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BACKGROUND: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. OBJECTIVES: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD. METHODS: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment. RESULTS: Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity. CONCLUSIONS: Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.

BackgroundEscalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analogue Risk Task (BART), a laboratory test of decision-making under uncertainty. The BART presents a series of choices with progressively higher stakes-greater risk of loss and greater potential monetary reward. This research aimed to clarify whether impaired behavioral updating contributes to maladaptive performance on the BART.MethodsTwo groups (28 drug-abstinent participants with MUD and 16 healthy control participants) were compared on BART performance. Using a computational model, we deconstructed behavior into risk-taking and behavioral updating. A subset of participants (22 MUD, 15 healthy control) underwent [18F]fallypride positron emission tomography scans to measure dopamine D2-type receptor availability (BPND) in the striatum (caudate and accumbens nuclei and putamen) and the globus pallidus.ResultsParticipants with MUD exhibited slower behavioral updating than the healthy controls (p = 0.0004, d=1.77). BPND in all four bilateral volumes of interest were higher in the healthy control group (ps

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).

Methamphetamine use is surging globally as a cause of morbidity and mortality. Treatment is typically sought in early abstinence, when craving and depressive symptoms are intense, contributing to relapse and poor outcomes. To advance an understanding of this problem and identify therapeutic targets, we conducted a retrospective analysis of brain structure in 89 adults with Methamphetamine Use Disorder who were in early abstinence and 89 healthy controls. Unlike most prior research, the participants did not significantly differ in age, sex and recent use of alcohol and tobacco (p-values ≥ 0.400). We analysed thickness across the entire cerebral cortex by fitting a general linear model to identify differences between groups. Follow-up regressions were performed to determine whether cortical thickness in regions showing group differences was related to craving, measured on a visual analogue scale, or to the Beck Depression Inventory score. Participants in early methamphetamine abstinence (M ± SD = 22.1 ± 25.6 days) exhibited thinner cortex in clusters within bilateral frontal, parietal, temporal, insular, and right cingulate cortices relative to controls (p-values < 0.001, corrected for multiple comparisons). Unlike craving (β = 0.007, p = 0.947), depressive symptoms were positively correlated with cortical thickness across clusters (β = 0.239, p = 0.030) and with thickness in the anterior cingulate cluster (β = 0.246, p = 0.027) in the methamphetamine-dependent group. Inasmuch as anterior cingulate pathology predicts response to antidepressants for Major Depressive Disorder, cingulate structure may also identify patients with Methamphetamine Use Disorder who can benefit from antidepressant medication.

The Addictions Neuroclinical Assessment (ANA) was proposed as a neuroscience-informed clinical framework to understand heterogeneity in addiction encompassing dysfunction in three domains: incentive salience, negative emotionality, and executive functions. The ANA has been validated in the alcohol field but has not been extended to other substances. Thus, the objective of the current study was to replicate and extend the ANA framework to methamphetamine use disorder. Non-treatment seeking individuals (N = 185) who reported regular methamphetamine use completed a deep phenotyping battery comprising self-report and behavioral measures that assessed methamphetamine craving and emotional withdrawal symptoms, mood and anxiety symptomatology, risk-taking behaviors, working memory, attention, and impulsivity. Factor analytic techniques were used in an iterative manner to derive latent factors that explained biobehavioral variation in the sample. The relationship between factor scores and demographic and clinical indicators of methamphetamine use were examined to assess the construct validity of the latent factors. Deep phenotyping combined with factor analytic techniques implicated three intercorrelated neurofunctional domains that map on to the proposed ANA domains: incentive salience, negative emotionality, and executive function. Each of the domains were associated with demographic and clinical indicators of methamphetamine use providing initial support for their construct validity. The ANA framework holds promise for explaining heterogeneity in addiction by identifying neuroscience-informed phenotypes. Knowledge from the ANA framework may be applied to advance precision medicine and inform medications development for a host of substance use disorders, particularly those with no approved pharmacotherapy such as methamphetamine.

IntroductionDenial, or lack of awareness of problems related to substance misuse, is a common feature of drug use disorders and can affect engagement in treatment and recovery. This study tested for association of denial with severity of symptoms used in the diagnosis of Methamphetamine Dependence.MethodsThis secondary analysis used data from 69 participants (52.2% male) who met criteria for the diagnosis of Methamphetamine Dependence on the Structured Clinical Interview for DSM-IV (SCID). The association between diagnostic severity, determined from a SCID summary score (8 items), and denial, measured by the University of Rhode Island Change Assessment Scale (URICA) Precontemplation score, was tested by Pearson correlation. In post hoc t-tests, participants who differed on individual SCID items were compared on the Precontemplation score. The additional URICA subscales (Contemplation, Maintenance, Action) were also tested on a secondary basis.ResultsSCID summary scores were negatively correlated with URICA Precontemplation scores (P = .003). Post-hoc tests revealed that participants who denied continued methamphetamine use despite persistent or recurrent problems (SCID item 6) had significantly higher Precontemplation scores than those who endorsed these problems (t = 3.066, P = .003). In contrast, positive correlations were observed between diagnostic severity and greater openness/willingness to change on the URICA (eg, Maintenance, r = .26; P = .01).ConclusionsThe findings highlight the importance of a patient's insight regarding their addiction in clinical diagnosis. Because minimizing the impact of methamphetamine use may preclude or delay treatment, it is advised that self-report be supplemented to improve accuracy of diagnosis.

