The Experts below are selected from a list of 1890 Experts worldwide ranked by ideXlab platform
Igor Grant - One of the best experts on this subject based on the ideXlab platform.
-
sustained attention and vigilance deficits associated with hiv and a history of Methamphetamine Dependence
Drug and Alcohol Dependence, 2020Co-Authors: Nina Pocuca, Robert K. Heaton, Igor Grant, Jared W Young, David A Macqueen, Scott Letendre, Mark A Geyer, William Perry, Arpi MinassianAbstract:Abstract Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is Methamphetamine Dependence (METH). Such Dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, antiretroviral therapy initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; 50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the main and interactive (additive versus synergistic) effects of HIV and history of METH on the sustained attention and vigilance cognitive domain, while controlling for VLS. Methods Participants included 205 (median age = 44 years; 77% males; HIV-/METH- n = 67; HIV+/METH - n = 49; HIV-/METH+ n = 36; HIV+/METH+ n = 53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5-Choice continuous performance tests (CPTs). Results METH participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for Methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV- participants. There was no HIV x METH interaction on sustained attention and vigilance. Conclusions Recent Methamphetamine use among METH people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of antiretroviral therapy, and METH use interventions.
-
sustained attention and vigilance deficits associated with hiv and a history of Methamphetamine Dependence
bioRxiv, 2020Co-Authors: Nina Pocuca, Robert K. Heaton, Igor Grant, Jared W Young, David A Macqueen, Scott Letendre, Mark A Geyer, William Perry, Arpi MinassianAbstract:Abstract Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is Methamphetamine Dependence (METH+). Such Dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, ART initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; ≤50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH+ on the sustained attention and vigilance cognitive domain, while controlling for VLS. Methods Participants included 205 (median age=44 years; 77% males; HIV-/METH- n=67; HIV+/METH - n=49; HIV-/METH+ n=36; HIV+/METH+ n=53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5- Choice continuous performance tests (CPTs). Results METH+ participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for Methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV-participants. There was no HIV x METH interaction on sustained attention and vigilance. Conclusions Recent Methamphetamine use among METH+ people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of ART, and METH use interventions.
-
typologies of positive psychotic symptoms in Methamphetamine Dependence
American Journal on Addictions, 2015Co-Authors: Chad A. Bousman, Rebecca Mcketin, Ian Everall, Hampton J. Atkinson, Erin E Morgan, Richard Burns, Steven Paul Woods, Igor GrantAbstract:Background and Objectives Understanding Methamphetamine associated psychotic (MAP) symptom typologies could aid in identifying individuals at risk of progressing to schizophrenia and guide early intervention.
-
elevated intraindividual variability in Methamphetamine Dependence is associated with poorer everyday functioning
Psychiatry Research-neuroimaging, 2014Co-Authors: Erin E Morgan, Thomas D Marcotte, William Perry, Arpi Minassian, Brook L Henry, Steven Paul Woods, Katie L Doyle, Igor GrantAbstract:Methamphetamine (MA) Dependence is associated with executive dysfunction, but no studies have evaluated MA-related elevations in neurocognitive intraindividual variability (IIV), an expression of cognitive dyscontrol linked to poor daily functioning in populations with frontal systems injury. We examined IIV during a vigilance task in a well-characterized sample of 35 MA-dependent (MA+) and 55 non-MA using comparison participants (MA-) as part of a larger neuropsychological battery that included self-report and performance-based measures of everyday functioning. A mixed model ANOVA was conducted while controlling for covariates, including factors that differed between the groups (e.g., education) and those with conceptual relevance to IIV: mean reaction time, global cognitive performance, and HIV-infection (which was comparable across groups; p=0.32). This analysis revealed significantly elevated IIV among MA+ relative to MA- individuals that was comparable in magnitude across all trial blocks of the vigilance task. Within the MA group, elevated IIV was associated with executive dysfunction, psychomotor slowing, and recency of MA use, as well as poorer automobile driving simulator performance, worse laboratory-based functional skills, and more cognitive complaints. MA-users are vulnerable to IIV elevation, likely due to cognitive dyscontrol, which may increase their risk of real-world problems.
