setting: Public and private detoxification and rehabilitation facilities in metropolitan Melbourne, Australia. Participants: One hundred and eight individuals with methamphetamine dependence (81 male) tested within 3 weeks of commencing treatment; 80 (74%) were followed‐up at 6 weeks. Measurements: The Continuous Performance Test‐2 measured impulsive action (cognitive and motor impulsivity); the Delay Discounting Task measured impulsive choice. Quality of life was measured with the World Health Organization Quality of Life Scale—Brief, which includes social, psychological, physical and environment domains. Control variables included age, gender, estimated IQ, depression severity score, methamphetamine dependence severity score, cannabis dependence severity score and treatment modality. Findings: We found that all three forms of impulsivity were significant predictors of change in the social domain: motor impulsivity (β = −0.54, P = 0.013), cognitive impulsivity (β = −0.46, P = 0.029) and impulsive choice (β = −0.26, P = 0.019). Change in the psychological domain was predicted significantly by motor impulsivity (β = −0.45, P = 0.046). Control variables of age and depression were associated significantly with changes in the physical domain. Conclusions: In Australian methamphetamine‐dependent individuals, elevated impulsivity predicts lower improvement of social and psychological quality of life in the first 6–9 weeks of treatment. [ABSTRACT FROM AUTHOR]

There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N -substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or “substitute” treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial. Here, we compared in rats the ability of the BZT analogue and high affinity dopamine (DA) reuptake inhibitor, JHW-007, and the antidepressant, trazodone, administered during extinction sessions after chronic METH self-administration, to alter METH-primed reinstatement of drug seeking. The data showed that trazodone produced paradoxical effects on lever pressing during extinction of METH self-administration, decreasing active, but increasing inactive, lever pressing. JHW-007 did not have any observable effects on extinction training. Importantly, JHW-007 significantly attenuated METH-primed reinstatement, whereas trazodone enhanced it. These findings lend support to the candidacy of selective DA uptake blockers, such as JHW-007, as potential treatments for METH addiction, but not to the use of antidepressant medication as a single therapeutic approach for relapse prevention. [ABSTRACT FROM AUTHOR]

Background: Treatment as Prevention (TasP) leading to increased HIV treatment optimism among men who have sex with men (MSM) has been previously associated with behavioural risk compensation, though not yet via crystal methamphetamine (CM) use. Among HIV-negative MSM in a TasP environment, this study aimed to investigate the prevalence of recent CM use over time, examine the association between HIV treatment optimism and CM use and initiation, and identify correlates of recent CM use and predictors of CM initiation.Methods: Using data from a prospective behavioural cohort study of sexually active MSM in the Vancouver area, we used multi-level generalized mixed effect models to evaluate temporal trends in CM use, univariable and multivariable logistic regression to identify covariates of recent CM use, and univariable and multivariable survival analysis to identify predictors of CM initiation.Results: Of 497 HIV-negative cohort participants, 10.3% reported any recent CM use at enrollment. From 2012-2016, there were no statistically significant temporal trends in overall CM use or with routes of administration. In multivariable logistic regression analyses, HIV treatment optimism was not associated with recent CM use (not retained in final model) or CM initiation (aHR = 1.06, 95% CI:0.98-1.15). Significant correlates of CM use include recent gamma-hydroxybutyrate (GHB) and ecstasy use, and having received/given drugs for sex.Conclusions: Among HIV-negative MSM in Vancouver, HIV treatment optimism does not appear to be independently associated with CM use or initiation of use, though use of CM was both prevalent and stable over time. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. Case Report: A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin. He was admitted to behavioral medicine for further care. Blood cultures were positive for gram-negative rods and he was transferred to the medicine ward. Cultures eventually grew Brevundimonas diminuta. Clindamycin was discontinued and he was started on levofloxacin. Transaminase levels measured soon after levofloxacin administration showed aminotransferase levels raised to approximately 50 times baseline within a few days. Levofloxacin was discontinued due to concern about drug-induced hepatotoxicity. After discontinuation, transaminase levels decreased immediately. Work-up for other causes of transaminitis revealed no other etiology. Conclusions: Clinicians should remain mindful that levofloxacin can induce hepatotoxicity in rare cases. In patients presenting with acute liver injury who have recently taken levofloxacin, it would be wise to remain cognizant of the possibility of levofloxacin-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a widely abused and a severely addictive psychostimulant. Relapse is the main cause of concern when treating addiction. It could manifest after a long period of abstinence. Previous studies showed that there is a strong connection between sleep impairment and relapse. Also, it has been reported that cannabidiol might be a potential treatment for drug craving and relapse. In this study, we used conditioned place preference (CPP) to investigate whether Cannabidiol (CBD), a phytocannabinoid, can prevent METH-induced reinstatement in Rapid Eye Movement Sleep Deprived (RSD) rats. In order to induce CPP, the animals were given METH (1 mg/kg; sc) for five days. The effective priming dose of METH (0.5 mg/kg, sc) reinstated the extinguished METH-induced CPP. In order to investigate the effect of RSD on METH-induced reinstatement, we used the inverted flowerpot technique to deprive the rats of REM sleep. We found that 24 h-RSD could facilitate priming-induced reinstatement of METH. In addition to this, the ICV administration of CBD 10 μg/5 μl could suppress the METH-induced reinstatement even in RSD rats. In conclusion, the administration of CBD 10 μg/5 μl effectively prevents METH-induced CPP, even in a condition of stress. CBD can be considered an agent that reduces the risk of the relapse; however, this requires more investigation. [ABSTRACT FROM AUTHOR]

