Gegen-Qinlian decoction-A traditional Chinese medicine formula-Alleviates methamphetamine withdrawal induced anxiety by targeting GABAergic interneuron-pyramidal neuron pathway in mPFC.

Methamphetamine (Meth) withdrawal elicits anxiety, which is a public health concern with limited therapeutic options. Previous studies implied a strong correlation between mPFC and Meth withdrawal. Here, we examined the role of Gegen-Qinlian decoction (GQD) in Meth withdrawal anxiety and explored potential therapeutic targets in mPFC. We found that intra-gastric administration of GQD during the withdrawal period efficiently alleviated anxiety-like behaviours in Meth-withdrawn mice. Further, GQD could restore Meth withdrawal-triggered pathway of GABAergic interneurons (GABA IN)-pyramidal neurons (PN) in the mPFC of Meth-withdrawn mice, especially the prelimbic cortex (PrL) sub-region and PV-positive GABA IN. While, GQD had no obvious effects on the glial cells in the mPFC of Meth-withdrawn mice. By transcriptomic analysis and validation of several gene candidates, we found that genes in the MAPK signalling pathway, especially those related to heat shock proteins, including Hspa1a, Hspa1b and Hspb1, might be GQD-targeting genes in mPFC to treat Meth withdrawal anxiety, as indicated that these genes were up-regulated by Meth withdrawal but rescued by GQD in mPFC. Collectively, our findings identified for the first time that GQD could efficiently alleviate Meth withdrawal anxiety, partially through regulating the local GABA IN-PN pathway and transcriptomic profile of mPFC. The present study confirms that TCM, such as GQD, will be a desirable therapeutic approach in the treatment of drug addiction and related emotional deficits.

Rhynchophylline inhibits methamphetamine dependence via modulating the miR-181a-5p/GABRA1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a plant species that is routinely devoted in traditional Chinese medicine to treat central nervous system disorders. Rhynchophylline (Rhy), a predominant alkaloid isolated from Uncaria rhynchophylla (Miq.) Miq. ex Havil., has been demonstrated to reverse methamphetamine-induced (METH-induced) conditioned place preference (CPP) effects in mice, rats and zebrafish. The precise mechanism is still poorly understood, thus further research is necessary. AIM OF STUDY: This study aimed to investigate the role of miRNAs in the inhibitory effect of Rhy on METH dependence. MATERIALS AND METHODS: A rat CPP paradigm and a PC12 cell addiction model were established. Microarray assays were used to screen and identify the candidate miRNA. Behavioral assessment, real-time PCR, dual-luciferase reporter assay, western blotting, stereotaxic injection of antagomir/agomir and cell transfection experiments were performed to elucidate the effect of the candidate miRNA and intervention mechanism of Rhy on METH dependence. RESULTS: Rhy successfully reversed METH-induced CPP effect and the upregulated miR-181a-5p expression in METH-dependent rat hippocampus and PC12 cells. Moreover, suppression of miR-181a-5p by antagomir 181a reversed METH-induced CPP effect. Meanwhile, overexpression of miR-181a-5p by agomir 181a in combination with low-dose METH (0.5 mg/kg) elicited a significant CPP effect, which was blocked by Rhy through inhibiting miR-181a-5p. Finally, the result demonstrated that miR-181a-5p exerted its regulatory role by targeting γ-aminobutyric acid A receptor α1 (GABRA1) both in vivo and in vitro. CONCLUSION: This finding reveals that Rhy inhibits METH dependence via modulating the miR-181a-5p/GABRA1 axis, which may be a promising target for treatment of METH dependence.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction.

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Virtual Digital Psychotherapist App-Based Treatment in Patients With Methamphetamine Use Disorder (Echo-APP): Single-Arm Pilot Feasibility and Efficacy Study.