-
HIV and Chronic Methamphetamine Dependence Affect Cerebral Blood Flow
Journal of Neuroimmune Pharmacology, 2011Co-Authors: Beau M. Ances, Mariana Cherner, Igor Grant, Ronald J Ellis, Florin Vaida, Melinda J. Yeh, Christine L. Liang, Carly Gardner, Richard B. BuxtonAbstract:Human immunodeficiency virus (HIV) and Methamphetamine (METH) Dependence are independently associated with neuronal dysfunction. The coupling between cerebral blood flow (CBF) and neuronal activity is the basis of many task-based functional neuroimaging techniques. We examined the interaction between HIV infection and a previous history of METH Dependence on CBF within the lenticular nuclei (LN). Twenty-four HIV−/METH−, eight HIV−/METH+, 24 HIV+/METH−, and 15 HIV+/METH+ participants performed a finger tapping paradigm. A multiple regression analysis of covariance assessed associations and two-way interactions between CBF and HIV serostatus and/or previous history of METH Dependence. HIV+ individuals had a trend towards a lower baseline CBF (−10%, p = 0.07) and greater CBF changes for the functional task (+32%, p = 0.01) than HIV− subjects. Individuals with a previous history of METH Dependence had a lower baseline CBF (−16%, p = 0.007) and greater CBF changes for a functional task (+33%, p = 0.02). However, no interaction existed between HIV serostatus and previous history of METH Dependence for either baseline CBF ( p = 0.53) or CBF changes for a functional task ( p = 0.10). In addition, CBF and volume in the LN were not correlated. A possible additive relationship could exist between HIV infection and a history of METH Dependence on CBF with a previous history of METH Dependence having a larger contribution. Abnormalities in CBF could serve as a surrogate measure for assessing the chronic effects of HIV and previous METH Dependence on brain function.
Walter Ling - One of the best experts on this subject based on the ideXlab platform.
-
double blind placebo controlled evaluation of the prometa protocol for Methamphetamine Dependence
Addiction, 2012Co-Authors: Walter Ling, Steven Shoptaw, Keith G Heinzerling, Maureen Hillhouse, Michelle Anne Bholat, Charles Charuvastra, David Chim, Jeffrey J Annon, Patrick T Dowling, Geetha DoraimaniAbstract: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.
-
randomized placebo controlled trial of bupropion for the treatment of Methamphetamine Dependence
Drug and Alcohol Dependence, 2008Co-Authors: Richard De La Garza, Thomas F. Newton, Steven Shoptaw, Keith G Heinzerling, Erin Rotheramfuller, Trevor Steward, J Wang, Aimee Noelle Swanson, Walter LingAbstract:Abstract Objective To compare bupropion to placebo for reducing Methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA-cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. Methods Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N = 36) or placebo (twice 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 measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions. Results There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA-cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0–2 MA-positive urines), but not heavier (3–6 MA-positive urines) MA use during baseline (OR = 2.81, 95% CI = 1.61–4.93, p p = 0.0002). Conclusion Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light-MA users is warranted.
-
bupropion for the treatment of Methamphetamine Dependence
Neuropsychopharmacology, 2008Co-Authors: Ahmed Elkashef, Edwina V Smith, Francis Vocci, Nora Chiang, Roberta Kahn, Walter Ling, Richard A Rawson, Ann L Anderson, Tyson H Holmes, Valerie PearceAbstract:Bupropion was tested for efficacy in increasing weeks of abstinence in Methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study. One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of Methamphetamine Dependence were consented and enrolled. Seventy-two participants were randomized to placebo and 79 to sustained-release bupropion 150 mg twice daily. Patients were asked to come to the clinic three times per week for assessments, urine drug screens, and 90-min group psychotherapy. The primary outcome was the change in proportion of participants having a Methamphetamine-free week. Secondary outcomes included: urine for quantitative Methamphetamine, self-report of Methamphetamine use, subgroup analyses of balancing factors and comorbid conditions, addiction severity, craving, risk behaviors for HIV, and use of other substances. The generalized estimating equation regression analysis showed that, overall, the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant (p=0.09). Mixed model regression was used to allow adjustment for baseline factors in addition to those measured (site, gender, level of baseline use, and level of symptoms of depression). This subgroup analysis showed that bupropion had a significant effect compared to placebo, among male patients who had a lower level of Methamphetamine use at baseline (p<0.0001). Comorbid depression and attention-deficit/hyperactivity disorder did not change the outcome. These data suggest that bupropion, in combination with behavioral group therapy, was effective for increasing the number of weeks of abstinence in participants with low-to-moderate Methamphetamine Dependence, mainly male patients, regardless of their comorbid condition.