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

Objectives: The aim of this study was to determine the rates of patient aggression in a psychiatric unit over 12 months and to determine underlying causes, notably the role of substances.Methods: A retrospective file audit was undertaken of all patients admitted to St Vincent's psychiatric unit (Melbourne, Australia) in the first half of 2013 and 2014 involved in an aggressive incident. Patient information included demographics, psychiatric, substance and aggression history. The setting and context of aggression and associated mental state findings were also reviewed.Results: There were 26 aggressive incidents in 2013 and 63 in 2014, perpetrated by 11 and 34 patients respectively. No significant differences were found between the groups' baseline demographics. The 2014 cohort was significantly more likely to have substance use history (odds ratio (OR) 4.83) and have made threats to staff (OR 4.07) but significantly less likely to be distracted by internal stimuli (OR 0.05). There were also (not statistically significant) trends for the 2014 cohort; they were more likely to report a history of alcohol use (OR 3.9); be accompanied to emergency department by police (OR 2.95) and have leave prior to aggression ( χ2 = 7.37).Conclusions: Aggressive incidents more than doubled over 12 months. Substance use appeared to be a major factor associated with aggression. These findings have implications for service provision and training. Further research is needed to better understand and manage substances in psychiatric settings. [ABSTRACT FROM AUTHOR]

Abstract: Methamphetamine (METH) is the primary drug within amphetamine‐type stimulants which are the second most abused group of drugs worldwide. There is no pharmacological treatment addressed specifically to METH addiction, and behavioral therapy is shadowed by poor long‐term recovery and relapse. Therefore, novel approaches to manage METH addiction are an urgent need. This review aims to describe the current state of physical exercise use on methamphetamine addiction management. The following searching terms in PubMed were used: (“physical exercise” OR “exercise”) AND “methamphetamine.” Relevant references from key publications and gray literature were also reviewed to identify additional citations for inclusion. Original investigation regarding physical exercise and methamphetamine addiction (clinical data) or neurobiological mechanisms of physical exercise in animal models of methamphetamine administration (preclinical data) was included. Overall, METH users demonstrated improvements, including better fitness and emotional measures, lower relapse rates, and sustained abstinence when compared to nonexercised individuals. The neurobiological mechanisms of physical exercise in METH users seem to reflect an interplay of several agents, including neurochemicals, oxidative stress, neurogenesis, gliogenesis, and blood‐brain barrier as disclosed by preclinical data. Exercise‐based interventions alone or as a conjoint therapy may be a useful tool for managing METH addiction. [ABSTRACT FROM AUTHOR]

Introduction and Aims: We previously found that residential rehabilitation increased continuous abstinence from methamphetamine use 1 year after treatment. We examine what client and treatment characteristics predict this outcome.Design and Methods: Participants (n = 176) were dependent on methamphetamine and entering residential rehabilitation for methamphetamine use. Simultaneous logistic regression was used to identify independent predictors of continuous abstinence from methamphetamine use at 1 year follow-up. Measures included demographics, drug use, psychiatric comorbidity (Diagnostic and Statistical Manual of Mental Disorders, major depression, social phobia, panic disorder, schizophrenia, mania and conduct disorder), symptoms of psychosis and hostility, readiness to change, motivations for treatment and treatment characteristics (duration, rapport, group and individual counselling).Results: Participants stayed in treatment for a median of 8 weeks; 23% remained abstinent at 1 year. The only independent predictors of abstinence were more weeks in treatment [adjusted odds ratio (AOR) 1.2, P < 0.001], better rapport with treatment providers (AOR 2.4, P = 0.049) and receipt of individual counselling (AOR 3.7, P = 0.013), whereas injecting methamphetamine predicted not achieving abstinence (AOR = 0.25, P = 0.002). Individual counselling and good rapport increased abstinence to 45%; for injectors, longer stays in treatment (13+ weeks) were additionally needed to produce similar abstinence rates (43%).Discussions and Conclusions: Abstinence from methamphetamine use following residential rehabilitation could be significantly increased by providing individual counselling, maintaining good rapport with clients and ensuring longer stays for people who inject the drug. [McKetin R, Kothe A, Baker AL, Lee NK, Ross J, Lubman DI. Predicting abstinence from methamphetamine use after residential rehabilitation: Findings from the Methamphetamine Treatment Evaluation Study. Drug Alcohol Rev 2018;37:70-78]. [ABSTRACT FROM AUTHOR]

