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Background and Aims: A 12-week placebo-controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial evaluated the effects of extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo., Design: This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT-2 network trial., Setting: The parent ADAPT-2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States., Participants: This analysis includes 403 people with MA use disorder who participated in the ADAPT-2 CTN trial., Intervention and Comparator: NTX + BUPN was compared with placebo over the course of the trial., Measurement: MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post-treatment follow-up., Findings: Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI), 0.09%-17.9%, P = 0.038] during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%-41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA-negative by a total of 11.4% (95% CI, 4.1%-18.6%, P = 0.002) over all 12 weeks. The 12-week increase among participants on NTX + BUPN was significantly greater-by 15.8% (95% CI, 4.5%-27.0%, P = 0.006)-than the increase among those on placebo., Conclusion: For people with methamphetamine (MA) use disorder receiving treatment with extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks., (© 2024 Society for the Study of Addiction.)

Background: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder., Methods: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles., Discussion: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022., (© 2024. The Author(s).)

This study aims to determine whether performance on the Iowa Gambling Task (IGT), a simulation of risk-taking when faced with loss, is associated with greater frequency of methamphetamine (MA) use and challenges reducing or stopping MA use. The parent mSTUDY is a Los Angeles County-based longitudinal study of substance use and HIV risk in predominately Black/African American and Latinx people assigned male at birth who have sex with men. The IGT was offered for a limited timeframe to mSTUDY participants, of whom 192 consented to and completed this one-time task. Separate random intercept binary logistic regressions tested whether the IGT total score and subscore for Blocks 4 and 5 (last 40 card draws) were associated with the outcomes, testing positive for MA in urine and self-reported inability to control or cease MA use in the past 6 months. Separate random intercept ordered logistic regressions tested whether IGT total score and subscore were associated with self-reported frequency of MA use in past 6 months. Higher IGT subscores for Blocks 4 and 5 (lower risk-taking) were associated with lower odds of testing MA-positive (adjusted odds ratio, AOR = 0.97, 95% CI [0.95, 0.99], p = .025) and less frequent MA use in the past 6 months ( AOR = 0.96, 95% CI [0.94, 0.99], p = .006). Higher IGT total scores (lower risk-taking) were also associated with less frequent MA use ( AOR = 0.99, 95% CI [0.97, 0.99], p = .038). Findings from this analysis suggest that IGT performance may be a useful indicator of MA use severity in nontreatment-seeking people. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

There are limited quantitative studies describing the association between meth use in the context of male-male sexual partnerships and PrEP care engagement. We assessed the longitudinal relationship between individual and partnership level meth use with inconsistent PrEP engagement among young gay, bisexual and other men who have sex with men (GBMSM) in Los Angeles. The primary exposure was meth use at the partnership level with a ternary variable (neither partner nor participant used meth, either used meth, or both used meth). Generalized estimating equations were used to assess odds of inconsistent PrEP engagement at different levels of partner-participant meth use, adjusting for age at visit, number of recent male partners and partner intimacy. Among inconsistent PrEP engagement, 61% (n = 84, vs. 79.5%, n = 346 continuous) reported that neither they nor their partner used meth, 22% (n = 31, vs. 18%, n = 56) reported that either partner or participant used meth and 17% (n = 24, vs. 8%, n = 33) reported that both partner and participant used meth (P < 0.01). There were increased odds of inconsistent PrEP engagement when both partner and participant reported meth use (aOR: 3.82; 95%CI: 1.83-7.99) and when either partner or participant reported meth use (aOR: 2.46; 95%CI: 1.28-4.75). Meth use plays an important role in consistent PrEP engagement among GBMSM in mSTUDY. PrEP users who use meth with partners may benefit from integrated interventions addressing both meth use and PrEP engagement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Methamphetamine use is highly prevalent among men who have sex with men (MSM), but knowledge of the long-term dynamics, and how they are affected by substance use treatment, is limited. This study aimed to describe trajectories of methamphetamine use among MSM, and to evaluate the impact of treatment for any kind of substance use on frequency of methamphetamine use., Methods: This analysis used data from a cohort of MSM in Los Angeles, CA, who participated in semi-annual study visits from 2014 to 2022. The study characterized trajectories of methamphetamine use using a continuous time multistate Markov model with three states. States were defined using self-reported frequency of methamphetamine use in the past six months: frequent (daily), occasional (weekly or less), and never. The model estimated the association between receiving treatment for any kind of substance use and changes in state of frequency of methamphetamine use., Results: This analysis included 2348 study visits among 285 individuals who were followed-up for an average of 4.4 years. Among participants who were in the frequent use state, 65 % (n = 26) of those who were receiving any kind of substance use treatment at a study visit had reduced their methamphetamine use at their next visit, compared to 33 % (n = 95) of those who were not receiving treatment. Controlling for age, race/ethnicity, and HIV-status, those who reported receiving current treatment for substance use were more likely to transition from occasional to no use (HR: 1.63, 95 % CI: 1.10-2.42) and frequent to occasional use (HR: 4.25, 95 % CI: 2.11-8.59) in comparison to those who did not report receiving current treatment for substance use., Conclusions: Findings from this dynamic modeling study provide a new method for assessing longitudinal methamphetamine use outcomes and add important evidence outside of clinical trials that substance use treatment may reduce methamphetamine use., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Inc.)