-
randomized placebo controlled trial of baclofen and gabapentin for the treatment of Methamphetamine Dependence
Drug and Alcohol Dependence, 2006Co-Authors: Keith G Heinzerling, Steven Shoptaw, James A Peck, Xiaowei Yang, Juanmei Liu, John M Roll, Walter LingAbstract:Abstract Objective To conduct a 16-week, randomized, placebo-controlled, double-blind trial of two GABAergic medications, baclofen (20 mg tid) and gabapentin (800 mg tid), for the treatment of Methamphetamine Dependence. Methods Adults with Methamphetamine Dependence were randomized to one of three conditions for 16 weeks: baclofen ( n = 25), gabapentin ( n = 26) or placebo ( n = 37). All participants attended clinic thrice weekly to receive study medication and psychosocial counseling, complete study assessments, and provide urine samples. Results No statistically significant main effects for baclofen or gabapentin in reducing Methamphetamine use were observed using a generalized estimating equation (GEE). A significant treatment effect was found in post hoc analyses for baclofen, but not gabapentin, relative to placebo among participants who reported taking a higher percentage of study medication (significant treatment group and medication adherence interaction in GEE model of Methamphetamine use). Conclusions While gabapentin does not appear to be effective in treating Methamphetamine Dependence, baclofen may have a small treatment effect relative to placebo. Future studies evaluating the effectiveness of baclofen and other GABAergic agents for treatment of Methamphetamine may be warranted.
-
randomized placebo controlled trial of sertraline and contingency management for the treatment of Methamphetamine Dependence
Drug and Alcohol Dependence, 2006Co-Authors: Steven Shoptaw, Erin Rotheramfuller, Alice Huber, James A Peck, Xiaowei Yang, Juanmei Liu, Jeff Dang, John M Roll, Benjamin Shapiro, Walter LingAbstract:Abstract Background Methamphetamine Dependence and associated medical and psychiatric concerns are significant public health issues. This project evaluated the efficacy of sertraline (50 mg bid) and contingency management (CM) for the treatment of Methamphetamine Dependence. Method In this randomized, placebo-controlled, double-blind trial, participants completed a 2-week non-medication baseline and were randomized to one of four conditions for 12 weeks: sertraline plus CM (n = 61), sertraline-only (n = 59), matching placebo plus CM (n = 54), or matching placebo-only (n = 55). All participants attended clinic thrice-weekly for data collection, medication dispensing, and relapse prevention groups. Outcomes included Methamphetamine use (urine drug screening and self-reported days of use), retention (length of stay), drug craving (visual analogue scale), and mood symptoms (Beck Depression Inventory). Results No statistically significant main or interaction effects for sertraline or CM in reducing Methamphetamine use were observed using a generalized estimating equation (GEE), although post hoc analyses showed the sertraline-only condition had significantly poorer retention than other conditions (χ2 (3) = 8.40, p Conclusions These data do not demonstrate improved outcomes for sertraline versus placebo for treatment of Methamphetamine Dependence; indeed, they suggest sertraline is contraindicated for Methamphetamine Dependence. Findings provide support for the use of contingency management for treatment of Methamphetamine Dependence.
Steven Shoptaw - One of the best experts on this subject based on the ideXlab platform.