Background: Depression symptoms is highly comorbid with methamphetamine (METH) dependence. Except for the role in the pathophysiology of depression symptoms, brain-derived neurotrophic factor (BDNF) is also involved in the METH dependence. The present study aims to explore whether BDNF plays a role in the development of depression symptoms during METH withdrawal.Methods: We recruited 179 patients with METH dependence who were followed up for two weeks. Ultimately, 131 (73.2%) patients finished the follow-up. Besides, 90 healthy controls were also recruited. Serum BDNF levels were measured by DuoSet ELISA Development System upon admission. The short form (13 items) of the Beck Depression Inventory (BDI) and Amphetamine Withdrawal Questionnaire (AWQ) were used to measure the depression and withdrawal symptoms. Patients with BDI score ≥ 8 were identified to have depression symptoms.Results: Of the 131 patients, 64 (48.9%) were identified to have depression symptoms at the two-week endpoint. Patients with depression symptoms showed significantly lower BDNF levels than those with no depression symptoms. Serum BDNF levels (≤ 1251.0pg/ml) were independently associated with the development of depression symptoms during METH withdrawal (OR = 3.50, 95% CI, 1.14-10.73, p = 0.028).Limitations: BDNF levels were tested in serum but not in brain and the baseline BDI and AWQ scores between the depression and non-depression groups were not matched. Besides, the follow-up time was relatively short.Conclusions: Our study demonstrated that patients with serum BDNF levels ≤ 1251.0pg/ml had higher risk of depression symptoms during METH withdrawal. [ABSTRACT FROM AUTHOR]

Postmortem investigation of methamphetamine (MA) abuse is an important task in forensic pathology. The present study investigated morphological changes in the astrocytes in the parietal cerebral cortex of MA abusers. Glial fibrillary acidic protein immunoreactivity in the cerebral cortex was examined in forensic autopsy cases for MA-detected group and control group. Clasmatodendrotic astrocytes (including those with swollen cell bodies and disintegrating distal processes) were frequently observed in the cerebral cortex of MA abusers. Quantitative analysis using a colour image processor showed a concomitant increase in the astrocyte area and astrocyte-to-vessel area ratio (size and number of astrocytes) in the grey matter in acute MA fatality and other MA-involved cases, although the astrocyte area (size) was also increased in cases of asphyxiation. The total astrocyte area (size) in the white matter was significantly higher in MA fatalities and asphyxia than in the other groups involving MA abusers. Those indices were independent of blood MA level, age, sex, survival or postmortem time. These observations suggest the increasing number and hypertrophic changes of astrocytes in the grey matter in MA abusers can be the outcome of long-term abuse, while disintegrating distal processes may exist only in acute fatal MA intoxication. [ABSTRACT FROM PUBLISHER]

Aim To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute agitation. Design and setting A multi-centre, randomized, double-blind, controlled, clinical trial was conducted in two Australian emergency departments, between October 2014 and September 2015. Participants Three hundred and sixty-one patients, aged 18-65 years, requiring intravenous medication sedation for acute agitation, were enrolled into this study. We report the results of a subgroup of 92 methamphetamine-affected patients. Intervention and comparator Patients were assigned randomly to receive either an intravenous bolus of midazolam 5 mg-droperidol 5 mg combined, droperidol 10 mg or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg or olanzapine 5 mg, respectively. Measurements The primary outcome was the proportion of patients sedated adequately at 10 minutes. Odds ratios with 95% confidence intervals (ORs, 95% CI) were estimated. Findings The baseline characteristics of patients in the three groups were similar. At 10 minutes, significantly more patients in the midazolam-droperidol group [29 of 34 (85.3%)] were sedated adequately compared with the droperidol group [14 of 30 (46.7%), OR = 6.63, 95% CI = 2.02-21.78] or with the olanzapine group [14 of 28 (50.0%), OR 5.80, 95% CI = 1.74-19.33]. The number of patients who experienced an adverse event (AE) in the midazolam-droperidol, droperidol and olanzapine groups was seven of 34, two of 30 and six of 28, respectively. The most common AE was oxygen desaturation. Conclusion A midazolam-droperidol combination appears to provide more rapid sedation of patients with methamphetamine-related acute agitation than droperidol or olanzapine alone. [ABSTRACT FROM AUTHOR]

