Development Of Opioid Use Disorder Research Articles

Opioids and the hormone oxytocin.

The neuropeptide Oxytocin (ΟΤ) is involved as a neurohormone, a neurotransmitter, or a neuromodulator in an extensive range of central and peripheral effects, complex emotional and social human behaviors, memory and learning processes. It is implicated in homeostatic, neuroadaptive processes associated with stress responses and substance use via interactions with the hypothalamic-pituitary-adrenal (HPA) axis and the dopamine mesolimbic reward stress system. This chapter reviews the preclinical and clinical literature on the complicated relationships between endogenous and exogenous opioids and ΟΤ systems and attempts to highlight key findings to date on the effectiveness of intranasal OT administration to treat opioid use disorders. OΤ seems to attenuate, even inhibit, the development of opioid use disorders in preclinical models but is still under clinical research as a promising pharmacological agent in the treatment of opioid use related behaviors. Evidence suggests a role for OT as an adjunctive or stand-alone treatment of behavioral, cognitive and emotional deficits associated with substance use, which may be responsible for seeking behavior and relapse. The mechanisms by which oxytocin acts to reverse the neural substrates of these deficits, partially due to substance induced alterations of the endogenous OT system, and thus modify the behavioral response to substance use are discussed. Other clinically relevant issues are also discussed.

100: Effects of lactation on susceptibility to opioid dependence in the chemically-naive subject

Prescription and illicit opioid misuse, overdose, and the development of opioid use disorder (OUD) are pressing problems globally. This class of drugs acts through opioid receptors expressed within the corticostriatal circuitry underlying reward processing. For many women, their first exposure to opioids is following childbirth. Oxytocin has also been shown to have a role in reward processes. We investigated the hypothesis that lactation in female mice impacts brain expression of OPRs and related proteins. After delivery female B629SF2/J mice were randomized into lactated (L, n=10-16) and non-lactated (NL, n=10-12) groups. In the L group, dams breastfed their pups until they were 21 days old. In the NL group, the dams were separated from their pups within 24 hours of birth. Dams were sacrificed at 6 months postpartum and their brain cortex isolated. Expression of the following genes involved in neural pathways which are implicated in the development of OUD was determined using quantitative real time RT-PCR: brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), mu-opioid receptor (OPRM1), delta-opioid receptor (OPRD1), proenkephalin (PENK), and tyrosine hydroxylase (TH). GAPDH was used as control. Statistical analyses were performed using Student t or Mann-Whitney tests as appropriate (statistical significance P < .05). The OPRM1 receptor levels were significantly lower in L compared to NL dams (P=0.03, Fig). Elevated levels of OPRM1 have been found in chronic substance abusers and in those in craving states for substances of abuse. OPRD1 levels were significantly higher in L compared to NL mice (P=0.02, Fig). OPRD1 receptors have been associated with inhibition of impulsivity. The higher levels of OPRD1 found in L dams may imply a lesser susceptibility to the effects of substances of abuse. No other differences were found. By decreasing OPRM1 levels and increasing OPRD1 levels in the cortex, lactation may have a long-lasting protective effect against the development of OUD. Additional studies to determine the mechanisms for this protective effect and the role of oxytocin signaling are warranted.

Chronic pain management and the development of opioid use disorder

Chronic pain is a common condition that impacts quality of life and often precipitates the need for medical attention. Despite evidence that long-term opioid use provides limited relief, prescription opioid therapy remains a cornerstone in the medical management of chronic non-cancer pain. Presently, 13% of Canadians are prescribed opioids for pain management, and physicians play a crucial role in preventing the development of opioid use disorders. However, Canadian physicians lack knowledge of and comfort with evidence-based principles of opioid stewardship. In this article, we aim to highlight ongoing Canadian efforts to address physician discomfort and improve clinical practice. We focus on 2017 Canadian guidelines that provide clinicians with evidence-based recommendations for opioid use in chronic non-cancer pain management. In addition, we call attention to provincial efforts to implement physician accountability measures. In reviewing the existing literature, we uncovered inadequacies in pain management curricula within the Canadian undergraduate and continuing medical education (CME) systems. We consulted the educational practices of the European Pain Federation and the Centers for Disease Control and Prevention to make recommendations for improvement to current Canadian pain curricula. Based on our findings, we recommend that (1) Canadian medical institutions expand upon current core pain curricula, (2) pain management education be made compulsory, (3) academic detailing be emphasized as a means of CME, and (4) multidisciplinary non-medical management of chronic pain be featured more extensively.

Improving the Safety of Opioid Use for Acute Noncancer Pain in Hospitalized Adults: A Consensus Statement From the Society of Hospital Medicine.

