REINFORCING, SUBJECTIVE, AND COGNITIVE EFFECTS OF METHAMPHETAMINE DURING D-AMPHETAMINE MAINTENANCE

Translational research suggests that agonist replacement may be a viable treatment approach for managing methamphetamine dependence. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using participants. A cognitive battery was used to determine the performance effects of methamphetamine alone and during d-amphetamine maintenance. During each maintenance condition, participants first sampled a dose of intranasal methamphetamine then had the opportunity to respond on a progressive ratio task to earn portions of the sampled dose. Subject-rated drug-effect and physiological measures were completed prior to and after sampling methamphetamine. Methamphetamine was self-administered as function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects, some of which were attenuated by d-amphetamine maintenance. Methamphetamine was well tolerated during d-amphetamine maintenance and no adverse events occurred. The self-administration results are concordant with those of clinical trials that show d-amphetamine did not reduce methamphetamine use. Generally, there was no difference in cognitive performance after methamphetamine administration during both placebo and d-amphetamine maintenance. Overall d-amphetamine does not appear to be a viable treatment for preventing methamphetamine relapse, but translational literature suggests that other agonist medications or the combination of pharmacotherapy and behavioral therapies may be effective

THE INFLUENCE OF COCAINE-RELATED IMAGES ON INHIBITORY CONTROL IN COCAINE USERS

Cocaine users display impaired inhibitory control. The influence of cocaine-related stimuli on inhibitory control has not been assessed. The Attentional Bias-Behavioral Activation (ABBA) task uses cocaine and neutral images as cues to determine if drug-related images impair inhibitory control in cocaine users. This dissertation was designed to assess the influence of cocaine images on inhibitory control in cocaine users through the conduct of studies designed to address four aims. The first aim was to demonstrate that cocaine users display impaired inhibitory control following cocaine images compared to neutral images on the ABBA task. This was accomplished through the conduct of two experiments. The first experiment piloted the ABBA task and cocaine users completed the cocaine go (n = 15) or neutral go condition (n = 15) of the task. The second experiment consisted of two studies designed to develop a within-subjects methodology for using the ABBA task. In the first study, cocaine users completed either the cocaine go (n = 20) or neutral go (n = 20) condition of the ABBA task and all participants also completed the Cued Go/No-Go task, with geometric shapes as cues. In the second study, cocaine users (n = 18) completed the cocaine go condition of the ABBA task and a modified version of the ABBA task with all neutral images as cues to further refine a possible within-subjects methodology. The second aim was to demonstrate that inhibitory failures occur most often when cues are presented for short compared to longer durations of time. Data collected during other protocols (n = 91) were combined to investigate the influence of stimulus onset asynchrony (SOA; i.e., the amount of time a cue is presented before a target indicated a response should be executed or withheld) on inhibitory control following cocaine-related and neutral cues on the ABBA task. The third aim was to demonstrate impaired inhibitory control following cocaine images on the ABBA task is specific to cocaine users. Cocaine users (data collected in the second experiment of the first aim) and non-using control participants (n = 16) completed the cocaine go and all neutral conditions of the ABBA task and the Cued Go/No-Go task. The fourth aim was to demonstrate the feasibility and acceptability of inhibitory control training to cocaine-related stimuli with cocaine users. A small pilot clinical trial was conducted and cocaine users were randomly assigned to complete inhibitory control training to cocaine images or geometric shapes. Cocaine images impaired inhibitory control on the ABBA task, as demonstrated by an increased proportion of inhibitory failures in the cocaine go condition compared to the neutral go condition in Experiments 1, 2, and 4. The proportion of inhibitory failures following cocaine images in Experiment 4 was increased at short (i.e., 100, 200) compared to long SOAs. Cocaine images also impaired inhibitory control compared to the Cued Go/No-Go Task in Experiment 2, however there were no differences in the proportion of inhibitory failures between the cocaine go and all neutral conditions of the ABBA task. There were no differences between cocaine users and controls in Experiment 3 for the proportion of inhibitory failures on the ABBA or Cued Go/No-Go tasks, but controls responded faster indicating a speed/accuracy trade off occurred in the control group. Inhibitory control training as an approach to improve treatment outcomes is feasible, as indicated by attendance and accuracy on the training task, and participants rated the overall procedure as satisfactory in Experiment 5. A better understanding of inhibitory control in the presence of cocaine related cues could be crucial to better understand how drug cues contribute to the risk for relapse and the continued use of drugs because both occur in the presence of drug cues