Background and Aims High rates of loss to follow-up represent a significant challenge to clinical trials of pharmacological treatments for methamphetamine (MA) use disorder. We aimed to estimate and test the relationship between achieving and maintaining abstinence in the initial weeks of study participation and subsequent retention in such trials, hypothesizing that participants able to achieve early abstinence would be less likely to drop out. Design Data from four randomized controlled trials (RCTs) of pharmacological treatments for MA use disorder were pooled and analyzed using a random-effects approach. Setting All trials were conducted in the greater Los Angeles, CA, USA area. Participants A total of 440 participants were included; trials were conducted between 2004 and 2014. Measurements Participants' ability to achieve a brief period of initial abstinence was measured as the number of MA-negative urine screens completed in the first 2 weeks of the trials. Outcomes were the likelihood of dropout, i.e. missing two consecutive weeks of scheduled urine drug screens, and the number of days participants were retained in the trials. Findings Study participants achieved an average of three (of six possible) negative urine screens during the first 2 weeks of the trials, 51% dropped out and the average number of days retained was 60 (of 90 maximum). Each additional negative urine screen achieved during the first 2 weeks of the study reduced multiplicatively the odds of dropout by 41% [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.53, 0.66]. Abstinence was also a significant predictor of retention time; the hazard ratio for non-completion was 0.75 per additional negative urine screen (95% CI = 0.71, 0.80). Conclusions Participants in randomized controlled trials of pharmacological treatments for methamphetamine use disorder who are able to achieve a brief period of early abstinence are retained longer in the trials and are less likely to drop out overall. [ABSTRACT FROM AUTHOR]

Background Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. Methods We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed. Results Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens. Conclusions Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans. [ABSTRACT FROM AUTHOR]

Background: Despite rapid increases in crystal methamphetamine (CM) use worldwide and established gendered patterns of use, empirical research on CM injection initiation among sex workers is limited. Given the wide range of harms associated with CM, alongside stimulant effects including sexual dis-inhibition and prolonged awake-ness, this study aimed to longitudinally investigate socio-structural predictors of initiating CM injection among sex workers in Vancouver, Canada.Methods: Data (2010-2014) were drawn from a community-based cohort of women sex workers: AESHA (An Evaluation of Sex Workers Health Access). Participants completed bi-annual interviewer-administered questionnaires and HIV/STI testing. Kaplan Meier methods and Cox proportional hazards regression were used to model predictors of CM injection initiation among CM injection-naïve participants.Results: Of 455 participants eligible at baseline, 14.3% (n=65) injected CM for the first time over follow-up, with an incidence density of 6.79 per 100 person-years (95% Confidence Interval [CI] 5.30-8.69). In multivariable analysis, injection heroin use (Adjusted Hazard Ratio [AHR] 6.11; 95%CI 3.24-11.52), having an intimate partner who injects drugs (AHR 2.93; 95%CI 1.57-5.46), workplace violence (AHR 2.85; 95%CI 1.74-4.67), HIV seropositivity (AHR 2.69; 95%CI 1.45-5.00), and childhood abuse (AHR 1.86; 95%CI 0.99-3.49) were independently associated with initiating CM injection.Conclusions: Findings underscore the gendered and social risk environment of CM injection initiation among sex workers. The strong influences of historical/workplace violence, coupled with heroin injection (known to be self-medicating for post-traumatic stress) as a primary risk pathway, emphasize the urgency of increasing access to integrated, trauma-informed addiction treatment and HIV care for marginalized women. [ABSTRACT FROM AUTHOR]

Methamphetamine dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of methamphetamine dependence. N-acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N-acetylcysteine also has antioxidant properties that protect against methamphetamine-induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of methamphetamine. This commentary overviews the actions of N-acetylcysteine and evidence for its efficacy in treating addiction with a particular focus on its potential utility for methamphetamine dependence. We conclude that the preliminary evidence indicates a need for full-scale trials to definitively establish whether N-acetylcysteine has a therapeutic benefit and the nature of this benefit, for managing methamphetamine dependence. [McKetin R, Dean O, Baker A. L, Carter G, Turner A, Kelly P. J, Berk M. A potential role for N-acetylcysteine in the management of methamphetamine dependence. Drug Alcohol Rev 2017;36:153-159]. [ABSTRACT FROM AUTHOR]