Background: Methamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW., Methods: Data come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses., Results: MSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04)., Conclusions: Findings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials., Competing Interests: Declaration of Competing Interest Drs. Kidd and Smiley reports no financial relationships with commercial interests. Dr. Coffin directs an NIH-funded trial that receives donated tenofovir-emtricitabine from Gilead Sciences. Dr. Carmody has been a consultant for Alkermes. Dr. Levin receives grant support from the NIDA, SAMHSA, US World Meds and research support from Aelis Pharmaceuticals. She also receives medication from Indivior for research. In addition, Dr. Levin served as a nonpaid member of a Scientific Advisory Board for Alkermes, Indivior, Novartis, Teva, and US WorldMeds; receives royalties from APA Publishing; and is a consultant to Major League Baseball. Dr. Nunes has served as an uncompensated consultant to Alkermes, Indivior, and Camurus, and as an investigator on NIH-funded studies that received in-kind medication from Alkermes, Indivior, and Braeburn/Camurus, and in-kind digital therapeutics from Pear Therapeutics and Chess Health. Dr. Shoptaw receives clinical support for his research from Gilead Sciences, Alkermes and Indivior. He also consults with Aelis Pharmaceuticals. Dr. Shoptaw is also the Editor-in-Chief at Drug and Alcohol Dependence, an Elsevier journal., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial., Methods: The multi-site ADAPT-2 study used a randomized, double blind, sequential parallel comparison design to evaluate treatment with extended-release injectable NTX (380 mg every 3 weeks) combined with once-daily oral extended-release BUP (450 mg/day) vs matching injectable and oral placebo in outpatients with moderate or severe MA use disorder. The study assessed smoking outcomes, based on self-reported timeline followback (TLFB) data, twice/week for 13 weeks., Results: Of the 403 participants in the ADAPT-2 trial, 290 reported being current cigarette smokers (71.9 %). The study found significant differences (p's < 0.0001) for each smoking outcome indicating greater change in the proportion of nonsmoking days, number of cigarettes smoked per week, and consecutive nonsmoking days, all favoring the group receiving NTX-BUP versus placebo., Conclusions: NTX-BUP was associated with significant reductions in self-reported cigarette smoking in the context of concurrent treatment for MA use disorder. These off-target medication effects warrant prospective investigation using biochemically confirmed measures of smoking abstinence. The development of NTX-BUP as a co-addiction treatment strategy has a potential for high public health impact., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Madhukar Trivedi: Within the past 12 months, Dr. Trivedi has provided consulting services to Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc, Compass Pathfinder Limited, Daiichi Sankyo Inc, GH Research Limited, Heading Health Inc, Janssen, Legion Health Inc, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc, Merck Sharp & Dhome LLC, Naki Health, Ltd., Neurocrine Biosciences Inc, Otsuka American Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization Inc, Praxis Precision Medicines Inc, Relmada Therapeutics, Inc, SAGE Therapeutics, Signant Health, Sparian Biosciences Inc, Takeda Pharmaceutical Company Ltd, and WebMD. He sits on the Scientific Advisory Board of Alto Neuroscience Inc, Cerebral Inc., Compass Pathfinder Limited, Heading Health, GreenLight VitalSign6 Inc, Legion Health Inc, and Merck Sharp & Dohme Corp. He holds stock in Alto Neuroscience Inc, Cerebral Inc, Circular Genomics Inc, GreenLight VitalSign6 Inc, Legion Health Inc. Additionally, he has received editorial compensation from American Psychiatric Association, and Oxford University Press. Dr. Thomas Carmody: Dr. Carmody has served as a consultant for Alkermes, Inc. Dr. Stephen Shoptaw: Dr. Shoptaw has received clinical supplies for this research from Alkermes, Inc., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: Socio-cultural (gender) and biological (sex)-based differences contribute to psychostimulant susceptibility, potentially affecting treatment responsiveness among women with methamphetamine use disorder (MUD). The aims were to measure (i) how women with MUD independently and compared with men respond to treatment versus placebo and (ii) among women, how the hormonal method of contraception (HMC) affects treatment responsiveness., Design: This was a secondary analysis of ADAPT-2, a randomized, double-blind, placebo-controlled, multicenter, two-stage sequential parallel comparison design trial., Setting: United States., Participants: This study comprised 126 women (403 total participants); average age = 40.1 years (standard deviation = 9.6) with moderate to severe MUD., Interventions: Interventions were combination intramuscular naltrexone (380 mg/3 weeks) and oral bupropion (450 mg daily) versus placebo., Measurements: Treatment response was measured using a minimum of three of four negative methamphetamine urine drug tests during the last 2 weeks of each stage; treatment effect was the difference between weighted treatment responses of each stage., Findings: At baseline, women used methamphetamine intravenously fewer days than men [15.4 versus 23.1% days, P = 0.050, difference = -7.7, 95% confidence interval (CI) = -15.0 to -0.3] and more women than men had anxiety (59.5 versus 47.6%, P = 0.027, difference = 11.9%, 95% CI = 1.5 to 22.3%). Of 113 (89.7%) women capable of pregnancy, 31 (27.4%) used HMC. In Stage 1 29% and Stage 2 5.6% of women on treatment had a response compared with 3.2% and 0% on placebo, respectively. A treatment effect was found independently for females and males (P < 0.001); with no between-gender treatment effect (0.144 females versus 0.100 males; P = 0.363, difference = 0.044, 95% CI = -0.050 to 0.137). Treatment effect did not differ by HMC use (0.156 HMC versus 0.128 none; P = 0.769, difference = 0.028, 95% CI -0.157 to 0.212)., Conclusions: Women with methamphetamine use disorder receiving combined intramuscular naltrexone and oral bupropion treatment achieve greater treatment response than placebo. Treatment effect does not differ by HMC., (© 2023 Society for the Study of Addiction.)

Methamphetamine (MA) use is associated with HIV transmission among men who have sex with men (MSM) and lapses in medication adherence. Contingency Management (CM) is effective in reducing MA use, but studies of CM to support adherence to HIV prevention or treatment are limited. We conducted a pilot trial of a CM intervention to reduce MA use and improve PrEP/ART adherence among MSM prescribed a tenofovir (TFV)-based regimen for HIV prevention or treatment. Participants were randomly assigned to receive escalating incentives for either MA abstinence or TFV adherence (based on point-of-care urine testing), and to a monitoring schedule of either 2 or 3 visits/week for 4 weeks. 19 MSM were randomized to either CM for MA use or CM for PrEP/ART adherence (median age: 38; IQR: 28-46) and 15 were living with HIV. Participants attended 95.7% (67/70) of scheduled visits in the 2x/week arm and 74.8% (74/99) in the 3x/week arm. TFV adherence was higher among participants in the TFV adherence arm with 93.5% (n = 72/77) of urine samples positive for TFV, compared to 76.6% (n = 49/64) in the MA abstinence arm (p = 0.007). Participants in the MA abstinence arm had more urine samples negative for MA metabolites (20.3%, n = 13/64) than those receiving CM for TFV adherence (6.5%, n = 5/77; p = 0.021). A CM model for MA abstinence and PrEP/ART adherence using twice-weekly visits and urine testing for MA and TFV for MSM who use MA is feasible and potentially effective as an integrated harm reduction strategy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non-randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2-4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal., (© 2022 Society for the Study of Addiction.)