-
varenicline for the treatment of Methamphetamine Dependence
Drug and Alcohol Dependence, 2015Co-Authors: Marisa S Briones, Keith G Heinzerling, Aimee Noelle Swanson, Matthew J Worley, Dustin Z Deyoung, Steven ShoptawAbstract:disorders. The online toolkit addresses the needs of parents who want to receive an EST, but do not have access to a CRAFT therapist. The toolkit consists of six modules addressing different skills. The first module provides an introduction to CRAFT and trains parents how to recognize the signs that their child is currently intoxicated. The Communication module trains parents in seven communication skills. The Roadmap module conducts a functional analysis to help parents outline their child’s pattern of drug use, occasioning situations and reinforcers. The Positive Reinforcement module teaches parents to identify their child’s desirable behaviors and then identify and deliver reinforcers when their child is sober or when a desirable behavior occurs. The Planned Ignoring and Natural Consequences module teaches parents to avoid interaction with their child when he or she is intoxicated and teaches them to allow negative consequences to occur. In the final module, parents will learn when and how to encourage their child to enter treatment. Modules contain videos of a therapist introducing key concepts and parent/child interactions to display the concepts. In addition, there are training exercises throughoutmodules to allow parents to practice skills and receive feedback. The online toolkit is being developed through a partnership with the Treatment Research Institute and Cadence Online, Inc. Conclusions: Modules will be evaluated through focus groups with the goal of evaluating the completed toolkit through randomized, controlled trials. Financial support: P50DA027841 & Cadence Online, Inc.
-
double blind placebo controlled evaluation of the prometa protocol for Methamphetamine Dependence
Addiction, 2012Co-Authors: Walter Ling, Steven Shoptaw, Keith G Heinzerling, Maureen Hillhouse, Michelle Anne Bholat, Charles Charuvastra, David Chim, Jeffrey J Annon, Patrick T Dowling, Geetha DoraimaniAbstract: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.
-
predicting adherence to treatment for Methamphetamine Dependence from neuropsychological and drug use variables
Drug and Alcohol Dependence, 2009Co-Authors: Andy C. Dean, Edythe D. London, Keith G Heinzerling, Aimee Noelle Swanson, Catherine A Sugar, Christina M R Kitchen, Ari Kalechstein, Steven ShoptawAbstract:Although some individuals who abuse Methamphetamine have considerable cognitive deficits, no prior studies have examined whether neurocognitive functioning is associated with outcome of treatment for Methamphetamine Dependence. In an outpatient clinical trial of bupropion combined with cognitive behavioral therapy and contingency management (Shoptaw, S., Heinzerling, K.G., Rotheram-Fuller, E., Steward, T., Wang, J., Swanson, A.N., De La Garza, R., Newton, T., Ling, W., 2008. Randomized, placebo-controlled trial of bupropion for the treatment of Methamphetamine Dependence. Drug Alcohol Depend 96, 222-232.), 60 Methamphetamine-dependent adults completed three tests of reaction time and working memory at baseline. Other variables that were collected at baseline included measures of drug use, mood/psychiatric functioning, employment, social context, legal status, and medical status. We evaluated the relative predictive value of all baseline measures for treatment outcome using Classification and Regression Trees (CART; Breiman, L., Friedman, J.H., Olshen, R.A., Stone, C.J., 1984. Classification and Regression Trees. Wadsworth, Belmont, CA.), a nonparametric statistical technique that produces easily interpretable decision rules for classifying subjects that are particularly useful in clinical settings. Outcome measures were whether or not a participant completed the trial and whether or not most urine tests showed abstinence from Methamphetamine abuse. Urine-verified Methamphetamine abuse at the beginning of the study was the strongest predictor of treatment outcome; two psychosocial measures (e.g., nicotine Dependence and Global Assessment of Functioning) also offered some predictive value. A few reaction time and working memory variables were related to treatment outcome, but these cognitive measures did not significantly aid prediction after adjusting for Methamphetamine usage at the beginning of the study. On the basis of these findings, we recommend that research groups seeking to identify new predictors of treatment outcome compare the predictors to Methamphetamine usage variables to assure that unique predictive power is attained.
-
randomized placebo controlled trial of bupropion for the treatment of Methamphetamine Dependence
Drug and Alcohol Dependence, 2008Co-Authors: Richard De La Garza, Thomas F. Newton, Steven Shoptaw, Keith G Heinzerling, Erin Rotheramfuller, Trevor Steward, J Wang, Aimee Noelle Swanson, Walter LingAbstract:Abstract Objective To compare bupropion to placebo for reducing Methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA-cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. Methods Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N = 36) or placebo (twice 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 measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions. Results There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA-cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0–2 MA-positive urines), but not heavier (3–6 MA-positive urines) MA use during baseline (OR = 2.81, 95% CI = 1.61–4.93, p p = 0.0002). Conclusion Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light-MA users is warranted.
