Browsing by Subject "Opioid"

Now showing 1 - 10 of 25
  • Thumbnail Image
    Item
    Community Conditions Favorable for Substance Use
    (The Center for Health Policy, 2018-04-01) Jacinto, Corey; Greene, Marion S.
    The probability of whether an individual engages in substance use is associated with several risk and protective factors. Effective prevention requires understanding these factors. The social-ecological model considers the complex interactions between individual, relationship, community, and societal factors. This can help us understand substance use in a public health context and design strategies to address the problem across multiple levels.
  • Thumbnail Image
    Item
    Contribution of Behavioral Health Factors to Non-AIDS-Related Comorbidities: an Updated Review
    (SpringerLink, 2020-08) Chichetto, Natalie E.; Polanka, Brittanny M.; So-Armah, Kaku A.; Sung, Minhee; Stewart, Jesse C.; Koethe, John R.; Edelman, E. Jennifer; Tindle, Hilary A.; Freiberg, Matthew S.; Psychology, School of Science
    Purpose of review: We summarize recent literature on the contribution of substance use and depression to non-AIDS-related comorbidities. Discussion of recent randomized clinical trials and implementation research to curtail risk attributed to each behavioral health issue is provided. Recent findings: Smoking, unhealthy alcohol use, opioid use, and depression are common among PWH and individually contribute to increased risk for non-AIDS-related comorbidities. The concurrence of these conditions is notable, yet understudied, and provides opportunity for linked-screening and potential treatment of more than one behavioral health factor. Current results from randomized clinical trials are inconsistent. Investigating interventions to reduce the impact of these behavioral health conditions with a focus on implementation into clinical care is important. Non-AIDS-defining cancers, cardiovascular disease, liver disease, and diabetes are leading causes of morbidity in people with HIV. Behavioral health factors including substance use and mental health issues, often co-occurring, likely contribute to the excess risk of non-AIDS-related comorbidities.
  • Thumbnail Image
    Item
    The Enduring Consequences of Prenatal Opioid Exposure
    (2022-02) Grecco, Gregory Giovanni; Sheets, Patrick; Atwood, Brady; Yamamoto, Bryan; McKinzie, David; Yoder, Karmen
    The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure; however, the long-term effects of opioid exposure on offspring behavior and neurodevelopment remain relatively unknown. I developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. PME produced substantial impairments in offspring growth, sensorimotor milestone acquisition, and activity in an open field. Furthermore, these behavioral alterations were associated with significant disruptions in the primary motor cortex (M1). Notably, layer 5 pyramidal neurons of the M1 displayed significantly increased voltage sag which is primarily mediated by HCN1 channels. Interestingly, the α2-adrenergic receptor, a known modulator of HCN1 channels, displayed significantly increased expression in the M1 of PME animals. The locomotor activity in an open field was significantly reduced following in vivo pharmacological activation of the α2-adrenergic receptor with clonidine in PME offspring suggesting this may be therapeutic target for the hyperactivity associated with prenatal exposure to opioids. Previous work has also described an association between prenatal opioid exposure and alterations in opioid reward-related behavior; however, the effect of PME on alcohol reward remains undetermined. Given the widespread accessibility and usage, alcohol represents the most likely addictive substance the growing population of opioid exposed neonates will encounter as they age. I discovered that PME disrupts conditioned preference for alcohol, enhances the locomotor stimulating effects of alcohol, and increases alcohol consumption in a sex-dependent manner. This alcohol-reward phenotype in PME offspring was associated with altered excitatory neurotransmission and disrupted cannabinoid-mediated long-term depression (CB-LTD) in the dorsolateral striatum, an important substrate involved in compulsive drug use. Further work is required to determine the specific inputs at which CB-LTD is disrupted and if restoring this form of plasticity in PME animals prevents the enhanced alcohol addiction phenotype.