BACKGROUND: Substance use disorder is one of the severe public health problems worldwide. Inequitable resources, discrimination, and physical distances limit patients' access to medical help. Automated conversational agents have the potential to provide in-home and remote therapy. However, automatic dialogue agents mostly use text and other methods to interact, which affects the interaction experience, treatment immersion, and clinical efficacy. OBJECTIVE: The aim of this paper is to describe the design and development of Echo-APP, a tablet-based app with the function of a virtual digital psychotherapist, and to conduct a pilot study to explore the feasibility and preliminary efficacy results of Echo-APP for patients with methamphetamine use disorder. METHODS: Echo-APP is an assessment and rehabilitation program developed for substance use disorder (SUD) by a team of clinicians, psychotherapists, and computer experts. The program is available for Android tablets. In terms of assessment, the focus is on the core characteristics of SUD, such as mood, impulsivity, treatment motivation, and craving level. In terms of treatment, Echo-APP provides 10 treatment units, involving awareness of addiction, motivation enhancement, emotion regulation, meditation, etc. A total of 47 patients with methamphetamine dependence were eventually enrolled in the pilot study to receive a single session of the Echo-APP-based motivational enhancement treatment. The outcomes were assessed before and after the patients' treatment, including treatment motivation, craving levels, self-perception on the importance of drug abstinence, and their confidence in stopping the drug use. RESULTS: In the pilot study, scores on the Stages of Change Readiness and Treatment Eagerness Scale and the questionnaire on motivation for abstaining from drugs significantly increased after the Echo-APP-based treatment (P<.001, Cohen d=-0.60), while craving was reduced (P=.01, Cohen d=0.38). Patients' baseline Generalized Anxiety Disorder-7 assessment score (ß=3.57; P<.001; 95% CI 0.80, 2.89) and Barratt Impulsiveness Scale (BIS)-motor impulsiveness score (ß=-2.10; P=.04; 95% CI -0.94, -0.02) were predictive of changes in the patients' treatment motivation during treatment. Moreover, patients' baseline Generalized Anxiety Disorder-7 assessment score (ß=-1.607; P=.03; 95% CI -3.08, -0.14), BIS-attentional impulsivity score (ß=-2.43; P=.004; 95% CI -4.03, -0.83), and BIS-nonplanning impulsivity score (ß=2.54; P=.002; 95% CI 0.98, 4.10) were predictive of changes in craving scores during treatment. CONCLUSIONS: Echo-APP is a practical, accepted, and promising virtual digital psychotherapist program for patients with methamphetamine dependence. The preliminary findings lay a good foundation for further optimization of the program and the promotion of large-scale randomized controlled clinical studies for SUD.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Effectiveness of Mindfulness - Based Therapy and Counseling programs (MBTC) on relapses to methamphetamine dependence at a substance dependency treatment center.

This non-concurrent controlled intervention study aimed to examine the effectiveness of the Mindfulness - Based Therapy and Counseling programs (MBTC) on the treatment of methamphetamine use disorder among 70 individuals (37 females) receiving methamphetamine dependency treatment. Participants were divided into a control group undergoing the usual program and an experimental group using MBTC plus the usual program at a treatment center in Thailand. The study was conducted using the Methamphetamine Craving Questionnaire, urine Color Immunochromatographic Assay and the Mini-International Neuropsychiatric Interview. Stress, depression, and mindfulness were also assessed. MBTC comprised of practicing mindfulness for 90-120 min weekly for eight weeks. Participants were assessed before and after the treatment(s) and at follow-ups visits at 2, 4, 8, 12, and 24 weeks. Mean age (30.3 ± 5.8 years), age of first methamphetamine use (18.2 ± 4.5 years) and other demographics did not differ between groups. At six-month follow-up, the experimental group had significantly lower craving (-7.89, 95%CI = -15.47, -0.32), stress (-7.44, 95%CI = -12.21, -2.67), and depression (-2.95, 95%CI = -5.31, -0.6) and statistically significant higher mindfulness scores (12.86, 95%CI = 9.37, 16.35) than the control group. In addition, methamphetamine relapse in the MBTC group (5/35, 14.3%) was significantly lower than the control group (16/35, 45.7%).

Electroacupuncture alleviates spatial memory deficits in METH withdrawal mice by enhancing astrocyte-mediated glutamate clearance in the dCA1.