-
randomized placebo controlled trial of baclofen and gabapentin for the treatment of Methamphetamine Dependence
Drug and Alcohol Dependence, 2006Co-Authors: Keith G Heinzerling, Steven Shoptaw, James A Peck, Xiaowei Yang, Juanmei Liu, John M Roll, Walter LingAbstract:Abstract Objective To conduct a 16-week, randomized, placebo-controlled, double-blind trial of two GABAergic medications, baclofen (20 mg tid) and gabapentin (800 mg tid), for the treatment of Methamphetamine Dependence. Methods Adults with Methamphetamine Dependence were randomized to one of three conditions for 16 weeks: baclofen ( n = 25), gabapentin ( n = 26) or placebo ( n = 37). All participants attended clinic thrice weekly to receive study medication and psychosocial counseling, complete study assessments, and provide urine samples. Results No statistically significant main effects for baclofen or gabapentin in reducing Methamphetamine use were observed using a generalized estimating equation (GEE). A significant treatment effect was found in post hoc analyses for baclofen, but not gabapentin, relative to placebo among participants who reported taking a higher percentage of study medication (significant treatment group and medication adherence interaction in GEE model of Methamphetamine use). Conclusions While gabapentin does not appear to be effective in treating Methamphetamine Dependence, baclofen may have a small treatment effect relative to placebo. Future studies evaluating the effectiveness of baclofen and other GABAergic agents for treatment of Methamphetamine may be warranted.
Rebecca Mcketin - One of the best experts on this subject based on the ideXlab platform.
-
A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for Methamphetamine (“ice”) Dependence
Trials, 2019Co-Authors: Rebecca Mcketin, Peter Higgs, Alyna Turner, Brendan Quinn, Gregory Carter, Olivia M Dean, Paul Dietze, Dan I Lubman, Peter J Kelly, Amanda L. BakerAbstract:BackgroundThere are currently no approved pharmacotherapies for managing Methamphetamine Dependence. N -acetylcysteine (NAC) has been found to reduce the craving for Methamphetamine and other drugs, but its effect on Methamphetamine use and other clinically related endpoints are uncertain. The N-ICE trial is evaluating the safety and efficacy of NAC as a take-home pharmacotherapy for Methamphetamine Dependence.Methods/designThis is a two-arm parallel double-blind placebo-controlled three-site randomised trial (ratio 1:1) using permuted block randomisation, with variable block sizes. It is stratified by site, sex and whether the Methamphetamine is injected or not. Participants ( N = 180; 60 per site) need to be dependent on Methamphetamine, interested in reducing their Methamphetamine use and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2400 mg oral NAC or a matched placebo, delivered as a take-home medication for 12 weeks. Two 600 mg capsules are self-administered in the morning and two more in the evening. Adherence is being monitored using eCAP™ medication bottle lids, which record the date and time of each occasion the bottle is opened. The primary outcome is Methamphetamine use during the 12-week trial medication period, measured as (a) days of use, assessed using the timeline followback, and (b) Methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of Methamphetamine craving, severity of Methamphetamine Dependence, Methamphetamine withdrawal symptoms and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication.DiscussionThe N-ICE trial is the first clinical trial to assess whether NAC can reduce Methamphetamine use. This trial will improve our understanding of the potential utility of NAC in managing Methamphetamine Dependence and clinically related outcomes. If found to be effective, take-home NAC could be a potentially scalable and affordable pharmacotherapy option for treating Methamphetamine Dependence.Trial registrationAustralian and New Zealand Clinical Trials Registry, ACTRN12618000366257 . Registered on 29 May 2018.
