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Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue, Makena Augenstein, Nayiri Alexander, Matthew Gartner

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6–6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to …

Utilizing Primary Care To Engage Patients On Opioids In A Psychological Intervention For Chronic Pain, Sikander Chohan, Lyuba Gavrilova Bs, Leah Hect, Kristi Autio, Erin Tobin, Brian K. Ahmedani, Lisa R. Miller-Matero

Medical Student Research Symposium

Introduction: Chronic pain is commonly encountered in primary care. It is often treated with opioids, which can cause overdose and death. Psychological interventions are an effective alternative, yet difficulty engaging patients with opioid prescriptions has led to their underutilization. Offering these interventions in primary care settings may alleviate this barrier.

Objective: Determine whether opioid prescriptions are related to patients engaging in a brief psychological intervention for chronic pain management in primary care.

Study Design: Secondary analysis of a pilot randomized clinical trial (RCT) of a 5-session psychological intervention for chronic pain. Patients with chronic pain (N= 220) were approached to …

The Feasibility And Utility Of Harnessing Digital Health To Understand Clinical Trajectories In Medication Treatment For Opioid Use Disorder: D-Tect Study Design And Methodological Considerations, Lisa A. Marsch, Ching-Hua Chen, Sara R. Adams, Asma Asyyed, Monique B. Does, Saeed Hassanpour, Emily Hichborn, Melanie Jackson-Morris, Nicholas C. Jacobson, Heather K. Jones, David Kotz, Chantal A. Lambert-Harris, Zhiguo Li, Bethany Mcleman, Varun Mishra, Catherine Stanger, Geetha Subramaniam, Weiyi Wu, Cynthia I. Campbell

Dartmouth Scholarship

Introduction: Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid …

Impact Of A Reduced Nicotine Standard On Young Adult Appeal For Menthol And Non-Menthol Cigarettes, Amy M. Cohn, Rachel Cassidy, Rachel Denlinger-Apte, Eric Donny, Andrea C. Villanti, Dorothy Hatsukami, Delaney Dunn, Riley Wyatt, Taylor Niznik, Tamar Cohen-Davidyan, Michael Smith, Sarah J. Ehlke

Psychology Faculty Publications

Introduction The Food and Drug Administration (FDA) announced its intention to reduce the nicotine content in cigarettes as a strategy to promote cessation and reduce smoking-related harm. A low nicotine product standard will apply to all cigarettes on the market, including menthol cigarettes. In December 2021, the FDA approved a modified risk tobacco product application for menthol and non-menthol flavoured very low nicotine cigarettes (VLNC) from the 22nd Century Group. Notably, experimentation with menthol cigarettes is linked to smoking progression, as well as greater nicotine dependence relative to non-menthol cigarette use. If menthol VLNCs are perceived as more appealing than …

Transcriptional Analysis Of The Response Of C. Elegans To Ethanol Exposure, Mark G. Sterken, Marijke H. Van Wijk, Elizabeth C. Quamme, Joost A. G. Riksen, Lucinda Carnell, Laura D. Mathies, Andrew G. Davies, Jan E. Kammenga, Jill C. Bettinger

Biology Faculty Scholarship

Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved …

Internet Pornography Addiction In The Treatment Of Heterosexual Dyadic Relationships: A Literature Review, Sarah Ogier-Bloomer

Antioch University Dissertations & Theses

The following dissertation provides a thorough literature review of internet pornography and internet pornography addiction for psychologists treating heterosexual couples in therapy and those training said clinicians. Factors that contribute to the development of compulsive sexual behavior are discussed, as well as how the addiction is maintained through reinforcing cycles. Factors including neuropsychological effects of neurotransmitters on the pleasure-reward system, insecure attachment, and childhood development provide insight into the manifestation of an addiction to pornography. Therefore, a thorough literature review on these aspects is necessary for current clinicians, as well as for those who are training clinicians. In addition, questionnaires …

A Markov Chain Approach For Forecasting Progression Of Opioid Addiction, Abhijit Gosavi, Susan L. Murray, N. Karagiannis

Engineering Management and Systems Engineering Faculty Research & Creative Works

The U.S. is currently facing an opioid crisis. Naltrexone is a common treatment for drug addiction; it reduces the desire to take opiates. However, addicts often stop treatment or continue to use opioids while in treatment. This results in increased fatalities and associated costs. A Markov-chain model is presented to analyze the progression of opioid addiction to assist the medical community in developing appropriate treatments. The model includes patients who continue opiate use while on naltrexone (blocked patients) and those who use opiates after missing naltrexone doses (unblocked patients). The other types of patients are abstinent (the best-case scenario) and …

