Systematic review of Pharmacogenomics Knowledgebase evidence for pharmacogenomic links to the dopamine reward pathway for heroin dependence

2021 ◽  
Vol 22 (13) ◽  
pp. 849-857
Author(s):  
Maggie L McCorkle ◽  
David F Kisor ◽  
Caroline E Freiermuth ◽  
Jon E Sprague
Keyword(s):  
Opioid Use Disorder ◽  
Heroin Dependence ◽  
The Body ◽  
Specific Gene ◽  
Gene Variants ◽  
Opioid Use ◽  
Level Of Evidence ◽  
Increased Risk ◽  
Reward Pathway ◽  
Reward Pathways

Genetics play an important role in opioid use disorder (OUD); however, few specific gene variants have been identified. Therefore, there is a need to further understand the pharmacogenomics influences on the pharmacodynamics of opioids. The Pharmacogenomics Knowledgebase (PharmGKB), a database that links genetic variation and drug interaction in the body, was queried to identify polymorphisms associated with heroin dependence in the context of opioid related disorders/OUD. Eight genes with 22 variants were identified as linked to increased risk of heroin dependence, with three genes and variants linked to decreased risk, although the level of evidence was moderate to low. Therefore, continued exploration of biomarker influences on OUD, reward pathways and other contributing circuitries is necessary to understand the true impact of genetics on OUD before integration into clinical guidelines.

scholarly journals Buprenorphine exposure alters the development and migration of interneurons in the cortex

2020 ◽  
Author(s):  
Vanesa Nieto-Estévez ◽  
Jennifer J. Donegan ◽  
Courtney McMahon ◽  
Hannah B. Elam ◽  
Teresa A. Chavera ◽  
...  
Keyword(s):  
Human Brain ◽  
Fetal Brain ◽  
Opioid Use Disorder ◽  
Prescription Opioid ◽  
Opioid Use ◽  
Child Bearing ◽  
Increased Risk ◽  
Adverse Neonatal Outcomes ◽  
And Migration ◽  
Long Acting

ABSTRACTThe misuse of opioids has reached epidemic proportions over the last decade, with over 2.1 million people in the U.S. suffering from substance use disorders related to prescription opioid pain relievers. This increase in opioid misuse affects all demographics of society, including women of child-bearing age, which has led to a rise in opioid use during pregnancy. Opioid use during pregnancy has been associated with increased risk of obstetric complications and adverse neonatal outcomes, including neonatal abstinence syndrome. Currently, opioid use disorder in pregnant women is treated with long-acting opioid agonists, including buprenorphine. Although buprenorphine reduces illicit opioid use during pregnancy and improves infant outcomes at birth, few long-term studies of the neurodevelopmental consequences have been conducted. The goal of the current experiments was to examine the effects of buprenorphine on the development of the cortex using fetal brain tissue, 3D brain cultures, and rodent models. First, we demonstrated that we can grow cortical and subpallial spheroids, which model the cellular diversity, connectivity, and activity of the developing human brain. Next, we show that cells in the developing human cortex express the nociceptin opioid (NOP) receptor and that buprenorphine can signal through this receptor in cortical spheroids. Using subpallial spheroids to grow inhibitory interneurons, we show that buprenorphine can alter interneuron development and migration into the cortex. Finally, using a rodent model of prenatal buprenorphine exposure, we demonstrate that alterations in interneuron distribution can persist into adulthood. Together, these results suggest that more research is needed into the long-lasting consequences of buprenorphine exposure on the developing human brain.

Maternal and neonatal characteristics of a Canadian urban cohort receiving treatment for opioid use disorder during pregnancy

2018 ◽  
Vol 10 (1) ◽  
pp. 132-137 ◽  
Author(s):  
C. Miller ◽  
D. Grynspan ◽  
L. Gaudet ◽  
E. Ferretti ◽  
S. Lawrence ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Retrospective Chart Review ◽  
Opioid Use Disorder ◽  
Prescription Opioid ◽  
Opioid Use ◽  
Maternal Characteristics ◽  
Ottawa Hospital ◽  
Increased Risk ◽  
Opioid Replacement Therapy ◽  
In Pregnancy