-
a study protocol for the n ice trial a randomised double blind placebo controlled study of the safety and efficacy of n acetyl cysteine nac as a pharmacotherapy for Methamphetamine ice Dependence
Trials, 2019Co-Authors: Rebecca Mcketin, Alyna Turner, Brendan Quinn, Olivia M Dean, Dan I Lubman, Peter J KellyAbstract:There are currently no approved pharmacotherapies for managing Methamphetamine Dependence. N-acetylcysteine (NAC) has been found to reduce the craving for Methamphetamine and other drugs, but its effect on Methamphetamine use and other clinically related endpoints are uncertain. The N-ICE trial is evaluating the safety and efficacy of NAC as a take-home pharmacotherapy for Methamphetamine Dependence. This is a two-arm parallel double-blind placebo-controlled three-site randomised trial (ratio 1:1) using permuted block randomisation, with variable block sizes. It is stratified by site, sex and whether the Methamphetamine is injected or not. Participants (N = 180; 60 per site) need to be dependent on Methamphetamine, interested in reducing their Methamphetamine use and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2400 mg oral NAC or a matched placebo, delivered as a take-home medication for 12 weeks. Two 600 mg capsules are self-administered in the morning and two more in the evening. Adherence is being monitored using eCAP™ medication bottle lids, which record the date and time of each occasion the bottle is opened. The primary outcome is Methamphetamine use during the 12-week trial medication period, measured as (a) days of use, assessed using the timeline followback, and (b) Methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of Methamphetamine craving, severity of Methamphetamine Dependence, Methamphetamine withdrawal symptoms and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication. The N-ICE trial is the first clinical trial to assess whether NAC can reduce Methamphetamine use. This trial will improve our understanding of the potential utility of NAC in managing Methamphetamine Dependence and clinically related outcomes. If found to be effective, take-home NAC could be a potentially scalable and affordable pharmacotherapy option for treating Methamphetamine Dependence. Australian and New Zealand Clinical Trials Registry, ACTRN12618000366257 . Registered on 29 May 2018.
-
lima a study protocol for a randomised double blind placebo controlled trial of lisdexamfetamine for the treatment of Methamphetamine Dependence
BMJ Open, 2018Co-Authors: Nadine Ezard, Rebecca Mcketin, Jason M. White, Adrian Dunlop, Raimondo Bruno, Andrew Carr, Michelle Hall, Nghi Phung, Brendan CliffordAbstract:Introduction Methamphetamine Dependence is a growing public health concern. There is currently no pharmacotherapy approved for Methamphetamine Dependence. Lisdexamfetamine (LDX) dimesylate, used in the treatment of attention-deficit hyperactivity disorder and binge eating disorder, has potential as an agonist therapy for Methamphetamine Dependence, and possible benefits of reduced risk of aberrant use due to its novel formulation. Methods and analysis A double-blind randomised controlled trial will be used to evaluate the efficacy of LDX in reducing Methamphetamine use. The target sample is 180 participants with Methamphetamine Dependence of ≥2 years, using ≥14 days out of the previous 28, who have previously attempted but not responded to treatment for Methamphetamine use. Participants will be randomly assigned to receive either a 15-week intervention consisting of induction (1 week of 150 mg LDX or placebo), maintenance (12 weeks of 250 mg LDX or placebo) and reduction (1 week of 150 mg LDX or placebo and 1 week of 50 mg LDX or placebo). All participants will be given access to four sessions of cognitive–behavioural therapy as treatment as usual and receive a 4-week follow-up appointment. The primary outcomes are efficacy (change from baseline in days of Methamphetamine use by self-report for the last 28 days at week 13 and urinalyses confirmation of Methamphetamine use) and safety (treatment-related adverse events). Secondary outcomes are total number of days of self-report Methamphetamine use over the 12-week active treatment, longest period of abstinence during treatment period, percentage of achieving ≥21 days abstinence, craving, withdrawal, Dependence, retention, bloodborne virus transmission risk behaviour, criminal behaviour, as well measures of abuse liability, physical and mental health, other substance use, cognitive performance, psychosocial functioning, treatment retention and satisfaction. Additionally, the study will assess the cost-effectiveness of LDX relative to the placebo control. Ethics and dissemination The study has been approved by the Human Research Ethics Committee of St. Vincent’s Hospital, Sydney, Australia (HREC/16/SVH/222). Contact the corresponding author for the full trial protocol. Trial registration number ACTRN12617000657325; Pre-results.