Timely Linkage Of Individuals To Substance Use Disorder Treatment: Development, Implementation, And Evaluation Of Findhelpnowky.Org, Terry Lee Bunn, Dana Quesinberry, Tyler Jennings, Amber Kizewski, Heather Jackson, Sarah Mckee, Sarah Eustice

Kentucky Injury Prevention and Research Center Faculty Publications

Background: Substance use disorders (SUD) have steadily increased over the last two decades. Seeking SUD treatment involves searching SUD treatment facility types (inpatient, outpatient and intensive outpatient, residential and family residential, and detoxification facilities) that offer specialized SUD treatment depending on individual needs and preferences. Referrals to SUD treatment require innovative strategies that rapidly link individuals to SUD treatment when they are at the critical stage of readiness. The aim of this study was to develop, implement, and evaluate a user-friendly SUD treatment facility opening availability website called FindHelpNowKY.org. The objectives of the study were to 1) recruit SUD treatment …

A Randomized Placebo-Controlled Trial Of N-Acetylcysteine For Cannabis Use Disorder In Adults, Kevin M. Gray, Susan C. Sonne, Erin A. Mcclure, Udi E. Ghitza, Abigail G. Matthews, Aimee L. Mcrae-Clark, Kathleen M. Carroll, Jennifer S. Potter, Katharina Wiest, Larissa J. Mooney, Albert Hasson, Sharon L. Walsh, Michelle R. Lofwall, Shanna Babalonis, Robert W. Lindblad, Steven Sparenborg, Aimee Wahle, Jacqueline S. King, Nathaniel L. Baker, Rachel L. Tomko, Louise F. Haynes, Ryan G. Vandrey, Frances R. Levin

Behavioral Science Faculty Publications

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults.

Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All …

Neurophysiological Capacity In A Working Memory Task Differentiates Dependent From Nondependent Heavy Drinkers And Controls, Michael J. Wesley, Joshua A. Lile, Mark T. Fillmore, Linda J. Porrino

Behavioral Science Faculty Publications

Background—Determining the brain-behavior profiles that differentiate heavy drinkers who are and are not alcohol dependent will inform treatment efforts. Working memory is linked to substance use disorders and can serve as a representation of the demand placed on the neurophysiology associated with cognitive control.

Methods—Behavior and brain activity (via fMRI) were recorded during an N-Back working memory task in controls (CTRL), nondependent heavy drinkers (A-ND) and dependent heavy drinkers (A-D). Typical and novel step-wise analyses examined profiles of working memory load and increasing task demand, respectively.

Results—Performance was significantly decreased in A-D during high working memory load …

A Qualitative Analysis Of The Health Informatics Role In Addressing The Public Health Crisis Of Addiction And Overall Effectiveness Of Treatment, Daniel Del Toro

Applied Research Projects

In recent years, the implementation of Health Information Management (HIM) data systems has had significant positive impacts in nearly all aspects of both health and healthcare delivery. However, during this time, there has also been a dramatic increase in the demand for addiction and mental health treatment. The rising number of individuals requiring mental health treatment for addiction has resulted in its declaration as an urgent public health epidemic by the Department of Health and Human Services. The all-encompassing effects of addiction are prevalent in all areas of society, seen in the form of across-the-board rising healthcare costs, addiction related …

Exposure To Kynurenic Acid During Adolescence Increases Sign-Tracking And Impairs Long-Term Potentiation In Adulthood, Nicole E. Deangeli, Travis P. Todd, Stephen E. Chang, Hermes H. Yeh, Pamela W. Yeh, David J. Bucci

Dartmouth Scholarship

Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and …

Impulsivity, Impulsive And Reflective Processes And The Development Of Alcohol Use And Misuse In Adolescents And Young Adults, Reinout W. Wiers, Susan L. Ames, Wilhelm Hofmann, Marvin Krank, Alan W. Stacy

CGU Faculty Publications and Research

This paper contrasts dual-process and personality approaches in the prediction of addictive behaviors and related risk behaviors. In dual-process models, behavior is described as the joint outcome of qualitatively different “impulsive” (or associative) and “reflective” processes. There are important individual differences regarding both types of processes, and the relative strength of both in a specific situation is influenced by prior behavior and state variables (e.g., fatigue, alcohol use). From this perspective, a specific behavior (e.g., alcohol misuse) can be predicted by the combined indices of the behavior-related impulsive processes (e.g., associations with alcohol), and reflective processes, including the ability to …