AbstractThe epidemic of prescription and non-prescription opioid misuse is of particular importance in pregnancy. The Society of Obstetricians and Gynaecologists of Canada currently recommends opioid replacement therapy with methadone or buprenorphine for opioid-dependent women during pregnancy. This vulnerable segment of the population has been shown to be at increased risk of blood-borne infectious diseases, nutritional insecurity and stress. The objective of this study was to describe an urban cohort of pregnant women on opioid replacement therapy and to evaluate potential effects on the fetus. A retrospective chart review of all women on opioid replacement therapy and their infants who delivered at The Ottawa Hospital General and Civic campuses between January 1, 2013 and March 24, 2017 was conducted. Data were collected on maternal characteristics, pregnancy outcomes, neonatal outcomes and corresponding placental pathology. Maternal comorbidities identified included high rates of infection, tobacco use and illicit substance use, as well as increased rates of placental abruption compared with national averages. Compared with national baseline averages, the mean neonatal birth weight was low, and the incidence of small for gestational age infants and congenital anomalies was high. The incidence of NAS was comparable with estimates from other studies of similar cohorts. Findings support existing literature that calls for a comprehensive interdisciplinary risk reduction approach including dietary, social, domestic, psychological and other supports to care for opioid-dependent women in pregnancy.

scholarly journals 0259 Shiftworkers are at Increased Risk of Developing Chronic Pain and Opioid Use Disorders: A Study of 116,000 UK Biobank Participants Over a Decade

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A98-A99
Author(s):  
L Gao ◽  
P Li ◽  
L Cui ◽  
Y Luo ◽  
C Vetter ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Bone Fractures ◽  
Inflammatory Diseases ◽  
Opioid Use Disorder ◽  
Uk Biobank ◽  
Opioid Use ◽  
Logistic Regression Models ◽  
Diagnostic Coding ◽  
Increased Risk ◽  
Opioid Use Disorders

Abstract Introduction In the current epidemic of opioid-related deaths, and widespread use of opioids to treat chronic pain, there is a pressing need to understand the underlying risk factors that contribute to such devastating conditions. Shiftwork has been associated with adverse health outcomes. We tested whether shiftwork during middle age is linked to the development of chronic pain and opioid misuse. Methods We studied 116,474 participants in active employment between 2006–2010 (mean age 57±8; range 37–71) from the UK Biobank, who have been followed for up to 10 years until 2017. We included participants who were free from all forms of self-reported pain, and were not taking opioid medications at baseline. Chronic pain and opioid use disorder diagnoses were determined using hospitalization records and diagnostic coding from ICD-10. Multivariate logistic regression models were performed to examine the associations of shiftwork status (yes/no) and nightshift frequency (none/occasional/permanent) and with incident chronic pain and/or opioid use disorder during follow-up. Models were adjusted for demographics, education, Townsend deprivation index, major confounders (BMI, diabetes, bone fractures/injuries, operations, peripheral vascular disease, joint/inflammatory diseases, cancer, standing/manual labor at work) and covariates (smoking, alcohol, high cholesterol, depression/anxiety, and cardiovascular diseases). Results In total, 190 (1.6/1,000) developed chronic pain or opioid use disorders. Shiftworkers (n=17,673) saw a 1.5-fold increased risk (OR 1.56, 95% CI: 1.08–2.24, p=0.01) relative to day workers. Within shiftworkers, those who reported occasional nightshift work (n=3,966) were most vulnerable (OR 1.57, 95% CI: 1.06–2.34, p=0.02). Results remained similar after adjusting for baseline sleep duration, chronotype and insomnia. Conclusion Shiftwork, and in particular rotating nightshift work is associated with increased risk for developing chronic pain and opioid use disorders. Replication is required to confirm the findings and to examine underlying mechanisms. Support This work was supported by NIH grants T32GM007592, RF1AG064312, and RF1AG059867.

scholarly journals 213. A Comparison of Medication Assisted Therapy Treatment Strategies for Opioid Use Disorder in Persons who Inject Drugs and are Hospitalized with Serious Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S126-S126
Author(s):  
Laura Marks ◽  
Evan Schwarz ◽  
David Liss ◽  
Munigala Satish ◽  
David K Warren ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Hospital Readmissions ◽  
Treatment Strategies ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Readmission Rates ◽  
Persons Who Inject Drugs ◽  
Increased Risk ◽  
Hospital Patients ◽  
The Impact