Methamphetamine (METH) elicits endogenous glutamate (Glu) in the brain, which could partially explain METH-induced memory deficits. Here, we investigated the therapeutic effects of electroacupuncture (EA) on spatial memory deficits in METH withdrawal mice and its potential synaptic mechanisms. We found that EA at acupoints 'Baihui' and 'Yintang' ameliorated the impaired spatial memory in METH withdrawal mice. In parallel, EA attenuated the Glu levels in vivo and suppressed the neuronal activities within dCA1 of METH withdrawal mice, as indicated by the decreasing c-Fos levels and the amplitude of mEPSP. In the dCA1, EA decreased A1-like astrocytes but increased astrocytic glutamatergic transporting molecules including glutamate transporter 1 and glutamine synthase. However, EA seemed to have no effects on presynaptic Glu transmission from the dCA3, as evidenced by the similiar levels of c-Fos in the dCA3 neurons, synaptic vesicular markers of dCA3 neural terminals and values of paired-pulse ratio in the dCA1 neurons between EA-treated and sham EA-treated METH withdrawal mice. These findings suggest that EA might normalize the dCA1 Glu levels at least in part through enhancing astrocyte-mediated Glu clearance. Taken together, astrocytes might be a novel target for developing therapeutic interventions against the impaired memory behaviours in METH users, and EA represents a promising non-invasive therapeutic strategy for the management of drug-caused memory deficits.

Four-week Tai Chi intervention decreases attention bias to drug cues in individuals with methamphetamine use disorder.

Background: Mind-body exercise is used for the rehabilitation of individuals with methamphetamine use disorder (MUD). Attention bias to substances is an important index of MUD. However, whether a mind-body exercise intervention can decrease attention bias is unclear.Objective: This study aimed to test the effect of a four-week Tai Chi (a Chinese traditional mind-body exercise) exercise program on the attention bias of individuals with MUD.Methods: Thirty-two men with MUD and without Tai Chi practice experience were recruited and randomly assigned to either a Tai Chi exercise group or a control group. The Tai Chi group received four-week Tai Chi training, while the control group engaged in daily exercise (including radio gymnastics and Jianxincao, two kinds of free-hand exercises). During a drug-related Stroop task, participants were instructed to respond to the color of the word ignoring the word type (drug-related or neutral words). The reaction time and d' (the index of sensitivity) were measured.Results: The participants showed attention bias to substance cues; the reaction time was slower for drug-related words than for neutral words (p < .05). After the Tai Chi intervention, the Tai Chi group showed a faster reaction time (ps < .05) and a smaller d' (ps < .05) than the baseline across all the word types. In contrast, the control group showed no differences (ps > .05).Conclusion: Four-week Tai Chi intervention reduced sensitivity and attentional bias to drug-related cues in individuals with MUD, suggesting that mind-body exercise might enhance recovery from MUD via attention control.

It is never as good the second time around: Brain areas involved in salience processing habituate during repeated drug cue exposure in treatment engaged abstinent methamphetamine and opioid users.

The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.

A mindfulness-based, stress and coping model of craving in methamphetamine users.

There is increasing interest in the role of mindfulness and mindfulness-based interventions to optimize recovery from a substance use disorder (SUD). However, relatively little is known about the theory-based psychological and social pathways whereby mindfulness could have beneficial effects for managing a chronic, relapsing SUD. Informed by Revised Stress and Coping Theory, the present cross-sectional study examined affective, cognitive, and social pathways whereby mindfulness is associated with lower methamphetamine craving. A total of 161 HIV-positive, methamphetamine-using sexual minority men completed a screening visit for a randomized controlled trial. Using a hybrid structural equation model, we examined pathways whereby mindfulness is associated with lower methamphetamine craving. We found that greater mindfulness was directly associated with lower negative affect and higher positive affect as well as indirectly associated with less methamphetamine craving. Interestingly, the indirect association between mindfulness and methamphetamine craving appeared to be uniquely attributable to positive affect. Only positive affect was indirectly associated with lower methamphetamine craving via higher positive re-appraisal coping and greater self-efficacy for managing triggers for methamphetamine use. Methamphetamine craving was supported by moderate associations with greater substance use severity and more frequent methamphetamine use. These findings support the role of mindfulness in cultivating positive affect, which could be crucial to build the capacity of individuals to manage methamphetamine craving as a chronic stressor that threatens recovery from SUD.

Lack of longitudinal changes in cognition in individuals with methamphetamine use disorder during the first 6 weeks after commencing treatment.