Decision-making tendencies and spending within cash voucher-based interventions have individually been shown to be related to future abstinence among participants with methamphetamine use disorder (MUD), but less is known of their independent contributions. This study of participants in a contingency management (CM) trial investigated whether decision-making and spending were each associated with future abstinence. Thirty-two outpatients with MUD, predominately male (68%) and mixed ancestry (94%) with a median age of 34 years, participated in an 8-week cash voucher-based CM pilot trial. Prior to commencing the trial, participants completed a computerized Iowa Gambling Task (IGT) to measure decision-making preferences for more frequent rewards and longer term gains of greater magnitude . Spending and abstinence of participants were tracked over the duration of the trial. In a secondary analysis, time-lagged counting process Cox Proportional Hazard models were conducted. Baseline decision-making, characterized by a preference for frequent rewards, was associated with a greater likelihood of future spending, Hazard Ratio; HR = 1.13 [1.06: 1.21]. Avoidance of short-term rewards to realize longer term, higher magnitude rewards, and spending at the prior visit were each associated with abstinence on the trial, HR = 1.12 [1.03: 1.22] and HR = 1.32 [1.08: 1.61], respectively. Controlling for decision-making, spending, and cumulative abstinence, prior abstinence remained the largest predictor of future abstinence, HR = 3.85 [2.88: 5.16]. Decision-making tendencies and spending are correlated yet independently associated with abstinence reinforcement in CM. Findings highlight the opportunity for behavioral treatment programs to tailor program structures to individual-specific characteristics. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Social genomics has demonstrated altered inflammatory and type I interferon (IFN) gene expression among people experiencing chronic social adversity. Adverse social experiences such as discrimination and violence are linked to stimulant misuse and HIV, conditions that dysregulate inflammatory and innate antiviral responses, leading to increased HIV viral replication and risk of chronic diseases., Purpose: We aimed to determine whether methamphetamine (MA) use, unsuppressed HIV viral load (VL) (≥200 c/mL), and experienced intimate partner violence (IPV) (past 12 months) predicted inflammatory and type I IFN gene expression in HIV-positive Black and Latinx men who have sex with men (MSM)., Methods: Participants were 147 HIV-positive Black and Latinx MSM recruited from the mSTUDY, a cohort of 561 MSM aged 18-45 in Los Angeles, CA, of whom half are HIV-positive and substance-using. Transcriptomic measures of inflammatory and type I IFN activity were derived from RNA sequencing of peripheral blood mononuclear cells and matched to urine drug tests, VL, and survey data across two time points 12 months apart. Analysis used linear random intercept modeling of MA use, unsuppressed VL, and experienced IPV on inflammatory and type I IFN expression., Results: In adjusted models, MA use predicted 27% upregulated inflammatory and 31% upregulated type I IFN expression; unsuppressed VL predicted 84% upregulated type I IFN but not inflammatory expression; and experienced IPV predicted 31% upregulated inflammatory and 26% upregulated type I IFN expression., Conclusions: In Black and Latinx MSM with HIV, MA use, unsuppressed VL, and experienced IPV predicted upregulated social genomic markers of immune functioning., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Overdose is one of the leading causes of death in the US; however, surveillance data lag considerably from medical examiner determination of the death to reporting in national surveillance reports., Objective: To automate the classification of deaths related to substances in medical examiner data using natural language processing (NLP) and machine learning (ML)., Design, Setting, and Participants: Diagnostic study comparing different natural language processing and machine learning algorithms to identify substances related to overdose in 10 health jurisdictions in the US from January 1, 2020, to December 31, 2020. Unstructured text from 35 433 medical examiner and coroners' death records was examined., Exposures: Text from each case was manually classified to a substance that was related to the death. Three feature representation methods were used and compared: text frequency-inverse document frequency (TF-IDF), global vectors for word representations (GloVe), and concept unique identifier (CUI) embeddings. Several ML algorithms were trained and best models were selected based on F-scores. The best models were tested on a hold-out test set and results were reported with 95% CIs., Main Outcomes and Measures: Text data from death certificates were classified as any opioid, fentanyl, alcohol, cocaine, methamphetamine, heroin, prescription opioid, and an aggregate of other substances. Diagnostic metrics and 95% CIs were calculated for each combination of feature extraction method and machine learning classifier., Results: Of 35 433 death records analyzed (decedent median age, 58 years [IQR, 41-72 years]; 24 449 [69%] were male), the most common substances related to deaths included any opioid (5739 [16%]), fentanyl (4758 [13%]), alcohol (2866 [8%]), cocaine (2247 [6%]), methamphetamine (1876 [5%]), heroin (1613 [5%]), prescription opioids (1197 [3%]), and any benzodiazepine (1076 [3%]). The CUI embeddings had similar or better diagnostic metrics compared with word embeddings and TF-IDF for all substances except alcohol. ML classifiers had perfect or near perfect performance in classifying deaths related to any opioids, heroin, fentanyl, prescription opioids, methamphetamine, cocaine, and alcohol. Classification of benzodiazepines was suboptimal using all 3 feature extraction methods., Conclusions and Relevance: In this diagnostic study, NLP/ML algorithms demonstrated excellent diagnostic performance at classifying substances related to overdoses. These algorithms should be integrated into workflows to decrease the lag time in reporting overdose surveillance data.