Abstract Background Persons who inject drugs (PWID) with opioid use disorder (OUD) are at increased risk of invasive bacterial and fungal infections, which warrant prolonged, inpatient parenteral antimicrobial therapy. Such admissions are complicated by opioid cravings and withdrawal. Comparisons of medications for OUD during prolonged admissions for these patients have not been previously reported. The aim of this study was to evaluate the impact of different OUD treatment strategies in this population, and their impact on ED and hospital readmissions. Methods We retrospectively analyzed consecutive admissions for invasive bacterial or fungal infections in PWID, admitted between January 2016 and January 2019 at Barnes-Jewish Hospital. Patients in our cohort were required to receive an infectious diseases consult, and an anticipated antibiotic treatment duration of >2 weeks. We collected data on demographics, comorbidities, length of stay, microbiologic data, medications prescribed for OUD, mortality, and readmission rates. We compared 90-day readmission rates by OUD treatment strategies using Kaplan–Meier curves. Results In our cohort of 237 patients, treatment of OUD was buprenorphine (17.5%), methadone (25.3%), or none (56.2%). Among patients receiving OUD treatment, 30% had methadone tapers and/or methadone discontinued upon discharge. Patient demographics were similar for each OUD treatment strategy. Infection with HIV (2.8%), and hepatitis B (3%), and hepatitis C (67%) were similar between groups. Continuation of medications for OUD was associated with increased completion of parenteral antibiotics (odds ratio 2.11; 95% confidence interval 1.70–2.63). When comparing medications for OUD strategies, methadone had the lowest readmission rates, followed by buprenorphine, and no treatment (P = 0.0013) (figure). Discontinuation of methadone during the admission or upon discharge was associated with the highest readmission rates. Conclusion Continuation of OUD treatment without tapering, was associated with improved completion of parenteral antimicrobials in PWID with invasive bacterial or fungal infections lower readmission rates. Tapering OUD treatment during admission was associated with higher readmission rates. Disclosures All authors: No reported disclosures.

scholarly journals A double-edged sword of using opioids and COVID-19: a toxicological view

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Mahshid Ataei ◽  
Farshad M. Shirazi ◽  
Roland J. Lamarine ◽  
Samaneh Nakhaee ◽  
Omid Mehrpour
Keyword(s):  
Organ Damage ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Inflammatory Phase ◽  
Clinical Support ◽  
Increased Risk ◽  
The World ◽  
Chronic Opioid Use ◽  
High Doses ◽  
World Information

AbstractToday, COVID-19 is spreading around the world. Information about its mechanism, prognostic factors, and management is minimal. COVID-19, as a human disease, has several identifying phases. Physicians of patients with COVID-19 may be interested in knowing whether opioid use disorder may affect their patients’ course or prognosis. This information may be crucial when considering the opioid epidemic in the US and other parts of the world. Opioid use at high doses and over several months duration can mitigate the immune system’s function, which may complicate the course of COVID-19 disease. Potential suppression of parts of the immune response may be important in prevention, clinical support, and therapeutic use of medications in various phases of the COVID-19. Specifically, opioid use disorders via an inhalation route may enhance the “late hyper-inflammatory phase” or result in end-organ damage. It is well established that opioids decrease ventilation as their effect on the medullary respiratory centers increases the risk of pneumonia. This increased risk has been associated with immune-suppressive opioids. The ultimate role of opioids in COVID-19 is not clear. This paper endorses the need for clinical studies to decipher the role and impact of chronic opioid use on viral diseases such as COVID-19.

Implications of the Opioid Crisis for the American Disability Community

2020 ◽  
Vol 34 (4) ◽  
pp. 265-274
Author(s):  
Mykal J. Leslie ◽  
Kathleen Sheppard-Jones ◽  
Malachy L. Bishop
Keyword(s):  
United States ◽  
Rehabilitation Counseling ◽  
The United States ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Research Education ◽  
Opioid Crisis ◽  
Increased Risk ◽  
The Relationship

PurposeThe profession of rehabilitation counseling has long been responsive to emerging disabilities. To date, however, the profession's attention and response to the ongoing opioid crisis in the United States has been incommensurate with the scope and detriment of opioids and opioid use disorder (OUD) on Americans with disabilities. The opioid crisis, including the overuse, abuse, and overdose rates associated with prescription and illegal opioids, affects people of all ages and backgrounds. However, people with disabilities are at increased risk for developing OUDs, and they experience greater barriers to OUD treatment than people without disabilities.MethodThis article describes the origins and development of this crisis, the relationship between disability and increased risk for OUD, and the barriers to treatment that exist. We then evaluate the role of rehabilitation counseling, including the need for further action in advocacy, research, education, and policy.Results and ConclusionsThroughout this article, we encourage a more urgent and concerted response than seems to be the case presently.