Introduction: Methamphetamine (MA) abuse remains a global health challenge despite intense research interest in the development of pharmacological treatments. This review provides a summary of clinical trials and human studies on the pharmacotherapy of methamphetamine use disorder (MUD). Areas covered: We summarize published clinical trials that tested candidate medications for MUD and also conducted PubMed and Google Scholar searches to identify recently completed clinical trials using the keywords ‘methamphetamine’ ‘addiction’ ‘pharmacotherapy’ and ‘clinical trial.’ To determine the status of ongoing clinical trials targeting MUD, we also searched the ClinicalTrials.gov online database. We conclude this review with a discussion of current research gaps and future directions. Expert commentary: Clinical trials examining the potential for pharmacotherapies of MUD have largely been negative. Future studies need to address several limitations to reduce the possibility of Type II errors: small sample sizes, high dropout rates or multiple comorbidities. Additionally, new treatment targets, such as MA-induced disruptions in cognition and in the neuroimmune system, merit trials with agents that selectively modulate these processes. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) abuse is a major public health and safety concern throughout the world and a growing burden on healthcare costs. The purpose of the present study was to investigate the protective effect of fluoxetine against MA-induced chronic pulmonary inflammation and to evaluate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidative stress. Wistar rats were divided into control, MA and two fluoxetine-treated groups. Rats in the MA and the two fluoxetine-treated groups were treated daily with intraperitoneal injection of 10 mg/kg MA twice daily. Rats in the two fluoxetine-treated groups were injected intragastrically with fluoxetine (2 and 10 mg/kg) once daily, respectively. After 5 weeks, the rats were euthanized and hematoxylin and eosin staining, immunohistochemistry, western blot analysis and redox assay were performed. It was demonstrated that chronic exposure to MA can induce pulmonary inflammation in rats, with the symptoms of inflammatory cell infiltration, crowded lung parenchyma, thickened septum and a reduced number of alveolar sacs. Fluoxetine attenuated pulmonary inflammation and the expression of interleukin-6 and tumor necrosis factor-α in rat lungs. Fluoxetine inhibited MA-induced increases in the expression levels of serotonin transporter (SERT) and p-p38 mitogen-activated protein kinase (MAPK), and reversed the MA-induced decrease in nuclear Nrf2 and human heme oxygenase-1 in lungs. Fluoxetine at 10 mg/kg significantly reversed the reduced glutathione (GSH) level, the ratio of GSH/oxidized glutathione, and the reactive oxygen species level in rat lungs from the MA group. These findings suggested that fluoxetine, a SERT inhibitor, has a protective effect against MA-induced lung inflammation by suppressing oxidative stress through the SERT/p38 MAPK/Nrf2 pathway in rats. [ABSTRACT FROM AUTHOR]

Rates of anxiety disorders among individuals who use methamphetamine are estimated to be as high as 30.2%. The presence of an anxiety disorder in methamphetamine users is associated with higher rates of relapse, non-adherence to treatment and poorer outcomes relative to methamphetamine users without an anxiety disorder. A review investigating current treatment options for methamphetamine dependence or withdrawal from methamphetamine was conducted using PubMed, CINAHL and PsycINFO. The focus of the review was trials that utilized an intervention and collected anxiety as an outcome measure. Seven studies were included in the review, and five of these studies examined a pharmacotherapy option, one studied a psychosocial intervention and one study investigated exercise as an intervention. Some of the pharmacotherapy studies and the study of exercise were associated with improvements in mood and/or a reduction in methamphetamine use. Concerns of sample size and measurement of anxiety were raised. Future well-designed research with large sample sizes is warranted to examine how to manage anxiety among methamphetamine users. [ABSTRACT FROM AUTHOR]

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

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

Background: Methamphetamine use is associated with a range of poor health, social and justice outcomes. In many parts of the world increased methamphetamine use has been identified as a major public health concern. Methamphetamine treatment programmes have been effective in reducing and ceasing use, however a range of barriers have prevented these programmes being widely adopted by methamphetamine users. This review examines the barriers to accessing meth/amphetamine treatment identified in the literature.Methods: Databases were systematically searched using relevant terms for peer-reviewed articles describing original research exploring the barriers to accessing treatment for meth/amphetamine use. Reviews and grey literature were excluded. Eleven studies conducted in 5 countries were included in data synthesis; this involved a systematic review of all 11 studies, and meta-analysis of the prevalence of barriers reported in 6 studies that published sufficient quantitative data.Results: Psychosocial/internal barriers to accessing methamphetamine treatment were most prevalent across studies (10/11 studies). Meta-analysis confirmed the four most commonly endorsed barriers to treatment access across studies all psychosocial barriers were embarrassment or stigma (60%, 95% CI: 54-67%); belief that treatment was unnecessary (59%, 95% CI:54-65%); preferring to withdraw alone without assistance (55%, 95% CI:45-65); and privacy concerns (51%, 95% CI:44-59%).Conclusions: The primary barriers to accessing methamphetamine treatment are psychosocial/internal. Services and treatment models that address these barriers are urgently required. There is a growing need for methamphetamine-appropriate treatment services. Further research evaluating treatment engagement and effectiveness for methamphetamine and polysubstance use, including the development of effective pharmacotherapies is warranted. [ABSTRACT FROM AUTHOR]