Background: Methamphetamine use, sexual risk behaviors, and depression contribute to ongoing human immunodeficiency virus (HIV) and sexually transmitted infection (STI) disparities among men who have sex with men (MSM). The relative contributions of these effects longitudinally are not well understood., Methods: This analysis used visit-level data from a longitudinal cohort of MSM, half with HIV, in Los Angeles, CA. From August 2014 to March 2020, participants completed follow-up visits every 6 months and underwent testing for rectal gonorrhea/chlamydia (GC/CT) and completed questionnaires including depressive symptoms, number of receptive anal intercourse (RAI) partners, and methamphetamine use. Path analysis with structural equation modeling using concurrent and lagged covariates was used to identify relative contributions of methamphetamine use and depression on number of RAI partners and rectal GC/CT across time., Results: Five hundred fifty-seven MSM with up to 6 visits (3 years) were included for a total of 2437 observations. Methamphetamine use and depressive symptoms were positively associated with number of RAI partners (β = 0.28, P < 0.001; β = 0.33, P = 0.018, respectively), which was positively associated with rectal GC/CT (β = 0.02, P < 0.001). When stratified by HIV status, depressive symptoms were positively associated with RAI partners for HIV-negative MSM (β = 0.50, P = 0.007) but were not associated for MSM living with HIV (β = 0.12, P = 0.57). Methamphetamine use was positively associated with RAI partners in both strata., Conclusions: Factors and patterns, which contribute to risk behaviors associated with rectal GC/CT, may differ by HIV status. Our findings demonstrate the importance of combined treatment and prevention efforts that link screening and treatment of stimulant use and depression with STI prevention and treatment., Competing Interests: Conflict of Interest: None declared., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: During the COVID-19 pandemic in 2020, concerns were raised about the potential impact of pandemic-related social distancing measures on existing health disparities among sexual and gender minority (SGM) young adults, including HIV transmission risk and intimate partner violence (IPV). Another concern was the potential for increased methamphetamine use during the pandemic, which is a known risk factor for HIV transmission and IPV., Methods: The present analysis examines the impact of COVID-19 social distancing (social distancing and quarantining) and methamphetamine use on HIV risk and IPV in a combined dataset from 3 cohort studies of SGM young adults (two in Los Angeles and one in Chicago) from May 2020 to April 2021 (n = 1142). Bivariate analyses and multivariable logistic regressions were estimated., Results: The median age was 26. All participants were assigned male at birth and most participants were men (93.8%). The largest racial groups were Hispanic/Latinx (44.6%) and Black (29.0%). In adjusted models methamphetamine use was consistently associated with having a new sex partner, higher numbers of sex partners, and experience of IPV, during the pandemic. Reporting no social distancing and reporting one social distancing behavior, were associated with experience of IPV relative to reporting 2 social distancing behaviors. Social distancing was not associated with sexual risk behavior or Pre-exposure Prophylaxis use., Conclusions: SGM young adults live at the intersection of multiple vulnerabilities during the COVID-19 pandemic. Addiction services, HIV prevention services, and violence support services should be prepared to support young adult SGM needs, particularly those who use methamphetamine., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To assess the severity of methamphetamine use among methadone maintenance treatment (MMT) patients in Vietnam with opioid use disorder and concurrent methamphetamine use, and to identify risk factors associated with higher severity of methamphetamine use., Methods: We used survey data and medical record abstractions from 428 people with opioid use disorder who also use methamphetamine while partaking in methadone treatment in five clinics in Hanoi, Vietnam. We used multinomial logistic regression to assess other risk factors and problems associated with high methamphetamine use severity., Results: Those who reported injecting heroin in the past 3 months (AOR = 4.05, 95% CI [1.30, 12.55], p = 0.02), having a longer history of lifetime heroin use (AOR = 1.13, 95% CI [1.03, 1.24], p < 0.01), and having higher cravings (AOR = 1.97, 95% CI [1.31, 2.98], p < 0.01) and fatigue (AOR = 1.25, 95% CI [0.96, 1.61], p = 0.09) related to methamphetamine withdrawal had greater odds of high methamphetamine use severity. One of five clinics had a significantly higher percentage of methamphetamine use severity than others., Conclusion: Successful MMT in patients with opioid use disorder in Vietnam may additionally require methamphetamine-focused screening and intervention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Substance use decreases the likelihood of achieving undetectable HIV viremia; however, the comparative effects by drug have not been fully described. In this study, we compare the effects of methamphetamine use versus other drugs on viremia in sexual minority men on antiretroviral therapy (ART)., Methods: HIV-positive participants currently on ART (N = 230) were selected from an ongoing cohort of diverse young sexual minority men (mSTUDY) enrolled from August 2014 to May 2018. Substance use and sociodemographic factors associated with viremia outcomes were assessed using ordinal regression analysis with generalized estimating equations. Viremia outcomes were grouped as undetectable (<20 copies/mL), low level suppressed (21-200 copies/mL), or not suppressed (>200 copies/mL)., Results: The prevalence of drug use across 825 study visits was 73 %, with methamphetamine use most prevalent (50 %). After adjusting for unstable housing and ART adherence, methamphetamine use, either alone (adjusted OR = 1.87; 95 % CI 1.03-3.40) or with other drugs (adjusted OR = 1.82; 95 % CI 1.12-2.95), was associated with higher odds of increasing viremia compared to no drug use. Other drug use excluding methamphetamine did not show a similar association (adjusted OR = 1.29; 95 % CI 0.80-2.09). Among our study population, nearly half the instances of viremia could be reduced if methamphetamine was discontinued (attributable fraction = 46 %; 95 % CI 3-71 %)., Conclusions: Methamphetamine use, either alone or in combination with other drugs, is associated with failure of viral suppression among sexual minority men on ART independent of adherence and sociodemographic factors. This accounts for nearly half of the observed instances of unsuppressed viremia in this study., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied., Methods: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses., Results: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial., Conclusions: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Prevalence of methamphetamine (meth) injection and associated human immunodeficiency virus (HIV) risks among men who have sex with men (MSM) are unclear., Methods: A total of 532 MSM completed 1880 mSTUDY study visits between August 2014 and June 2018 in Los Angeles, California. Assessments every 6 months included computer-assisted self-interviews and testing for sexually transmitted infections. Analyses by person and across visits adjusted for repeated measures., Results: Of 532 participants, 51% (n = 276) reported meth use (past 6 months). Across 1880 visits, mutually exclusive substance use categories were as follows: 5% meth injection (5%), meth use without injection (33%), other substance use excluding meth (36%), and no substance use (26%). Comparisons across these categories respectively found that meth injectors reported higher prevalence of new sex partners (89%, 70%, 68%, and 51%, respectively), more were HIV positive (83%, 65%, 34%, and 50%), fewer were virally suppressed (53%, 48%, 61%, and 67%), and more had sexually transmitted infections (31%, 22%, 15%, and 15% (all P <.01)., Conclusions: Among the young MSM reporting meth injection in this Los Angeles cohort, elevated risks of acquiring or transmitting HIV suggest that they contribute significantly to sustaining the local HIV epidemic. Preventing transition to injection use has potential for HIV prevention., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Methamphetamine (MA) triggers neuroinflammation and medications that counteract MA-induced neuroinflammation may reduce MA-induced neurodegeneration and improve neurocognition and treatment outcomes in MA use disorder. We performed a randomized, placebo-controlled trial to determine the safety and efficacy of ibudilast (IBUD), a phosphodiesterase inhibitor that reduces neuroinflammation, for the treatment of MA use disorder. Treatment-seeking volunteers with MA use disorder were randomly assigned to receive 12 weeks of IBUD 50 mg twice daily (N = 64) or placebo (N = 61) with medication management counseling. Participants visited the outpatient research clinic twice weekly to provide urine specimens for drug screens and undergo study assessments. The primary outcome was end of treatment MA-abstinence (EOTA) during weeks 11 and 12 of treatment. Serum IBUID levels were measured for IBUD participants during week 3 of treatment. There was no difference in EOTA for IBUD (14%) versus placebo (16%, p > 0.05). There was no correlation between serum IBUD levels and MA use during treatment and mean IBUD levels for participants with (mean = 51.3, SD = 20.3) and without (mean = 54.7, SD = 33.0, p = 0.70) EOTA. IBUD was well tolerated. IBUD did not facilitate MA abstinence in this outpatient trial. Whether targeting neuroinflammation, either with IBUD in other subgroups of MA users or clinical trial designs, or with other anti-inflammatory medications, is an effective strategy for treating MA use disorder is not clear. Graphical Abstract The proportion of urine drug screens negative for methamphetamine (MA) during the two week lead-in period (weeks -2 and - 1) and the 12 week medication treatment period (weeks 1-12) for ibudilast versus placebo.