Punitive discontinuation of opioid agonist therapy during incarceration

2020 ◽  
Vol 16 (4) ◽  
pp. 337-342
Author(s):  
Allison Marmel ◽  
Nikki Bozinoff
Keyword(s):  
Case Report ◽  
Significant Risk ◽  
Opioid Use Disorder ◽  
Considerable Proportion ◽  
Opioid Use ◽  
Agonist Therapy ◽  
Opioid Agonist ◽  
Content Type ◽  
Opioid Agonist Therapy ◽  
Increased Risk

Purpose The prevalence of substance use disorders among incarcerated individuals in Canada is substantially higher than in the general population. Many incarcerated individuals with opioid use disorder remain untreated due to inadequate access to opioid agonist therapy (OAT). A considerable proportion of overdose-related deaths in the province of Ontario are individuals who have recently been released from prison. The purpose of this paper is to highlight that discontinuation of OAT as a disciplinary measure remains an active concern within prisons in Canada and places individuals with opioid use disorder at increased risk of relapse and resultant overdose death. Design/methodology/approach This case report describes an incarcerated client with opioid use disorder who was initially stable on OAT, but was forcibly tapered off OAT as a disciplinary measure and subsequently relapsed to illicit opioid use while in custody. Findings This case calls attention to concerns regarding treatment of opioid use disorder during incarceration, as forcible detoxification from OAT as a disciplinary measure is a highly dangerous practice. The authors discuss concerns regarding diversion and ways in which prison-based OAT programs can be improved to increase their safety and acceptability among correctional staff. Ongoing advocacy is required on the part of health-care workers and policymakers to ensure that individuals are able to appropriately access this life-saving therapy while incarcerated. Originality/value To the best of the authors’ knowledge, this is the first case report to describe forcible tapering of OAT as a disciplinary measure during incarceration. Despite existing evidence emphasizing the significant risk of overdose associated with detoxification from opioids, this case highlights the need for further research into the causes and prevalence of this practice.

scholarly journals A pilot study of the functionality and clinician acceptance of a clinical decision support tool to improve primary care of opioid use disorder

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Rebecca C. Rossom ◽  
JoAnn M. Sperl-Hillen ◽  
Patrick J. O’Connor ◽  
A. Lauren Crain ◽  
Laurel Nightingale ◽  
...  
Keyword(s):  
Primary Care ◽  
Decision Support ◽  
Clinical Decision Support ◽  
Clinical Decision ◽  
Primary Care Providers ◽  
Opioid Use Disorder ◽  
Care Providers ◽  
Opioid Use ◽  
Convenience Sample ◽  
Increased Risk

Abstract Objective Most Americans with opioid use disorder (OUD) do not receive indicated medical care. A clinical decision support (CDS) tool for primary care providers (PCPs) could address this treatment gap. Our primary objective was to build OUD-CDS tool and demonstrate its functionality and accuracy. Secondary objectives were to achieve high use and approval rates and improve PCP confidence in diagnosing and treating OUD. Methods A convenience sample of 55 PCPs participated. Buprenorphine-waivered PCPs (n = 8) were assigned to the intervention. Non-waivered PCPs (n = 47) were randomized to intervention (n = 24) or control (n = 23). Intervention PCPs received access to the OUD-CDS, which alerted them to patients at potentially increased risk for OUD or overdose and guided diagnosis and treatment. Control PCPs provided care as usual. Results The OUD-CDS was functional and accurate following extensive multi-phased testing. PCPs used the OUD-CDS in 5% of encounters with at-risk patients, far less than the goal of 60%. OUD screening confidence increased for all intervention PCPs and OUD diagnosis increased for non-waivered intervention PCPs. Most PCPs (65%) would recommend the OUD-CDS and found it helpful with screening for OUD and discussing and prescribing OUD medications. Discussion PCPs generally liked the OUD-CDS, but use rates were low, suggesting the need to modify CDS design, implementation strategies and integration with existing primary care workflows. Conclusion The OUD-CDS tool was functional and accurate, but PCP use rates were low. Despite low use, the OUD-CDS improved confidence in OUD screening, diagnosis and use of buprenorphine. NIH Trial registration NCT03559179. Date of registration: 06/18/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03559179

A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome

2021 ◽  
Author(s):  
Ayesha Sujan ◽  
Emma Cleary ◽  
Edie Douglas ◽  
Rubin Aujla ◽  
Lisa Boyars ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Clinical Sample ◽  
Opioid Use Disorder ◽  
Additional Benefit ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Opioid Use ◽  
Relative Safety ◽  
Increased Risk ◽  
Exposure During Pregnancy

Abstract Objectives The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications—methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS). Methods In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine. Results Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant. Conclusions Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS.

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