  • Thumbnail Image
    Item
    Evaluation of Individualized Pain Plans for Children With Sickle Cell Disease Admitted for Vaso-occlusive Crisis at Riley Hospital for Children
    (Allen Press, 2022) Arends, Alexandria M.; Perez, Anne; Wilder, Christina; Jacob, Seethal A.; Pediatrics, School of Medicine
    Objective: Vaso-occlusive crisis (VOC) is the most common problem reported by patients with sickle cell disease (SCD). The objective of this study was to evaluate the impact of individualized pain plans in pediatric patients with SCD admitted for VOC. Methods: This was a pre- and post-study of patients with SCD admitted to Riley Hospital for Children for VOC from July 1, 2019, through July 1, 2020. The primary outcome was length of inpatient stay for VOC. Secondary outcomes included final pain score, days on scheduled opioids, days on breakthrough opioids, and average morphine milligram equivalents (MME) used per day. Results: Nine patients were included. The mean age was 16 years (range, 10-20 years). Key clinical findings were decreases in median [IQR] for final pain scores (7 [4.5-9] vs 6 [2.5-8], p = 0.396) and number of days of breakthrough opioid use (5 [3-8] vs 4 [2.5-5.5], p = 0.233). Following implementation of an individualized pain plan, there was an increase in median average MME per day (65.94 [53.1-97.7] vs 82.85 [41-114.3], p = 0.844). Median length of stay and days on scheduled opioids remained the same. Conclusions: This study demonstrated that use of individualized pain plans in a small population of patients with SCD might result in decreased pain scores and decreased days on breakthrough opioids.
  • Thumbnail Image
    Item
    HCN1 channels mediate mu opioid receptor long-term depression at insular cortex inputs to the dorsal striatum
    (Wiley, 2022) Munoz, Braulio; Fritz, Brandon M.; Yin, Fuqin; Atwood, Brady K.; Pharmacology and Toxicology, School of Medicine
    Mu opioid receptors (MORs) are expressed in the dorsal striatum, a brain region that mediates goal-directed (via the dorsomedial striatum) and habitual (via the dorsolateral striatum, DLS) behaviours. Our previous work indicates that glutamate transmission is depressed when MORs are activated in the dorsal striatum, inducing MOR-mediated long-term synaptic depression (MOR-LTD) or short-term depression (MOR-STD), depending on the input. In the DLS, MOR-LTD is produced by MORs on anterior insular cortex (AIC) inputs and MOR-STD occurs at thalamic inputs, suggesting input-specific MOR plasticity mechanisms. Here, we evaluated the mechanisms of induction of MOR-LTD and MOR-STD in the DLS using pharmacology and optogenetics combined with patch-clamp electrophysiology. We found that cAMP/PKA signalling and protein synthesis are necessary for MOR-LTD expression, similar to previous studies of cannabinoid-mediated LTD in DLS. MOR-STD does not utilize these same mechanisms. We also demonstrated that cannabinoid-LTD occurs at AIC inputs to DLS. However, while cannabinoid-LTD requires mTOR signalling in DLS, MOR-LTD does not. We characterized the role of presynaptic HCN1 channels in MOR-LTD induction as HCN1 channels expressed in AIC are necessary for MOR-LTD expression in the DLS. These results suggest a mechanism in which MOR activation requires HCN1 to induce MOR-LTD, suggesting a new target for pharmacological modulation of synaptic plasticity, providing new opportunities to develop novel drugs to treat alcohol and opioid use disorders. KEY POINTS: Mu opioid receptor-mediated long-term depression at anterior insular cortex inputs to dorsolateral striatum involves presynaptic cAMP/PKA signalling and protein translation, similar to known mechanisms of cannabinoid long-term depression. Dorsal striatal cannabinoid long-term depression also occurs at anterior insular cortex inputs to the dorsolateral striatum. Dorsal striatal cannabinoid long-term depression requires mTOR signalling, similar to hippocampal cannabinoid long-term depression, but dorsal striatal mu opioid long-term depression does not require mTOR signalling. Mu opioid long-term depression requires presynaptic HCN1 channels at anterior insular cortex inputs to dorsolateral striatum.
  • Thumbnail Image
    Item
    The Impact of Substance Use on the Developing Brain
    (The Center for Health Policy, 2017-07-01) Kooreman, Harold E.
    Most peoples’ first exposure to alcohol, tobacco, and other drugs typically occurs during adolescence, a time when the brain changes rather dramatically. The maturation process of the adolescent brain is reflected in a greater propensity to take part in risky activities such as unprotected sex, reckless driving, and substance use. Alcohol, nicotine, and marijuana, the most commonly used substances by teens, have all been tied to disruptions in normal brain development. These structural changes are associated with higher rates of cognitive impairments and academic difficulties, higher rates of future substance use and substance use disorders, and higher rates of mood and psychotic disorders.