Aims: Methamphetamine Use Disorder is prevalent in South Africa. This analysis uses data from a contingency management (CM) pilot study in South Africa to replicate and expand on a U.S.-based study showing that CM voucher spending was associated with drug abstinence behavior., Design: Participants with methamphetamine-use disorder were enrolled in an 8-week CM trial requiring thrice weekly visits and received cash vouchers in exchange for stimulant-negative urines at each visit., Participants: Participants were 33 treatment-seeking individuals with methamphetamine use disorder including 22 men (66.7%) and 11 women (33.3%) with a mean age of 34 years (S.D. = 7.7). Participants reported using methamphetamine for a mean of 11.7 years (S.D. = 4.9)., Setting: All study procedures took place in South Africa between August 2016 and May 2018., Measurements: A time-lagged counting process Cox Proportional Hazards model for recurrent event survival analysis examined the relationship between frequency of and participant-categorized type of CM expenditures (hedonic, utilitarian, consumable or durable) and drug abstinence., Findings: After controlling for severity of baseline methamphetamine use and accumulated CM earnings (proxied by cumulative negative urines), those spending CM earnings at a previous visit ("spenders") were more likely to produce stimulant-negative urine samples subsequently, compared to those who did not ("savers") [OR = 1.23, CI = 1.08-1.53, p = .002]. There were significantly more cumulative stimulant-negative results among spenders vs. savers, p < .001, although cumulative spending did not significantly predict abstinence once spending in the prior time period was controlled for, suggesting a recency effect tied to the underlying spending mechanism. When extending the original analyses to look at the effect of spending on current abstinence, controlling only for recent abstinence (rather than cumulative abstinence), spending was no longer a significant predictor. Spending type did not affect methamphetamine abstinence. Qualitative results suggest spending CM vouchers may support social reintegration over the course of the trial., Conclusions: Abstinence outcomes are a function of CM spending in both the U.S. and South Africa. Findings of a significant relationship between contingency management spending and subsequent stimulant-negative urine samples across geographic locations provide guidance toward future work in optimizing CM efficacy., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Preclinical studies suggest that the non-selective phosphodiesterase inhibitor, Ibudilast (IBUD) may contribute to the treatment of methamphetamine (METH) use disorder through the attenuation of METH-induced inflammatory markers such as adhesion molecules, sICAM-1 and sVCAM-1, and cytokines, IL-6 and TNF-α., Objective: The present study aimed to test whether treatment with IBUD can attenuate peripheral markers of inflammation during a METH challenge in an inpatient clinical trial of 11 patients., Methods: This trial followed a randomized, within-subjects crossover design where participants received a METH challenge, during which five participants were treated with placebo then with IBUD, while the remaining six participants were treated with IBUD prior to placebo. Mixed effects regression modeled changes in peripheral markers of inflammation-sICAM-1, sVCAM-1, TNF-α, IL-6, MIF, and cathepsin D-by treatment condition, with measurements at baseline, 60 min post-METH infusion, and 360 min post-METH infusion., Results: While on placebo, sICAM-1, sVCAM-1, and cathepsin D significantly increased by 60 min post-METH infusion, while IL-6 significantly increased 360 min post-METH infusion. Treatment with IBUD significantly reduced METH-induced levels of sICAM-1, sVCAM-1, and cathepsin D at 60 min post-METH infusion., Conclusions: Our findings demonstrate that IBUD attenuated acute pro-inflammatory effects of METH administration, which may have implications for treatment of METH use disorder., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: In the era of HIV treatment as prevention (TasP), evidence-based interventions that optimize viral suppression among people who use stimulants such as methamphetamine are needed to improve health outcomes and reduce onward transmission risk. We tested the efficacy of positive affect intervention delivered during community-based contingency management (CM) for reducing viral load in sexual minority men living with HIV who use methamphetamine., Methods: Conducted in San Francisco, this Phase II randomized controlled trial tested the efficacy of a positive affect intervention for boosting and extending the effectiveness of community-based CM for stimulant abstinence to achieve more durable reductions in HIV viral load. From 2013 to 2017, 110 sexual minority men living with HIV who had biologically confirmed, recent methamphetamine use were randomized to receive a positive affect intervention (n = 55) or attention-control condition (n = 55). All individual positive affect intervention and attention-control sessions were delivered during three months of community-based CM where participants received financial incentives for stimulant abstinence. The 5-session positive affect intervention was designed to provide skills for managing stimulant withdrawal symptoms as well as sensitize individuals to natural sources of reward. The attention-control condition consisted of neutral writing exercises and self-report measures., Results: Men randomized to the positive affect intervention displayed significantly lower log 10 HIV viral load at six, twelve and fifteen months compared to those in the attention-control condition. Men in the positive affect intervention also had significantly lower risk of at least one unsuppressed HIV RNA (≥200 copies/mL) over the 15-month follow-up. There were concurrent, statistically significant intervention-related increases in positive affect as well as decreases in the self-reported frequency of stimulant use at six and twelve months., Conclusions: Delivering a positive affect intervention during community-based CM with sexual minority men who use methamphetamine achieved durable and clinically meaningful reductions in HIV viral load that were paralleled by increases in positive affect and decreases in stimulant use. Further clinical research is needed to determine the effectiveness of integrative, behavioural interventions for optimizing the clinical and public health benefits of TasP in sexual minority men who use stimulants such as methamphetamine., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Contingency management (CM) is an evidence-based intervention providing rewards in exchange for biomarkers that confirm abstinence from stimulants such as methamphetamine. We tested the efficacy of a positive affect intervention designed to boost the effectiveness of CM with HIV-positive, methamphetamine-using sexual minority men., Methods: This attention-matched, randomized controlled trial of a positive affect intervention delivered during CM was registered on www.clinicaltrials.gov (NCT01926184). In total, 110 HIV-positive sexual minority men with biologically confirmed, recent methamphetamine use were enrolled. Five individual sessions of a positive affect intervention (n = 55) or an attention-control condition (n = 55) were delivered during three months of CM. Secondary outcomes examined over the 3-month intervention period included: 1) psychological processes relevant to affect regulation (i.e., positive affect, negative affect, and mindfulness); 2) methamphetamine craving; 3) self-reported stimulant use (past 3 months); and 4) cumulative number of urine samples that were non-reactive for stimulants (i.e., methamphetamine and cocaine) during CM., Results: Those randomized to the positive affect intervention reported significant increases in positive affect during individual sessions and increases in mindfulness over the 3-month intervention period. Intervention-related improvements in these psychological processes relevant to affect regulation were paralleled by concurrent decreases in methamphetamine craving and self-reported stimulant use over the 3-month intervention period., Conclusions: Delivering a positive affect intervention may improve affect regulation as well as reduce methamphetamine craving and stimulant use during CM with HIV-positive, methamphetamine-using sexual minority men., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Methamphetamine use increases the risk of HIV-1 infection among seronegative users and can exacerbate disease progression in HIV-positive users. The biological mechanisms underlying these associations remain unclear. In this cross-sectional pilot study, we examine the associations between recent methamphetamine use and inflammation in the rectal mucosa and peripheral blood compartments in HIV-1 seropositive and seronegative men who have sex with men., Methods: HIV-seronegative and HIV-seropositive men who have sex with men participants were enrolled (N = 24). Recent methamphetamine use was determined by urine drug screen. Cytokines were quantified using multiplex arrays from collected plasma and rectal sponge samples, and peripheral blood T-cell activation was assessed by flow cytometry., Results: Methamphetamine use was associated with consistently increased rectal inflammatory cytokines, specifically interleukin-6 and tumor necrosis factor-alpha, regardless of HIV-1 serostatus in this pilot study. This association was significant after adjusting for age, HIV-serostatus, and receptive anal intercourse frequency using regression analysis. Similar increases were not uniformly observed in peripheral blood., Conclusions: Methamphetamine use is associated with increased local mucosal inflammatory cytokine production. These findings may help explain the increased HIV-1 risk seen in methamphetamine users and contribute to increased inflammation among HIV-seropositive users.

Objective: Microbial translocation and monocyte activation predict mortality in treated HIV. We examined whether substance use independently contributes to these pathophysiologic processes., Design: Cross-sectional study at baseline for a randomized controlled trial., Methods: HIV-positive, methamphetamine-using MSM with undetectable HIV viral load (less than 40 copies/ml) were enrolled. We examined if plasma biomarkers of monocyte activation and intestinal barrier integrity were associated with the following: reactive urine toxicology results (Tox+) for stimulants (i.e., methamphetamine or cocaine) and substance use severity measured by the Addiction Severity Index. Multiple linear regression models adjusted for age, antiretroviral therapy regimen, CD4 T-cell count, interleukin-6, and alcohol use severity., Results: The sample of 84 virally suppressed MSM had a median CD4 T-cell count of 645 cells/μl. Those who were Tox+ for stimulants displayed higher soluble CD14 (sCD14) levels (2087 versus 1801 ng/ml; P = 0.009), and this difference remained significant after adjusting for covariates (standardized beta = 0.23, P = 0.026). Greater substance use severity was also independently associated with higher sCD14 after adjusting for covariates (standardized beta = 0.29, P = 0.013). Being Tox+ for stimulants and substance use severity were not associated with soluble CD163 (sCD163) or intestinal fatty acid binding protein (iFABP) levels (P > 0.05)., Conclusions: Monocyte activation is one plausible mechanism by which stimulant use may increase clinical HIV progression.