A Latent Profile Analysis of Rural Women Who Use Drugs and Commit Crimes

The majority of rural Appalachian women in jail meet criteria for a drug use disorder and need treatment. Using a latent profile analysis of a random sample of rural women in Appalachian jails (N=400) the current study established groups of women based on criminal history, drug use in the commission of crimes, and role of the partner’s drug use in the commission of crimes. Analysis found five distinct profiles of rural women based on involvement of criminal activities as a function of drug use severity. Results suggest that among criminally involved rural women, severity of drug use is a critical factor in the criminal career. Findings can be used to better inform treatment approaches and tailor treatment to meet the needs of this vulnerable population

Rural Re-entry and Opioid Use: Identifying Health-Related Predictors of Relapse Among Formerly Incarcerated Women in Appalachia

Introduction: Despite improved knowledge of the health care needs of formerly incarcerated women, there exists a gap regarding the relationship between health, health care access, and relapse among rural women returning to the community during the opioid epidemic. Purpose: With an emphasis on health care access, this study examined health-related factors associated with opioid relapse among women reentering the community in rural Appalachia. Methods: As part of a larger study, 400 rural women reporting a history of substance use were recruited from three Appalachian jails in Kentucky. Analyses focused on participants reporting a history of illicit opioid use prior to incarceration, who had also completed follow-up interviews at 6- and 12-months post-release from jail. Results: Fifty-five percent of participants reported relapse to opioids during the 12-month follow-up period. Compared to those who did not use opioids during this time, women who relapsed reported poorer mental and physical health, as well as encountered more barriers to needed health services. They were also more likely to report a usual source of care. Multivariate regression analyses reveal that, even when controlling for other known correlates of opioid use and relapse to any non-opioid drug during the follow-up period, the number of barriers to health service utilization was a significant predictor of opioid relapse. Implications: Stakeholders should address the complex reentry needs of women who use opioids in rural Appalachia. This includes examining innovative approaches to reduce extensive barriers to quality health care utilization, such as implementing telehealth for opioid use treatment

A Pilot Investigation of Acute Inhibitory Control Training in Cocaine Users

Background—Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. Methods—Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. Results—Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. Conclusions—Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities

Adaptation of a Standard Extended-Release Naltrexone (XR-NTX) Protocol for Rural Re-Entering Offenders with OUD

BACKGROUND: Despite a growing body of empirical support for the effectiveness of extended-release naltrexone (XR-NTX) to reduce opioid relapse among people with opioid use disorder (OUD) transitioning from a correctional facility to the community, continuity of care following release remains challenging. This paper describes a research-based adaptation of a state\u27s standard of care XR-NTX protocol using the ADAPT-ITT framework for delivery in a non-traditional, non-treatment, community criminal justice setting (P&P office), as well as the expansion of services by a local Federally Qualified Health Center (FQHC) provider who would, for the first time, be going to the jail and P&P office to provide XR-NTX and related treatment. METHOD: The present study focuses on the first seven phases (Assessment through Training) of the ADAPT-ITT framework in the adaptation of the Department of Corrections (DOC) protocol in preparation for a pilot trial for induction in a rural jail and during the transition to a rural community. Expert clinical review and focus groups with key stakeholders in criminal justice supervision and the local providers in the FQHC informed the needed adaptations to the existing XR-NTX protocol for initiation at the jail and ongoing administrations in the community. RESULTS: Findings from stakeholder focus groups, study team review, topical expert review, and a theater test suggested that there were critical adaptations needed in both content and context at the patient and clinic level. CONCLUSION: Health and justice officials should consider the need to tailor and adapt evidence-based approaches for real-world locations that high-risk, justice-involved individuals visit in order to reduce barriers and increase access to critically needed treatment for OUD