Background: Methamphetamine use disorder (MUD) associates with cognitive impulsivity deficits. However, few studies have examined longitudinal changes in cognition, and it remains unclear if deficits resolve during early recovery.Objectives: To compare: (1) cognitive function of individuals with MUD at treatment onset and six-weeks later with controls tested over the same period; (2) cognitive changes in MUD-individuals who remained abstinent versus relapsed.Method: We recruited 108 participants meeting DSM-IV-TR criteria for methamphetamine dependence (81 males) and 50 demographically matched controls (38 males); 77 methamphetamine- dependent participants (59 males) and 48 controls (36 males) were retained at follow-up. We administered response inhibition, delay discounting and uncertainty-based decision-making tests at both endpoints. Relapse was defined as methamphetamine concentrations >0.4 ng/mg at follow-up in hair toxicology.Results: We found a significant time-by-group interaction on uncertainty-based decision-making (effect size: η2 = .05), although post-hoc tests to disentangle this interaction yielded inconclusive results (p-range = .14-.40; BF10-range = 0.43-1.67). There were no significant time-by-group interactions on response inhibition or delay discounting, with the former likely a null effect (η2-interaction = .003 and .02; BFincl = 0.23 and 0.71). There were no significant differences in cognitive recovery between individuals who maintained abstinence (n = 12) versus relapsed (n = 65) (η2-range = .003-.04), although evidence was inconclusive toward whether findings reflected true null effects (BFincl-range = 0.33-0.75).Conclusion: We did not find evidence that MUD-related cognitive impulsivity deficits improve beyond practice effects over 6 weeks. Findings do not support previous, albeit conflicting, evidence of early recovery of cognitive deficits in MUD.

Methamphetamine seeking after prolonged abstinence is associated with activated projections from anterior intralaminar nucleus of thalamus to dorsolateral striatum in female rats.

Methamphetamine (Meth) seeking progressively increases after cessation from drug self-administration (incubation of Meth craving). We have previously shown that both dorsomedial and dorsolateral striatum (DMS and DLS) play critical roles in this incubation in male rats. Moreover, our recent anatomical tracing study examined afferent projections into DMS and demonstrated a novel role of projections from anterior intralaminar nucleus of thalamus (AIT) to DMS in incubation of Meth craving in male rats. Here we investigated projection-specific activation of afferent glutamate projections into DLS associated with incubated Meth seeking in female rats. We trained female rats to self-administer Meth (6-h/d for 10 d). On abstinence day 12, we injected cholera toxin subunit B (CTb, a retrograde tracer) unilaterally into DLS. On abstinence day 26, we tested rats for relapse to Meth seeking and measured Fos (a neuronal activity marker), and double-labeling of CTb and Fos in anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, basolateral amygdala, AIT, and parafascicular nuclei of thalamus. We observed neuronal activation in both cortical and thalamic regions associated with incubated Meth seeking. At the circuit level, AIT➔DLS projections were strongly activated, followed by other corticostriatal projections. Overall our results suggest that AIT to DLS may play a role in Meth seeking after prolonged abstinence in female rats.

Pharmacological Treatment of Methamphetamine/Amphetamine Dependence: A Systematic Review.

BACKGROUND: Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions. METHODS: We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use. RESULTS: Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use. CONCLUSIONS: No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.

Expression of miR-133a-5p and ROCK2 in Heart in Methamphetamine-Induced Rats and Intervention of Rhynchophylline.

INTRODUCTION: Rhynchophylline, as a traditional Chinese medicine, was used for the treatment of drug addiction. OBJECTIVE: To investigate miRNAs expression profile in the rat hearts of methamphetamine dependence and the intervention mechanisms of rhynchophylline. MATERIALS AND METHODS: This study detected the expression profile of miRNAs in the methamphetamine-induced rat hearts by microarray and verified the expression of miR-133a-5P and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) protein. RESULTS: After conditioned place preference training, methamphetamine significantly increased the time spent in the drug-paired compartment, while rhynchophylline and MK-801 could reduce the time. Cluster analysis results of miRNAs showed that compared with the control group, the expression of miR-133a-5p in methamphetamine-induced rat hearts was decreased significantly; rhynchophylline could significantly increase the expression of miR-133a-5p. The result was verified by real-time polymerase chain reaction. The results of target gene predictive software and related research showed that ROCK2 protein may be the target gene of miR-133a-5p. The immunohistochemistry results of heart tissues showed that the expression of ROCK2 protein was significantly upregulated in the methamphetamine group and downregulate in the rhynchophylline group; the difference between the MK-801 group and the methamphetamine group was not significant. The result of western blot was consistent with the immunohistochemistry. CONCLUSION: The active ingredient of Chinese herbal medicine rhynchophylline can effectively inhibit the formation of methamphetamine-dependent conditional place preference (CPP) effect in rats to some extent. MiR-133a-5p may participate in the cardioprotective effects of CPP rats by targeting ROCK2.