Background: Inattention is a deficit related to instilling abstinence from methamphetamine (MA) dependence. This study aimed to determine whether ibudilast (IB; 50mg bid) improves attentional abilities compared to placebo during early abstinence from MA dependence., Methods: Attention was assessed in 11 MA-dependent non-treatment seeking participants in a phase IB safety-interaction trial. The Conners' Continuous Performance Test-II (CPT-II), a measure of sustained attention and response inhibition, was administered at baseline and on day 22, 48h post a MA challenge under placebo (P; n=6) or IB 50mg bid (n=5). Group differences were compared using Mann-Whitney U Tests. Groups were similar at baseline in premorbid intellectual functioning, attention deficit hyperactivity symptom scores, impulsivity ratings, and education level, but differed in age. Demographically corrected T-scores for CPT-II performances were utilized., Results: Although no group differences in sustained attention existed at baseline, at follow-up, the IB group (Mdn=44.4) showed reduced variability in response times compared with the P group (Mdn=69.9), U=0.00, z=-2.74, p=.006, r=.83. The IB group (Mdn=45.8) also gave fewer perseverative responses than the P group (Mdn=67.0), U=2.00, z=-2.50, p=.01, r=.75. No other significant differences were observed., Conclusions: Findings suggest that IB may have a protective effect on sustained attention during early abstinence from MA dependence. This may guide thinking about mechanism of action should IB demonstrate efficacy as a treatment for MA dependence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Rationale: Reductions in cue-induced craving and subjective response to drugs of abuse are commonly used as initial outcome measures when testing novel medications for the treatment of addiction. Yet neither the relationship between these two measures at the individual level nor the moderating effects of pharmacotherapies on this relationship has been examined., Objective: This secondary data analysis sought to examine (1) the predictive relationship between cue-induced craving and subsequent acute subjective response to methamphetamine (MA) and (2) whether the opioid-receptor antagonist naltrexone moderated this association in a sample of non-treatment-seeking individuals who met DSM-IV criteria for MA use disorder (abuse or dependence)., Methods: Participants (n = 30) completed two 4-day medication regimens (oral naltrexone 50 mg or placebo, in a randomized, counterbalanced, and double-blind fashion). On day 4 of each medication regimen, participants completed a cue-reactivity paradigm followed by intravenous MA administration. Methamphetamine craving was assessed after the cue-reactivity paradigm, and subjective response to MA was assessed during MA infusion., Results: Cue-induced craving for MA was positively associated with post-infusion subjective MA effects, including positive (i.e., stimulation, good effects, feel drug, high), negative (i.e., anxious and depressed), and craving-related (i.e., want more, would like access to drug, crave) responses. Naltrexone, vs. placebo, significantly reduced the association between cue-induced craving and positive subjective response to MA., Conclusions: The findings indicate that naltrexone moderates the predictive relationship between cue-induced craving and positive subjective effects of MA, thereby suggesting a behavioral mechanism by which naltrexone may be efficacious in treating MA use disorder.

Background: Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial., Methods: Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events., Results: Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast., Conclusions: Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence.

Background: Contingency management (CM) is an evidence-based intervention providing tangible rewards as positive reinforcement for abstinence from stimulants such as methamphetamine. Integrative approaches targeting affect regulation could boost the effectiveness of CM in community-based settings and optimize HIV/AIDS prevention efforts., Methods/design: This randomized controlled trial with HIV-positive, methamphetamine-using men who have sex with men (MSM) is examining the efficacy of a 5-session, individually delivered positive affect regulation intervention - Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS). ARTEMIS is designed to sensitize individuals to non-drug-related sources of reward as well as assist with managing depression and other symptoms of stimulant withdrawal during CM. HIV-positive, methamphetamine-using MSM who are enrolled in a community-based, 12-week CM program are randomized to receive ARTEMIS or an attention-matched control condition. Follow-up assessments are conducted at 3, 6, 12, and 15 months after enrollment in CM. Four peripheral venous blood samples are collected over the 15-month follow-up with specimen banking for planned biomarker sub-studies. The primary outcome is mean HIV viral load. Secondary outcomes include: sustained HIV viral suppression, T-helper cell count, psychological adjustment, stimulant use, and potentially amplified transmission risk behavior., Discussion: Implementation of this randomized controlled trial highlights the importance of delineating boundaries between research activities and community-based service provision. It also provides insights into best practices for integrating the distinct agendas of academic and community partners in clinical research. This trial is currently enrolling and data collection is anticipated to be completed in September of 2018., Trial Registration: This trial was registered on clinicaltrials.gov ( NCT01926184 ) on August 16, 2013.

Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Fifty-two non-treatment-seeking methamphetamine-using men who have sex with men were enrolled in Project Tech Support, an open-label pilot study to evaluate whether exposure to theory-based [social support theory (SST), social cognitive theory (SCT), and health belief model (HBM)] text messages could promote reductions in HIV sexual risk behaviors and/or methamphetamine use. Multivariable analyses revealed that increased relative exposure to HBM or SCT (vs. SST) text messages was associated with significant reductions in the number of HIV serodiscordant unprotected (i.e., without a condom) anal sex partners, engagement in sex for money and/or drugs, and frequency of recent methamphetamine use; additionally, increased relative exposure to HBM (vs. SCT or SST) messages was uniquely associated with reductions in the overall number of non-primary anal sex partners (all p ≤ 0.05, two-tailed). Pilot data demonstrated that text messages based on the principles of HBM and SCT reduced sentinel HIV risk and drug use behaviors in active methamphetamine users.

Aims: Two previous randomized trials found an effect for bupropion in reducing methamphetamine use in the subgroup with lower frequency of methamphetamine use at baseline. This study aimed to replicate these results by comparing bupropion versus placebo in methamphetamine-dependent participants with less than daily methamphetamine use at baseline., Methods: Methamphetamine-dependent volunteers reporting methamphetamine use on ≤29 of past 30 days were randomized to bupropion 150 mg twice daily (n = 41) or placebo (n = 43) and out-patient counseling for 12 weeks. The primary outcome was the proportion achieving end-of-treatment (EOT) methamphetamine abstinence (weeks 11 and 12) for bupropion versus placebo. A post-hoc analysis compared EOT abstinence by medication adherence assessed via plasma bupropion/hydroxybupropion level., Results: There was no significant difference in EOT abstinence between bupropion (29%, 12 of 41) and placebo (14%, six of 43; P = 0.087). Among participants receiving bupropion, EOT abstinence was significantly higher in participants assessed as medication adherent by plasma bupropion/hydroxybupropion levels (54%, seven of 13) compared to non-adherent participants (18%, five of 28; P = 0.018). Medication adherence by plasma levels was low (32%)., Conclusions: Bupropion may be efficacious for reducing methamphetamine in people with less than daily baseline methamphetamine use, but the evidence remains inconclusive., (© 2014 Society for the Study of Addiction.)