Interaction between Amyloid Beta Peptide and an Aggregation Blocker Peptide Mimicking Islet Amyloid Polypeptide

Assembly of amyloid-beta peptide (Aβ) into cytotoxic oligomeric and fibrillar aggregates is believed to be a major pathologic event in Alzheimer's disease (AD) and interfering with Aβ aggregation is an important strategy in the development of novel therapeutic approaches. Prior studies have shown that the double N-methylated analogue of islet amyloid polypeptide (IAPP) IAPP-GI, which is a conformationally constrained IAPP analogue mimicking a non-amyloidogenic IAPP conformation, is capable of blocking cytotoxic self-assembly of Aβ. Here we investigate the interaction of IAPP-GI with Aβ40 and Aβ42 using NMR spectroscopy. The most pronounced NMR chemical shift changes were observed for residues 13–20, while residues 7–9, 15–16 as well as the C-terminal half of Aβ - that is both regions of the Aβ sequence that are converted into β-strands in amyloid fibrils - were less accessible to solvent in the presence of IAPP-GI. At the same time, interaction of IAPP-GI with Aβ resulted in a concentration-dependent co-aggregation of Aβ and IAPP-GI that was enhanced for the more aggregation prone Aβ42 peptide. On the basis of the reduced toxicity of the Aβ peptide in the presence of IAPP-GI, our data are consistent with the suggestion that IAPP-GI redirects Aβ into nontoxic “off-pathway” aggregates

Feasibility of using Facebook for HIV prevention: Implications for translational research among justice-involved women who use drugs in rural Appalachia

BackgroundJustice-involved women from rural Appalachia face significant barriers to the utilization of evidence-based HIV prevention interventions in spite of high rates of injection drug use and risky sexual practices. Adapting evidence-based practices to incorporate the cultural uniqueness of the target population is needed in order to advance translational and clinical science in this area. This study provides a descriptive overview of indicators of feasibility and acceptability of an adapted version of the National Institute on Drug Abuse Standard HIV prevention intervention for delivery using Facebook through a small randomized controlled pilot study with rural Appalachian women.MethodStudy methods include the random selection of rural Appalachian women from two local jails, screening for study eligibility, baseline data collection, random assignment to study interventions, and follow-up in the community three months post-release.ResultsResults indicate that the feasibility of the approach was supported through study enrollment of the target population who reported regular Facebook use and HIV risk behaviors including drug use and sex. Acceptability of the intervention was demonstrated through enrollment in the study intervention, engagement in the intervention through Facebook, and indicators of HIV/HCV knowledge.ConclusionsStudy findings contribute to the critical and unmet need to advance translational science on the delivery of evidence-based prevention interventions in real-world rural Appalachian settings to understudied, vulnerable individuals who are often overlooked in targeted prevention efforts

An Exploratory Examination of Social Media Use and Risky Sexual Practices: A Profile of Women in Rural Appalachia Who Use Drugs

HIV/HCV risk behavior among women who use drugs is often exacerbated within high risk networks. The use of social media platforms such as Facebook to identify sex partners within these high-risk networks has not been examined among rural Appalachian women who use drugs. This paper provides an exploratory examination of Facebook use to identify sex partners among rural Appalachian women who use drugs, as well as associated risky sexual practices. Rural Appalachian women were randomly selected from two rural jails, consented, screened for eligibility (including drug use), and interviewed prior to jail release. Findings indicated that using Facebook to meet sex partners was associated with exchanging sex for drugs or money and having a male casual partner during the same time frame. These study findings suggest that the use of social media for high-risk sexual practices may provide a valuable platform for intervention delivery, particularly in resource-deprived areas where formal prevention and treatment services are limited