Assessing the impacts of daily Cannabis versus alcohol and methamphetamines on young Australians in youth AOD treatment.

BACKGROUND: Cannabis is the most widely used illicit substance by Australian young people, including those engaged with youth alcohol and other drug (AOD) systems. While recreational cannabis use in young people may be a developmental activity for some, for others, this usage becomes regular and be associated with poorer long term outcomes. This study reports on the rates of cannabis use and co-existing psychosocial complexity factors in the Youth Needs Census (2013 and 2016) where workers report on all clients in the youth AOD system, a cohort considered highly vulnerable. METHODS: Data was examined for two rounds of data collection for the Youth Needs Census, including 823 youth AOD service engaged young people in 2016 and 1000 AOD service engaged young people in 2013, to identify usage rates, psychosocial outcomes, and changes over time. RESULTS: Daily use of cannabis alone significantly exceeded daily usage rates for methamphetamines, alcohol, and cannabis used alongside other substances. Daily cannabis use was significantly associated with mental health problems, employment problems, education problems, family problems, and housing problems. Daily cannabis use was associated with most psychosocial complexity factors to the same extent as daily methamphetamine use and daily alcohol use, with daily cannabis users only showing lower incidence of the drug-related harm measure. Notably, daily cannabis use also increased from 2013 (47.5%) to 2016 (54.2%). CONCLUSIONS: It is imperative that the number of individuals using cannabis is considered alongside the severity of harm when assessing the social impact of this substance. Within cannabis users engaged with the youth AOD system, who often have high levels of psychosocial complexity, cannabis is used daily by a large proportion of these youths and may play a role in negatively impacting their lives.

Moment-by-Moment in Women's Recovery (MMWR): Mindfulness-based intervention effects on residential substance use disorder treatment retention in a randomized controlled trial.

In this study we test the efficacy of Moment-by-Moment in Women's Recovery (MMWR), a mindfulness-based intervention adapted to support women with substance use disorder (SUD) while in residential treatment. We use a parallel-group randomized controlled trial with a time-matched psychoeducation control to test MMWR effects on residential treatment retention. We used clinical staff-determined residential site discharge status and discharge date from the SUD treatment site record to determine retention. We tested for study group differences in retention defined as time to treatment non-completion without improvement (i.e., patient left treatment before completion of the treatment plan and made little or no progress toward achieving treatment goals based on clinical team determination), as well as differences in self-report of study intervention mechanisms of action (i.e., mindfulness, perceived stress, distress tolerance, emotion regulation, distress, affect, and drug and alcohol craving). The analytic timeframe for the survival analysis was from study intervention start date to 150 days later. The sample (N = 200) was female, majority amphetamine/methamphetamine users (76%), Hispanic (58%), with a history of incarceration (62%). By the 150-day analytic endpoint, the sample had 74 (37%) treatment Completers, 42 (21%) still In-residence, 26 (13%) Non-completers with satisfactory progress, and 58 (29%) Non-completers without satisfactory progress. Survival analysis of the intent-to-treat sample showed the risk of non-completion without improvement was lower in MMWR as compared to the control group (adjusted hazard ratio = 0.42, 95% CI: 0.16-1.08, p = .07). Both groups improved on select self-reported mechanism measure scores at immediate post-intervention, but only in the MMWR group did class attendance (dosage) have a large-size correlation with improved mindfulness (r = .61, p < .01), distress tolerance (r = 0.55, p < .01) and positive affect (r = 0.52, p < .01) scores. The hazard ratio for retention was of medium-to-large effect size, suggesting the clinical relevance of adding MMWR to an all-women's, ethnoracially diverse, SUD residential treatment center. An extended curriculum may be helpful considering the protective benefits of class attendance on psychological health indicators.

Increased demand for amphetamine treatment in rural Australia.