Abstract Among women, methamphetamine (meth) use has been associated with intimate partner violence (IPV); however, few studies have looked at the context of IPV. This qualitative pilot study explored the experiences of meth-using women in Los Angeles County regarding: (1) IPV in their most recent primary relationship; (2) use of contraception and reproductive health services; and (3) meth use during pregnancy. Participants (n=30) were recruited through community advertising and at three addiction treatment centers to participate in 15-20 minute, semi-structured interviews recorded with handwritten transcripts. The team analyzed transcripts for key themes. Participants reported IPV (n=19, 63%) as recipients (50%), perpetrators (40%), and/or both (27%), occurring mainly during active meth use or withdrawal. While most (n=25) continued meth use during at least one pregnancy, some (n=5, 17%) identified pregnancy as a motivation to quit or reduce use, suggesting an opportunity for intervention. Though most women knew about free and low-cost reproductive health services, few accessed them, with 33% citing aspects of meth use itself as a barrier. One-third (45/133) of reported pregnancies were terminated by abortion. Most women (67%) began using before age 18, suggesting need for screening and intervention among adolescents.

This study compared outcomes in methamphetamine use and sexual risk behaviors from a modified gay-specific, cognitive behavioral therapy (GCBT) combined with a low-cost contingency management (CM; [GCBT+CM]) intervention to prior findings from clinical trials of the original GCBT. Effect sizes for primary outcomes were compared using meta analysis. Comparisons of effect sizes at end of treatment showed the modified GCBT+CM produced significantly fewer consecutive weeks of methamphetamine abstinence (-0.44, CI: -0.79, -0.09) and fewer male sexual partners (-0.36, CI: -0.71, -0.02) than the first trial of GCBT, and more days of methamphetamine use (0.35, CI: 0.02, 0.68) than the second trial of GCBT. At 26-week follow-up, the modified GCBT+CM produced greater effects in reducing the number of male sexual partners (-0.54, CI: -0.89, -0.19; -0.51, CI: -0.84, -0.18). The original GCBT produced more and mostly short-term beneficial drug use outcomes, though sexual behavior changes consistently favored the modified GCBT+CM. On balance, most benefits are retained with the modified GCBT+CM intervention., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

An evidence-based gay-specific cognitive behavioral therapy (GCBT) intervention for methamphetamine-using gay and bisexual men was adapted for use in a community-based setting, thereby moving research into practice. The 48-session, 16-week GCBT intervention was revised to 24 sessions requiring 8 weeks and renamed Getting Off: A Behavioral Treatment Intervention for Gay and Bisexual Male Methamphetamine Users. GCBT was modified for implementation within the limited resources and capacity of community-based organizations while also retaining drug use and HIV risk reduction outcomes. Since 2007, Getting Off has been sustained with public health funding at the community site and has been adopted by multiple community-based sites.

Background: It is particularly important to survey substance use trends in populations most impacted by the consequences of substance use. Men who have sex with men (MSM) exhibit rates of methamphetamine and other substance use that exceeds those observed among other populations in the United States. Such substance use has been associated with numerous negative health sequelae., Methods: An outreach program performed street encounters with 5599 unique substance-using MSM from January 1, 2008 through December 31, 2011 to collect data on self-reported sociodemographics and recent substance use. Data were aggregated into six-month cohorts for comparisons of recent substance use patterns across time, Results: Participants averaged 33 years of age (SD=8), most were Caucasian/white (47%) or Hispanic/Latino (32%), and the self-reported HIV seroprevalence rate was 13.4%. Across cohorts, reported use of alcohol (range=91-93%), marijuana (range=36-46%), and/or methamphetamine (range=23-27%) was common; prevalence of amyl nitrite (max=14%), ecstasy (max=12%), powder cocaine (max=8%) and/or crack cocaine (max=4%) use, although less common, were still elevated relative to the United States general population., Conclusions: Methamphetamine and other substance use remained common among substance-using MSM, demonstrating the need for continued substance use interventions geared toward this high-risk population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: This secondary analysis of data from a randomized controlled trial tested two behavioral economics mechanisms (substitutability and delay discounting) to explain outcomes using contingency management (CM) for methamphetamine dependence. Frequency and purchase type (hedonic/utilitarian and consumable/durable) of CM payments were also examined., Methods: A total of 82 methamphetamine-dependent gay/bisexual men randomly assigned to conditions delivering CM received monetary vouchers in exchange for stimulant-negative urine samples in a 16-week trial requiring thrice weekly visits (Shoptaw et al., 2005). At any visit participants could redeem vouchers for goods. A time-lagged counting process Cox Proportional Hazards model for recurrent event survival analysis examined aspects of the frequency and type of these CM purchases., Results: After controlling for severity of baseline methamphetamine use and accumulated CM wealth, as measured by cumulative successful earning days, participants who redeemed CM earnings at any visit ("spenders") were significantly more likely to produce stimulant-negative urine samples in the subsequent visit, compared with those who did not redeem ("savers") 1.011* [1.005, 1.017], Z = 3.43, p < .001., Conclusions: Findings support the economic concept of substitutability of CM purchases and explain trial outcomes as a function of frequency of CM purchases rather than frequency or accumulated total CM earnings. Promotion of frequent purchases in incentive-based programs should facilitate substitution for the perceived value of methamphetamine and improve abstinence outcomes., (PsycINFO Database Record (c) 2013 APA, all rights reserved.)

Purpose: To perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents., Methods: Nineteen adolescents with methamphetamine abuse (n = 2) or dependence (n = 17) were randomly assigned to bupropion SR 150 mg twice daily or placebo for 8 weeks with outpatient substance abuse counseling., Results: Bupropion was well-tolerated except for one female in the bupropion group who was hospitalized for suicidal ideation during a methamphetamine relapse. Adolescents receiving bupropion and females provided significantly fewer methamphetamine-free urine tests compared to participants receiving placebo (p = .043) and males (p = .005) respectively., Conclusions: Results do not support the feasibility of additional trials of bupropion for adolescent methamphetamine abuse/dependence. Future studies should investigate the influence of gender on adolescent methamphetamine abuse and treatment outcomes., (Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction and Aims: Cigarette smoking occurs frequently among individuals with methamphetamine (MA) dependence. Preclinical and clinical evidence has suggested that the common co-abuse of MA and cigarettes represents a pharmacologically meaningful pattern., Methods: The present study is a secondary analysis of a randomised, placebo-controlled trial of bupropion treatment for MA dependence (bupropion n = 36; placebo n = 37). A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non-smokers. Among smokers, relations between cigarettes smoked and MA use were assessed., Results: Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition. In the placebo condition, increased cigarette use was associated with an increased probability of MA use during the same time period. This effect was not observed in the bupropion condition., Discussion and Conclusions: Initial smoking status did not impact treatment outcomes. Among smokers, results suggest that bupropion may dissociate cigarette and MA use. The effect was modest and a precise pharmacological mechanism remains elusive. Cholinergic systems may be relevant for MA use outcomes. Future studies should continue to assess the role of smoking in MA treatment outcomes., (© 2012 Australasian Professional Society on Alcohol and other Drugs.)