-
A potential role for N-acetylcysteine in the management of Methamphetamine Dependence.
Drug and alcohol review, 2016Co-Authors: Rebecca Mcketin, Alyna Turner, Olivia M Dean, Peter J Kelly, Amanda Baker, Greg Carter, Michael BerkAbstract:Methamphetamine Dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of Methamphetamine Dependence. N-acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N-acetylcysteine also has antioxidant properties that protect against Methamphetamine-induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of Methamphetamine. This commentary overviews the actions of N-acetylcysteine and evidence for its efficacy in treating addiction with a particular focus on its potential utility for Methamphetamine Dependence. We conclude that the preliminary evidence indicates a need for full-scale trials to definitively establish whether N-acetylcysteine has a therapeutic benefit and the nature of this benefit, for managing Methamphetamine Dependence. [McKetin R, Dean O, Baker A. L, Carter G, Turner A, Kelly P. J, Berk M. A potential role for N-acetylcysteine in the management of Methamphetamine Dependence. Drug Alcohol Rev 2017;36:153-159].
-
typologies of positive psychotic symptoms in Methamphetamine Dependence
American Journal on Addictions, 2015Co-Authors: Chad A. Bousman, Rebecca Mcketin, Ian Everall, Hampton J. Atkinson, Erin E Morgan, Richard Burns, Steven Paul Woods, Igor GrantAbstract:Background and Objectives Understanding Methamphetamine associated psychotic (MAP) symptom typologies could aid in identifying individuals at risk of progressing to schizophrenia and guide early intervention.
Robert K. Heaton - One of the best experts on this subject based on the ideXlab platform.
-
sustained attention and vigilance deficits associated with hiv and a history of Methamphetamine Dependence
Drug and Alcohol Dependence, 2020Co-Authors: Nina Pocuca, Robert K. Heaton, Igor Grant, Jared W Young, David A Macqueen, Scott Letendre, Mark A Geyer, William Perry, Arpi MinassianAbstract:Abstract Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is Methamphetamine Dependence (METH). Such Dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, antiretroviral therapy initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; 50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the main and interactive (additive versus synergistic) effects of HIV and history of METH on the sustained attention and vigilance cognitive domain, while controlling for VLS. Methods Participants included 205 (median age = 44 years; 77% males; HIV-/METH- n = 67; HIV+/METH - n = 49; HIV-/METH+ n = 36; HIV+/METH+ n = 53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5-Choice continuous performance tests (CPTs). Results METH participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for Methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV- participants. There was no HIV x METH interaction on sustained attention and vigilance. Conclusions Recent Methamphetamine use among METH people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of antiretroviral therapy, and METH use interventions.
-
cerebrospinal fluid norepinephrine and neurocognition in hiv and Methamphetamine Dependence
Journal of Acquired Immune Deficiency Syndromes, 2020Co-Authors: Rowan Saloner, Mariana Cherner, Robert K. Heaton, Scott Letendre, Jennifer E Iudicello, Ronald J EllisAbstract:OBJECTIVE HIV disease and Methamphetamine (METH) Dependence share overlapping mechanisms of neurotoxicity that preferentially compromise monoamine-rich frontostriatal circuitry. However, norepinephrine (NE) function is poorly understood in HIV and METH Dependence. We evaluated associations between cerebrospinal fluid (CSF) NE and HIV, METH Dependence, and neurocognition. METHODS Participants included 125 adults, stratified by HIV serostatus (HIV+/HIV-) and recent METH Dependence (METH+/METH-), who underwent comprehensive neurocognitive testing and lumbar puncture. CSF NE was assayed using high-performance liquid chromatography. Multivariable regression modelled NE as a function of HIV, METH, and their interaction, adjusting for demographic and clinical factors. Pearson correlations examined relationships between NE and demographically-adjusted neurocognitive domain scores. RESULTS HIV significantly interacted with METH (P < 0.001) such that compared with HIV-/METH-, CSF NE was markedly elevated in the single risk-groups (HIV+/METH-: d = 0.96; HIV-/METH+: d = 0.79) and modestly elevated in the dual-risk group (HIV+/METH+: d = 0.48). This interaction remained significant after adjustment for lifetime depression, antidepressant use, and race/ethnicity. In the full sample, higher NE levels significantly correlated with worse global function (r = -0.19), learning (r = -0.23), and delayed recall (r = -0.18). Similar relationships between higher NE and worse neurocognition were detected in the METH- groups (ie, HIV-/METH- and HIV+/METH-) and in the virally-suppressed persons HIV+ subgroup, but not in the METH+ groups (ie, HIV-/METH+, HIV+/METH+). DISCUSSION HIV and METH independently, but not additively, relate to noradrenergic excess in the central nervous system, and perturbations to noradrenergic function may represent a pathophysiological mechanism of HIV-related neurocognitive dysfunction. Consistent with prior reports that noradrenergic excess compromises hippocampal and prefrontal function, higher NE related to worse neurocognition, even among successfully treated persons with HIV. Pharmacological and psychosocial interventions that stabilize NE function may improve neurocognition in persons with HIV.