  • Thumbnail Image
    Item
    Lay responder naloxone access and Good Samaritan law compliance: postcard survey results from 20 Indiana counties
    (BioMed Central, 2018-04-06) Watson, Dennis P.; Ray, Bradley; Robison, Lisa; Huynh, Philip; Sightes, Emily; Walker, La Shea; Brucker, Krista; Duwve, Joan; Social and Behavioral Sciences, School of Public Health
    BACKGROUND: To reduce fatal drug overdoses, two approaches many states have followed is to pass laws expanding naloxone access and Good Samaritan protections for lay persons with high likelihood to respond to an opioid overdose. Most prior research has examined attitudes and knowledge among lay responders in large metropolitan areas who actively use illicit substances. The present study addresses current gaps in knowledge related to this issue through an analysis of data collected from a broader group of lay responders who received naloxone kits from 20 local health departments across Indiana. METHODS: Postcard surveys were included inside naloxone kits distributed in 20 Indiana counties, for which 217 returned cards indicated the person completing it was a lay responder. The survey captured demographic information and experiences with overdose, including the use of 911 and knowledge about Good Samaritan protections. RESULTS: Few respondents had administered naloxone before, but approximately one third had witnessed a prior overdose and the majority knew someone who had died from one. Those who knew someone who had overdosed were more likely to have obtained naloxone for someone other than themselves. Also, persons with knowledge of Good Samaritan protections or who had previously used naloxone were significantly more likely to have indicated calling 911 at the scene of a previously witnessed overdose. Primary reasons for not calling 911 included fear of the police and the person who overdosed waking up on their own. CONCLUSIONS: Knowing someone who has had a fatal or non-fatal overdose appears to be a strong motivating factor for obtaining naloxone. Clarifying and strengthening Good Samaritan protections, educating lay persons about these protections, and working to improve police interactions with the public when they are called to an overdose scene are likely to improve implementation and outcomes of naloxone distribution and opioid-related Good Samaritan laws.
  • Thumbnail Image
    Item
    Liver Injury Associated with Kratom, A Popular Opioid-Like Product: Experience from the U.S. Drug Induced liver Injury Network
    (Elsevier, 2021) Ahmad, Jawad; Odin, Joseph A.; Hayashi, Paul H.; Fontana, Robert J.; Conjeevaram, Hari; Avula, Bharathi; Khan, Ikhlas A.; Barnhart, Huiman; Vuppalanchi, Raj; Navarro, Victor J.; Drug-Induced Liver Injury Network; Medicine, School of Medicine
    Background: Kratom is a botanical product used as an opium substitute with abuse potential. Methods: Assessment of suspected cases of kratom-induced liver injury in a prospective US cohort. Results: Eleven cases of liver injury attributed to kratom were identified with a recent increase. The majority were male with median age 40 years. All were symptomatic and developed jaundice with a median latency of 14 days. The liver injury pattern was variable, most required hospitalization and all eventually recovered. Biochemical analysis revealed active kratom ingredients. Conclusion: Kratom can cause severe liver injury with jaundice.
  • Thumbnail Image
    Item
    Opioid Overdoses in Indiana: A Closer Look at Opioid Type
    (The Center for Health Policy, 2018-06-01) Kooreman, Harold E.
    The misuse of prescription and illicit opioids remains at epidemic proportions, costing the United States billions of dollars annually. Overdose deaths in both the U.S. and Indiana have seen a dramatic increase over the past ten years. Until recently, prescription opioids were responsible for the greatest number of overdose deaths, but now have been surpassed by fatalities involving heroin and illicitly manufactured narcotics, primarily fentanyl.
  • Thumbnail Image
    Item
    Opioid Overdoses in Indiana: A Closer Look at Opioid Type
    (The Center for Health Policy, 2018-06-01) Kooreman, Harold
    The misuse of prescription and illicit opioids remains at epidemic proportions, costing the United States billions of dollars annually. Overdose deaths in both the U.S. and Indiana have seen a dramatic increase over the past ten years. Until recently, prescription opioids were responsible for the greatest number of overdose deaths, but now have been surpassed by fatalities involving heroin and illicitly manufactured narcotics, primarily fentanyl.