Binge/crash cycles of methamphetamine (MA) use are frequently reported by individuals suffering from MA use disorders. A MA binge is self-reported as multiple daily doses that commonly accumulate to 800 mg/day (~10 mg/kg/day for a 170 pound human). A genetic animal model with a similar vulnerability to binge-level MA intake is missing. We used selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mouse lines to determine whether several procedural variations would result in binge-level MA intake. Data were also collected in two progenitor populations of the MA drinking lines, the DBA/2J (D2) strain and the F2 cross of the D2 and C57BL/6J strains. The impact of 3 factors was examined: (1) concentration of MA in the two-bottle choice procedure used for selective breeding; (2) ratio of bottles containing MA vs. water, and (3) length of the withdrawal (or abstinence) period between MA drinking sessions. When MA concentration was progressively increased every 4 days in 20 mg/l amounts from 20 to 140 mg/l, maximum intake in MALDR mice was 1.1 mg/kg, whereas MAHDR mice consumed as much as 14.6 mg/kg. When these concentrations were tested in a multiple bottle choice procedure, the highest ratio of MA to water bottles (3:1) was associated with escalated MA intake of up to 29.1 mg/kg in MAHDR mice and 12.0 mg/kg in F2 mice; MALDR mice did not show a ratio-dependent escalation in MA intake. Finally, MAHDR and D2 mice were offered 3 bottles of MA vs. water at increasing concentrations from 20 to 80 mg/l, and tested under an intermittent 6-h withdrawal period, which was lengthened to 30 h (D2 mice) or to 30 or 78 h (MAHDR). D2 and MAHDR mice initially consumed similar amounts of 14–16 mg/kg MA, but D2 mice reduced their MA intake 3-fold after introduction of 30-h abstinence periods, whereas MAHDR mice retained their high level of intake regardless of withdrawal period. MAHDR mice provide a genetic model of binge-level MA intake appropriate for the study of associated MA-induced neurobiological changes and pharmaceutical treatments. [ABSTRACT FROM AUTHOR]

There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, IC KLH -SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the IC KLH -SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) addiction is a serious public health problem, and current methods to abate addiction and relapse are currently ineffective for mitigating this growing global epidemic. Development of a vaccine targeting MA would provide a complementary strategy to existing behavioral therapies, but this has proven challenging. Herein, we describe optimization of both hapten design and formulation, identifying a vaccine that elicited a robust anti-MA immune response in mice, decreasing methamphetamine-induced locomotor activity. [ABSTRACT FROM AUTHOR]

Background: Despite the effectiveness of psychosocial programs for recovery from drug use problems, there have been challenges in implementation of treatment. Internet-based and computerized approaches have been known to be effective in treatment dissemination. The study purpose is to assess the effects of a web-based psychosocial relapse prevention program with a multicenter randomized controlled trial. Methods: Recruitment began in January 2015 for outpatient participants diagnosed with drug abuse or dependence who have used a primary abused drug in the past year at psychiatric hospitals and a clinic. Participants are randomized either to a web-based relapse prevention program or a self-monitoring group. The intervention is a web-based relapse prevention program named "e-SMARPP" that consists of six relapse prevention program modules with tailored feedback from health care professionals and 8 weeks of self-monitoring. The content is adapted from a face-to-face relapse prevention program which is based on cognitive behavioral therapy and motivational enhancement. The primary outcomes are relapse risk assessed by the Stimulant Relapse Risk Scale (baseline, 2-, 5- and 8-month) and the longest duration of consecutive abstinent days from primary abused drug during the intervention. Secondary outcomes will include motivation to change, self-efficacy for drug use and craving, abstinent days in the past 28 or 56 days, quality of life, sense of coherence, cost of substance use, medical cost, retention of treatment and use of self-help group. Completion, usability and satisfaction of the program will be also assessed to explore feasibility. This study protocol was approved by the Ethics Committee of The University of Tokyo and each recruiting hospital and clinic. Discussion: To our knowledge, this study is the first clinical trial to assess the effects of a web-based therapeutic program for drug users in Japan. If successful, this program is a promising approach for drug user treatment in Japan, where the stigma toward drug users is strong. The results are also useful for researchers who want to know about programs for various substances, including methamphetamine. [ABSTRACT FROM AUTHOR]

The neuropeptide oxytocin (OT), given acutely, reduces self-administration of the psychostimulant drug methamphetamine (METH). Additionally, chronic OT administration to adolescent rats reduces levels of alcohol consumption in adulthood, suggesting developmental neuroplasticity in the OT system relevant to addiction-related behaviors. Here, we examined whether OT exposure during adolescence might subsequently inhibit METH self-administration in adulthood. Female Sprague-Dawley rats were administered vehicle or OT (1 mg/kg, i.p.) once daily from postnatal days (PND) 28 to 37 (adolescence). At PND 62 (adulthood), rats were trained to self-administer METH (intravenous, i.v.) in daily 2-hour sessions for 10 days under a fixed ratio 1 (FR1) reinforcement schedule, followed by determination of dose-response functions (0.01-0.3 mg/kg/infusion, i.v.) under both FR1 and progressive ratio (PR) schedules of reinforcement. Responding was then extinguished, and relapse to METH-seeking behavior assessed following priming doses of non-contingent METH (0.1-1 mg/kg, i.p.). Finally, plasma was collected to determine pre-treatment effects on OT and corticosterone levels. Results showed that OT pre-treatment did not significantly inhibit the acquisition of METH self-administration or FR1 responding. However, rats pre-treated with OT responded significantly less for METH under a PR reinforcement schedule, and showed reduced METH-primed reinstatement with the 1 mg/kg prime. Plasma OT levels were also significantly higher in OT pre-treated rats. These results confirm earlier observations that adolescent OT exposure can subtly, yet significantly, inhibit addiction-relevant behaviors in adulthood. [ABSTRACT FROM AUTHOR]