ObjectivesContingency management is a promising intervention for Methamphetamine Use Disorder (MUD).Impaired executive function may decrease adherence to such treatment, but there are few data on whether impairment in executive function predicts treatment outcomes. We therefore evaluated whether baseline performance on tests of executive function predicted treatment response in a trial of contingency management for MUD.MethodsThirty participants with MUD and 23 healthy controls performed the Connors Continuous Performance Task (CPT) and the Trail Making Task. MUD participants then entered an 8-week contingency management trial. Participants were categorized as responders (n=17; no methamphetamine-positive urine tests) or non-responders (n=13; >1 positive test). The Kruskal-Wallis test was used to compare scores in participants with MUD and healthy controls, and in responders versus non-responders.ResultsParticipants withMUD performed worse than controls on the CPT (d-prime) (p=0.012); non-responders performed worse than responders (p = 0.034). Performance of MUD participants did not differ significantly from controls on the Trail Making Task B (time to completion), but variation was high with non-responders performing worse than responders (p=0.013).ConclusionThese findings suggest that tests of executive function at baseline may be useful in predicting treatment response in MUD. Future work in larger samples may ultimately allow a more personalized treatment approach to methamphetamine use disorder.

AimsMethamphetamine 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.DesignParticipants 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.ParticipantsParticipants 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).SettingAll study procedures took place in South Africa between August 2016 and May 2018.MeasurementsA 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.FindingsAfter 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

Introduction and aimsAs South Africa, especially the Western Cape Province, faces an epidemic of methamphetamine use disorder, therapeutic approaches suited to the South African context are needed. This secondary analysis assessed retention and methamphetamine abstinence outcomes in response to an 8-week pilot contingency management (CM) intervention trial of neural correlates of methamphetamine abstinence, exploring sociodemographic and clinical differences between responders and non-responders.Design and methodsResearch participants provided thrice-weekly monitored urine samples, which were analysed by qualitative radioimmunoassay. The primary outcome for this analysis was therapeutic response, defined as abstinence from methamphetamine (≥23 of 24 possible methamphetamine-negative urine samples).ResultsData from 30 adults living in Cape Town, South Africa (34 ± 6.1 years of age, mean age ± SD, 21 men) were included. Sixty-three percent (12 men) were responders. In bivariate comparisons, baseline measurements showed fewer responders reported monthly household income ≥25 000+ South African Rand (ZAR; ~USD $1880; vs. ZAR

BackgroundIndividuals with substance use disorders exhibit maladaptive decision-making on the Iowa Gambling Task (IGT), which involves selecting from card decks differing in the magnitudes of rewards, and the frequency and magnitude of losses. We investigated whether baseline IGT performance could predict responses to contingency management (CM) by treatment-seeking individuals with methamphetamine use disorder (MA Use Disorder) in Cape Town, South Africa.MethodsTwenty-nine individuals with MA Use Disorder underwent an 8-week, escalating reinforcement, voucher-based CM treatment in a study on the suitability of CM therapy for the South African context. Along with 20 healthy control participants, they performed a computerized version of the IGT before starting CM treatment. Seventeen participants maintained abstinence from methamphetamine throughout the trial (full responders), and 12 had an incomplete response (partial responders). Performance on the IGT was scored for magnitude effect (selection of large immediate rewards with high long-term loss) and for frequency effect (preference for frequent rewards and avoidance of frequent losses). Group differences were investigated using linear mixed-effect modeling.ResultsPartial responders made more selections from decks providing large, immediate rewards and long-term losses than healthy controls [p = 0.038, g = -0.77 (-1.09: -0.44)]. Full responders showed a greater, nonsignificant preference for frequent rewards and aversion to frequent losses than partial responders [p = 0.054, g = -0.63 (-0.95: -0.29)].ConclusionsA predilection for choices based on the size and immediacy of reward may reflect a cognitive strategy that works against CM. Pretesting with a decision-making task, such as the IGT, may help in matching cognitive therapies to clients with MA Use Disorder.

BackgroundThe 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/designWe 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.DiscussionThis 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 registrationClinicalTrials.gov, ID: NCT02881177 . Registered on 26 August 2016.