-
sustained attention and vigilance deficits associated with hiv and a history of Methamphetamine Dependence
bioRxiv, 2020Co-Authors: Nina Pocuca, Robert K. Heaton, Igor Grant, Jared W Young, David A Macqueen, Scott Letendre, Mark A Geyer, William Perry, Arpi MinassianAbstract:Abstract Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is Methamphetamine Dependence (METH+). Such Dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, ART initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; ≤50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH+ on the sustained attention and vigilance cognitive domain, while controlling for VLS. Methods Participants included 205 (median age=44 years; 77% males; HIV-/METH- n=67; HIV+/METH - n=49; HIV-/METH+ n=36; HIV+/METH+ n=53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5- Choice continuous performance tests (CPTs). Results METH+ participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for Methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV-participants. There was no HIV x METH interaction on sustained attention and vigilance. Conclusions Recent Methamphetamine use among METH+ people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of ART, and METH use interventions.
-
everyday functional ability in hiv and Methamphetamine Dependence
Drug and Alcohol Dependence, 2017Co-Authors: Arpi Minassian, Robert K. Heaton, Scott Letendre, Brook L Henry, Jennifer E Iudicello, Erin E Morgan, William PerryAbstract:Abstract Background Methamphetamine (METH) use is a risk factor for the transmission of HIV. Each is associated with neurocognitive impairment and subsequent problems in everyday functioning, yet additive effects of HIV and METH are not consistently observed. This study used the UCSD Performance-Based Skills Assessment (UPSA-2) to assess whether METH use disorder and HIV together resulted in poorer functional outcome than either condition alone. Method Participants in the Translational Methamphetamine AIDS Research Center (TMARC) cohort were stratified based upon HIV infection and METH use disorder: HIV-/METH- (n = 49), HIV-/METH+ (n = 48), HIV+/METH- (n = 37), and HIV+/METH+ (n = 38). They were administered the UPSA-2 which measures abilities in six domains of everyday functioning. Main effects and interactions of HIV and METH were examined, as were relationships between UPSA-2 scores and disease characteristics. Results Significant HIV-by-METH interactions were observed for the UPSA-2 total score and Comprehension/Planning and Financial subscales such that METH was associated with lower scores in HIV- participants but not HIV+ participants. METH was associated with lower scores on the Communications subscale. All three risk groups had lower scores than HIV-/METH- participants. Recency and frequency of METH use were associated with lower scores. Lower Medication Management scores were related to lower nadir CD4 counts. Conclusions METH use disorder and HIV each impair functional performance, but there is no additive effect when the two conditions occur together. The neurocognitive sequelae of combined HIV infection and METH use are complex and warrant further study, as do the potential effects of compensatory strategies and other factors.
-
altered reward expectancy in individuals with recent Methamphetamine Dependence
Journal of Psychopharmacology, 2017Co-Authors: Amanda Bischoffgrethe, Gregory G. Brown, Martin P. Paulus, Colm G Connolly, Stephan J Jordan, Susan F Tapert, Robert K. HeatonAbstract:Background:Chronic Methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether Methamphetamine-dependent individuals show heightened reac...