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

Background: Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Methods: Adolescent or adult male Sprague-Dawley rats received either nicotine water (10.75 μg/mL) or tap water for several weeks. Methamphetamine (4 × 7.5 mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Results: Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Conclusions: Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which novel object recognition deficits are attenuated by nicotine in methamphetamine-treated rats. [ABSTRACT FROM AUTHOR]

Trismus is one of the side effects of methamphetamine use which is associated with contractions of the jaw muscles. Acupuncture is a traditional and complementary treatment that is effective in reducing pain and psychological indices. The purpose of this study was to investigate the effectiveness of the acupuncture in a case of trismus caused by methamphetamine abuse. The patient was a 31-year-old man with a history of chronic methamphetamine use, reported to have dependence and severe jaw pain. In a single case study and in an ABAB design with multi-baselines, we used acupuncture for 3 weeks to reduce pain and addiction severity index (ASI). Data were analyzed through a generalized estimating equation (GEE). The results showed that there was no significant correlation between severity of addiction and pain (P > 0.05). Due to damage caused in the process of production of tyrosine hydroxylase and mitogen-activated protein kinase and the role of these precursors in the production of dopamine as an effective factor in the acupuncture, the effectiveness of this treatment can be limited. [ABSTRACT FROM AUTHOR]

Background This paper examines a methamphetamine treatment and peer support program for gay men and other men who have sex with men (MSM) who use methamphetamine. Australian MSM use illicit drugs including methamphetamine at significantly higher rates than the broader community.1,2 Methamphetamine rates are higher again amongst HIV positive MSM. Methamphetamine in the MSM community is associated with sexual activity and may be associated with psychosocial harms including risk of the transmission of HIV and sexually transmissible infections.3,4,7,8 Methods: This paper presents the formal evaluation of Re-Wired, Australia's first structured methamphetamine treatment and support program for MSM, consisting of a free, six week therapeutic group and Re-Wired 2.0, a follow up peer support group. Data collection included baseline and post intervention administration of the Kessler Scale of Psychological Distress (K10) and the Drug Use Disorders Identification Test (DUDIT), the Personal Wellbeing Index (PWI) and the Readiness to Change Questionnaire (RCQ). This was complemented with qualitative session feedback and a small number of post intervention participant interviews.Results: Program evaluation demonstrated modest improvements in participant psychological distress, personal well-being and stage of change and reductions in methamphetamine use post intervention. Qualitative data revealed benefits of a specialised harm reduction intervention for this population through addressing fear of discrimination and stigma.Conclusions: The presented harm reduction program for MSM who use methamphetamine demonstrates the potential for a specialist peer-based approach to reduce harm in this vulnerable population. This approach may be suitable for adaptation with MSM populations in similar high-income settings. [ABSTRACT FROM AUTHOR]

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

In this research, the possible neuropsychological predictors of relapse and dropout of group cognitive behavioral therapy (CBT) for methamphetamine (MA) users were explored. Participants were 42 MA users sentenced by the judicial system to take part in an out-patient relapse prevention program for MA abuse and dependence that employs a CBT model once a week over the course of 12 weeks. Baseline neuropsychological functions were evaluated with the Conners’ Continuous Performance Test, Wisconsin Card Sorting Test, Iowa Gambling Task, and Barratt Impulsiveness Scale. All participants had to submit to urine drug tests every week. Of the 42 participants, 69.0% had a MA positive urine screening result at least once throughout the program (relapse), while 40.5% dropped out of the treatment program prior to its completion. Short duration of MA abstinence at baseline and poor attention predicted relapse. Predictors of dropout included being unmarried and having risky decision making. Findings may be helpful for clinicians, who can screen for the aforementioned risk factors and provide strategies for high-risk patients to help prevent relapse and dropout among MA users in treatment programs. [ABSTRACT FROM PUBLISHER]

Background and Objectives This paper expands on a study investigating depression outcomes in response to an 8-week exercise intervention among methamphetamine (MA) dependent individuals in early recovery. Methods A total of 135 MA-dependent individuals enrolled in residential treatment were randomly assigned to either a structured exercise intervention or a structured health education control group. Both groups were similar in format: 60-minute sessions, offered three times a week over an 8-week study period. Results Results showed that at the 8-week trial endpoint, participants randomized to the exercise intervention showed significantly greater reduction in depression symptom scores than participants randomized to the health education group, and that participants who attended the greatest number of exercise sessions derived the greatest benefit. This paper further analyzes study data to uncover individual predictors of depression response to exercise and finds that among participants randomized to exercise treatment, individuals with the most severe medical, psychiatric, and addiction disease burden at baseline showed the most significant improvement in depressive symptoms by study endpoint. Conclusions Our findings suggest that exercise in moderate dose is effective at treating depressive symptoms in individuals in early recovery from addiction, and furthermore, that treatment with exercise appears to be particularly beneficial to individuals who suffer from severe medical, psychiatric, and addictive disorders. (Am J Addict 2015;24:246-251) [ABSTRACT FROM AUTHOR]