BACKGROUND: A substantial increase in substance treatment episodes for methamphetamine problems suggests characteristics of the treatment population could have changed and that targeted treatment programs are required. To determine who methamphetamine treatment should be designed for this study has two aims. First, to empirically describe changes in amphetamine treatment presentations to a rural NSW drug and alcohol treatment agency over time. Second, to examine how these characteristics may affect the likelihood of being treated for amphetamines compared to other drugs. METHOD: The Australian Alcohol and Other Drug Treatment Services National Minimum Data Set (AODTS-NMDS) containing closed treatment episodes from a single agency from three time periods was used. Characteristics of people receiving amphetamine treatments in these three periods were compared and the effects of these characteristics on the odds of being treated for amphetamine were estimated using a logistic regression model. The characteristics utilised in the analysis include age, sex, Indigenous status, usual accommodation, living arrangement, source of referral and source of income. RESULTS: The proportion of amphetamine treatment episodes doubled from 2006/2007 to 2015/2016 and overtook alcohol as the most commonly treated principal drug of concern. The estimated proportion of amphetamine treatments showed an increment across all ages and for men and women. It was found that younger people, women, people in temporary accommodation or homeless, people who were self-referred and people whose main source of income was not through employment are more likely to be treated for amphetamine use. CONCLUSION: Significant changes over time in the age, sex and Indigenous status of people receiving treatment for amphetamine as the principal drug of concern requires service delivery to match demand from younger people, particularly women; and Indigenous people. The needs and preferences for treatment of younger women who use amphetamine will be important factors in treatment planning service providers who are more used to providing treatment for young men who use cannabis and older men who use alcohol. Further research on women's experiences in treatment and outcomes would be useful for informing treatment practices.

Omega-3 decreases D1 and D2 receptors expression in the prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats.

Amphetamine (AMPH) abuse is a serious public health problem due to the high addictive potential of this drug, whose use is related to severe brain neurotoxicity and memory impairments. So far, therapies for psychostimulant addiction have had limited efficacy. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have shown beneficial influences on the prevention and treatment of several diseases that affect the central nervous system. Here, we assessed the influence of fish oil (FO), which is rich in n-3 PUFA, on withdrawal and relapse symptoms following re-exposure to AMPH. Male Wistar rats received d,l-AMPH or vehicle in the conditioned place preference (CPP) paradigm for 14 days. Then, half of each experimental group was treated with FO (3 g/kg, p.o.) for 14 days. Subsequently, animals were re-exposed to AMPH-CPP for three additional days, in order to assess relapse behavior. Our findings have evidenced that FO prevented relapse induced by AMPH reconditioning. While FO prevented AMPH-induced oxidative damages in the prefrontal cortex, molecular assays allowed us to observe that it was also able to modulate dopaminergic cascade markers (DAT, TH, VMAT-2, D1R and D2R) in the same brain area, thus preventing AMPH-induced molecular changes. To the most of our knowledge, this is the first study to show a natural alternative tool which is able to prevent psychostimulant relapse following drug withdrawal. This non-invasive and healthy nutraceutical may be considered as an adjuvant treatment in detoxification clinics.

Oxytocin-enhanced motivational interviewing group therapy for methamphetamine use disorder in men who have sex with men: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of methamphetamine use disorder (MUD) in the United States has risen dramatically in the past four decades and is concentrated in populations such as men who have sex with men (MSM). Despite the public health consequences of MUD, there are no FDA-approved psychopharmacological treatments. Psychosocial treatment alone has been shown to reduce methamphetamine use, but high attrition rates limit treatment efficacy. Promising findings from animal models of MUD using exogenous oxytocin, a social neuropeptide, have set the stage for translational work. Along with unique anti-addiction effects, oxytocin holds a primary role in enhancing social salience and modulating stress. In humans, oxytocin administration, combined with evidence-based psychosocial interventions, may act synergistically to improve addiction treatment outcomes and improve retention rates in current MUD treatment. METHODS/DESIGN: We are conducting a randomized, double-blind, placebo-controlled trial of oxytocin-enhanced motivational interviewing group therapy (MIGT). Oxytocin or placebo 40 IU is administered intranasally in conjunction with six, weekly MIGT sessions. We will recruit 50 MSM, initiating treatment for MUD from specialized community health programs in San Francisco, CA, USA. Individuals will be randomized (1:1) to receive six, weekly sessions of MIGT with or without oxytocin. Our primary outcome is session attendance. Other outcomes of interest include: measures of group cohesion, anxiety, psychophysiology, and stimulant craving and use. DISCUSSION: This will be the first study of oxytocin's effects in humans with MUD. Findings from this novel protocol will attempt to bridge existing animal data with the need for innovative clinical treatments for MUD, inform the growing field of pharmacologically-enhanced psychotherapy, and help to elucidate mechanisms behind oxytocin's potential anti-addiction effects. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02881177 . Registered on 26 August 2016.