Treatment responses of placebo groups in addiction medicine trials have important implications for research methodology and clinical practice, however studies examining placebo group responses in addiction medicine are scarce. Extant data suggest the importance of early treatment responsiveness for long-term outcomes. Among methamphetamine-(MA) dependent individuals randomized to placebo pill plus behavioral support conditions in pharmacotherapy development trials, we hypothesized that immediate abstinence would be a necessary but insufficient predictor for end-of-trial (EOT) abstinence. The study is a secondary analysis of participants (n = 184; 36% female) in the placebo condition of three randomized, placebo-controlled methamphetamine dependence pharmacotherapy trials. Receiver operating characteristic (ROC) curve analyses assessed the predictive power of initial abstinence, assessed by thrice weekly urine samples, for EOT abstinence. Sixty percent of individuals with complete abstinence in the first two weeks of treatment were abstinent at EOT, while 18% of people who failed to meet this standard were abstinent at EOT. Early response was related to retention at EOT and 12-month follow-up. Findings suggest that the inability to achieve at least three MA negative screenings in the first two weeks is associated with greater than 90% likelihood of treatment failure. A third week of screening added minimally to the prediction of EOT outcomes. The prediction of treatment failure was more precise than the prediction of treatment success. The absence of a clinical response in the first two weeks of treatment among participants in the placebo group signals high risk of treatment failure. The majority of information regarding response in the placebo group from a 12-week trial is obtained early in the trial.

Text-messaging interventions present a novel approach for targeting high-risk men who have sex with men (MSM) who may not respond to or may be difficult to reach for face-to-face or site-based interventions. Project Tech Support (N = 52) was an open label pilot study testing the feasibility and utility of a text-messaging intervention to reduce methamphetamine use and high-risk sexual behaviors among out-of-treatment MSM. Participants in the two-week intervention received social support and health education text messages transmitted in real-time. At follow-up, there were significant decreases in frequency of methamphetamine use and unprotected sex while on methamphetamine (both p < 0.01), and a significant increase in self-reported abstinence from methamphetamine use (13.3 % vs. 48.9 %; p < 0.001). Additionally, participants reported reductions of unprotected anal intercourse with HIV-positive partners (p < 0.01); with HIV-negative partners, participants reported fewer insertive and receptive episodes (both p < 0.05). Findings demonstrate that text messaging is a promising intervention for reaching and potentially changing HIV high-risk behaviors among out-of-treatment, methamphetamine-using MSM.

Background: Two clinical trials have shown efficacy for bupropion in treating methamphetamine (MA) dependence among those with moderate baseline MA use. However, treatment response is highly variable and it is unclear what duration of treatment is necessary to determine if maintaining the treatment course is indicated or if discontinuation or augmentation is appropriate. The present study assessed the relationship among early bupropion treatment response for moderate MA users and end-of-treatment (EOT) abstinence. These data provide estimates of the duration of treatment and the degree of responsiveness required to persist in bupropion treatment., Methods: Participants with moderate baseline MA use in the bupropion condition of two randomized double-blind placebo controlled trials were included. The relationship between early treatment response and EOT outcomes was assessed with Receiver Operating Characteristic (ROC) curves., Results: With thrice weekly urine drug testing, excellent predictive power was established in the first two weeks of treatment. The inability to achieve at least three MA negative samples in the first two weeks is associated with greater than 90% likelihood of treatment failure. More closely approximating clinical settings, once-weekly testing featured reliable predictive power within three weeks, suggesting that the failure to produce at least two clean samples in the first three weekly visits confers high risk of treatment failure., Discussion: The findings provide preliminary evidence to guide clinical decisions for moderate MA users receiving bupropion. The results are consistent with data from the smoking cessation literature and may highlight the importance of early response in addiction treatment., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Frequency of pretreatment methamphetamine (MA) use is an important predictor of outcomes of treatment for MA dependence. Preclinical studies suggest females self-administer more MA than males, but few clinical studies have examined potential sex differences in the frequency of MA use. Estrogen increases expression of brain-derived neurotrophic factor (BDNF), which has effects on MA-induced striatal dopamine release and protects against MA-induced neurotoxicity., Objective: We examined potential effects of sex, the Val66Met polymorphism in BDNF, and their interaction on frequency of MA use among 60 Caucasian MA-dependent volunteers screening for a clinical trial., Methods: Data was taken from 60 Caucasian MA-dependent volunteers screening for a clinical trial., Results: Females reported significantly more pretreatment days with MA use in the past 30 days than males. There was a significant interaction between sex and BDNF Val66Met, with the highest frequency of MA use among females with Val/Val genotype., Conclusions: These results, although preliminary, add to the literature documenting sexual dimorphism in response to stimulants, including MA, and suggest a potential biological mechanism involving BDNF that might contribute to these differences. Additional research characterizing the biological basis of altered response to MA among females is warranted., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

Aims: To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence., Design: A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only)., Setting: Three substance abuse treatment clinics: two in-patient, one out-patient., Participants: Treatment-seeking, methamphetamine-dependent adults (n = 120)., Measurements: Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial., Findings: No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events., Conclusions: The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

Background: Methamphetamine use is associated with HIV acquisition and transmission among men who have sex with men (MSM). Contingency management (CM), providing positive reinforcement for drug abstinence and withholding reinforcement when abstinence is not demonstrated, may facilitate reduced methamphetamine use and sexual risk. We compared CM as a stand-alone intervention to a minimal intervention control to assess the feasibility of conducting a larger, more definitive trial of CM; to define the frequency of behavioral outcomes to power such a trial; and, to compute preliminary estimates of CM's effectiveness., Methods: We randomly assigned 127 MSM from Seattle, WA who use methamphetamine to receive a 12-week CM intervention (n = 70) or referral to community resources (n = 57)., Results: Retention at 24 weeks was 84%. Comparing consecutive study visits, non-concordant UAI declined significantly in both study arms. During the intervention, CM and control participants were comparably likely to provide urine samples containing methamphetamine (adjusted relative risk [aRR] = 1.09; 95%CI: 0.71, 1.56) and to report non-concordant UAI (aRR = 0.80; 95%CI: 0.47, 1.35). However, during post-intervention follow-up, CM participants were somewhat more likely to provide urine samples containing methamphetamine than control participants (aRR = 1.21; 95%CI: 0.95, 1.54, P = 0.11). Compared to control participants, CM participants were significantly more likely to report weekly or more frequent methamphetamine use and use of more than eight quarters of methamphetamine during the intervention and post-intervention periods., Conclusions: While it is possible to enroll and retain MSM who use methamphetamine in a trial of CM conducted outside drug treatment, our data suggest that CM is not likely to have a large, sustained effect on methamphetamine use.

Objective: To compare modafinil to placebo for reducing methamphetamine (MA) use, improving retention, and reducing depressive symptoms and MA cravings. Rates of adverse events and cigarette smoking with modafinil versus placebo were also compared., Methods: Following a 2-week, non-medication lead-in period, 71 treatment-seeking MA-dependent participants were randomly assigned to modafinil (400mg once daily; N=34) or placebo (once daily; N=37) for 12 weeks under double-blind conditions. Participants attended clinic thrice-weekly to provide urine samples analyzed for MA-metabolite, to complete research assessments, and to receive contingency management and weekly cognitive behavioral therapy (CBT) sessions., Results: There were no statistically significant effects for modafinil on MA use, retention, depressive symptoms, or MA cravings in pre-planned analyses. Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high-frequency of MA use (MA use on >18 of past 30 days), but did not reach statistical significance in these small subgroups. Modafinil was safe and well tolerated and did not increase cigarette smoking., Conclusions: Modafinil was no more effective than placebo at 400mg daily in a general sample of MA users. A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high-frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)