Background: Persistent methamphetamine (METH) psychosis is a psychotic state beyond 1-month after abstinence, for which there is no effective treatment. This study aimed to evaluate the effectiveness of electroconvulsive therapy (ECT) in persistent METH psychosis patients hospitalized at Shahid Beheshti Hospital, Kerman, Iran, from 6 September 2012 until 6 September 2013, who were not remitted after treatment with olanzapine. Methods: This research was a pilot study on hospitalized patients. After 4 weeks of treatment with olanzapine, 10 out of 71 studied patients did not show complete remission of psychotic symptoms despite their response to the treatment. The mentioned 10 patients were divided into 2 groups by random digit numbers. 5 patients had continued olanzapine and other 5 received 6 sessions of bilateral ECT every other day in addition to olanzapine. Findings: Remission rate of patients in the initial 4 weeks was 78.7%. Reduction in total brief psychiatric rating scale (BPRS) scale at the end of 1-week compared with the next week demonstrated improvement in the symptoms until the end of the study. There was no significant difference in BPRS scores between weeks 4 and 6 in the two groups. Conclusion: This research demonstrated that few sessions of ECT in persistent METH psychosis will not lead to remission in all patients. [ABSTRACT FROM AUTHOR]

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

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 stringent 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. [ABSTRACT FROM AUTHOR]

Background Oxidative stress can result in damage to the brain and other organs. To protect from oxidative damage, the human body possesses molecular defense systems, based on the activity of antioxidants, and enzymatic defense systems, including the enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Although pre-clinical research has shown that stimulant use is associated with oxidative damage, oxidative stress and the antioxidant defense systems have not been evaluated in clinical samples of stimulant-dependent patients. Objectives This study aimed to investigate the link between stimulant dependence and oxidative stress. Methods Peripheral blood samples from 174 methamphetamine ( n = 48) and/or cocaine-dependent ( n = 126) participants as well as 30 normal control participants were analyzed for the enzyme activities of CAT, SOD, and GSH-Px in the erythrocytes and the total antioxidant capacity and the malondialdehyde concentration in the plasma. Results We could show an association of stimulant dependence with a depletion of total antioxidant capacity to 54.6 ± 4.7%, which correlates with a reduced activity of the SOD to 71.3 ± 0.03% compared with healthy control participants (100%). Conclusion Stimulant-dependent patients had significantly lower antioxidant capacity relative to controls, suggesting that they may be at greater risk for oxidative damage to the brain and other organs. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study assessed clinical scenarios of continuing monoclonal antibody (mAb) treatment for (+)-methamphetamine (METH) addiction, and the implications of missing or discontinuing this therapy. We hypothesized that chronic anti-METH mAb7F9 (METH K D = 9 nM) treatment of rats could significantly decrease METH-induced behaviors; even with repeated METH challenges, use of METH doses in excess of mAb binding sites, and after discontinuing mAb treatment which results in a 10-fold reduction in mAb7F9 serum concentrations. Male Sprague Dawley rats ( n = 6/group) were treated with i.v. saline or a loading dose of mAb7F9 to achieve instant steady-state conditions followed by two weekly (141 mg/kg) doses ending on day 14. METH (0.56 mg/kg) was administered 4 h and three days after each saline or mAb7F9 treatment, and on day 21. This produced locomotion and rearing behavior that lasted about 120 min in control rats. In mAb7F9 treated rats, METH-induced distance traveled was significantly reduced from 60 to 120 min ( P < 0.05) on days 0–21 and rearing was significantly reduced from 60 to 120 min on days 0–17. METH serum concentrations determined 5 h after METH dosing was significantly increased in mAb7F9-treated rats after all METH challenges. On days 24 and 28 (the final day), the rats were administered a 3-fold higher METH dose (1.68 mg/kg). MAb7F9 treated rats showed a substantially earlier termination of the METH-induced locomotion on both days, even though the METH dose exceeded mAb7F9s binding capacity. METH brain concentrations determined 5 h after METH on day 28 were also significantly decreased in mAb7F9-treated rats. In conclusion, over one month, mAb7F9 significantly and continuously bound METH and reduced METH-induced locomotor effects even after discontinuation of mAb treatment and challenge with higher METH doses. [ABSTRACT FROM AUTHOR]

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

The article discusses a study which examined outcomes for methamphetamine users following treatment across a range of domains. Topics include poor engagement of methamphetamine users with specialist treatment, reasons for poor rates of treatment engagement, and the positive changes observed among patients one year after treatment engagement.