Hospital-based clinicians frequently treat acute, noncancer pain. Although opioids may be beneficial in this setting, the benefits must be balanced with the risks of adverse events, including inadvertent overdose and prolonged opioid use, physical dependence, or development of opioid use disorder. In an era of epidemic opioid use and related harms, the Society of Hospital Medicine (SHM) convened a working group to develop a consensus statement on opioid use for adults hospitalized with acute, noncancer pain, outside of the palliative, end-of-life, and intensive care settings. The guidance is intended for clinicians practicing medicine in the inpatient setting (eg, hospitalists, primary care physicians, family physicians, nurse practitioners, and physician assistants). To develop the Consensus Statement, the working group conducted a systematic review of relevant guidelines, composed a draft Statement based on extracted recommendations, and obtained feedback from external experts in hospital-based opioid prescribing, SHM members, the SHM Patient-Family Advisory Council, other professional societies, and peer-reviewers. The iterative development process resulted in a final Consensus Statement consisting of 16 recommendations covering 1) whether to use opioids in the hospital, 2) how to improve the safety of opioid use during hospitalization, and 3) how to improve the safety of opioid prescribing at hospital discharge. As most guideline recommendations from which the Consensus Statement was derived were based on expert opinion alone, the working group identified key issues for future research to support evidence-based practice.

Associations of anabolic-androgenic steroid use with other behavioral disorders: an analysis using directed acyclic graphs.

Anabolic-androgenic steroid (AAS) use is known to be associated with other psychiatric disorders, such as body image disorders, conduct disorder/sociopathy, and other substance use disorders (SUD) - but the causal pathways among these conditions remain poorly delineated. We created a directed acyclic graph to diagram hypothesized relationships among AAS use and dependence, body image disorder (BID), conduct disorder/sociopathy, and other SUD. Using proportional hazards models, we then assessed potentially causal relationships among these variables, using a dataset of 233 male weightlifters, of whom 102 had used AAS. BID and conduct disorder/sociopathy both strongly contributed to the development of AAS use, but did not appear to contribute further to the progression from AAS use to AAS dependence. Other SUD beginning prior to first AAS use - whether broadly defined or restricted only to opioids - failed to show an effect on AAS use or progression to AAS dependence. Conversely, AAS use contributed significantly to the subsequent first-time development of opioid use disorders but did not significantly increase the risk for first-time development of non-opioid SUD, taken as a whole. Our analysis suggests that AAS use and other SUD are mutually attributable to underlying conduct disorder/sociopathy. SUD do not appear to represent a 'gateway' to subsequent AAS use. AAS use may represent a gateway to subsequent opioid use disorder, but probably not to other SUD.

Screening in Trauma for Opioid Misuse Prevention (STOMP): study protocol for the development of an opioid risk screening tool for victims of injury

BackgroundOpioid addiction and overdose are epidemic in the U.S. Victims of traumatic injury are at greater than average risk for opioid misuse and related complications. Potential risk screens and preventive interventions in this clinical population remain under-investigated. The current project seeks to develop and pilot the implementation of a screening tool for opioid risk at American College of Surgeons (ACS) Level I and Level II trauma centers.MethodsThe project began with an online survey, which was sent to Wisconsin trauma center medical directors and trauma coordinators for the purpose of gathering information on current substance use screening practices. Next, a focus group of trauma center staff was convened to discuss barriers and facilitators to screening, resources available and needed to support trauma patients with opioid use disorders, and measurable clinical observations that could indicate a patient’s potential risk for opioid misuse. Data from the surveys and focus group were combined to inform the data collection instruments that are currently being administered to patients recruited from the University of Wisconsin Hospital Trauma Inpatient and Orthopedic Surgery Services. Eligible and consenting patients complete standardized measures of socio-demographics, substance use history, opioid misuse risk, mental health, medical history, and injury and pain severity. Follow up visits at weeks 4, 12, and 24 after hospital discharge assess hypothesized risk factors for opioid addiction and opioid use disorder diagnosis. At the completion of patient data collection, a forward stepwise regression will identify factors of most significant risk of the development of opioid use disorder after traumatic injury. This modeling will inform the development of a novel opioid risk screening tool, which will undergo pilot implementation at 4 Wisconsin ACS Level I and Level II trauma centers, using an evidence-based implementation strategy with roots in systems engineering.DiscussionPositive findings from the proposed work would lead to improved, standardized opioid risk screening practices among victims of traumatic injury. The ultimate goal of this and future work is to reduce the likelihood of opioid misuse, addiction, and related complications, such as overdose and death.Trial registration Clinicaltrials.gov registration number: NCT02861976. Date of registration: Feb 9, 2016

Opioid Treatment Agreements: Helpful or Hurtful?

Opioid Treatment Agreements: Helpful or Hurtful?

Factors predicting development of opioid use disorders among individuals who receive an initial opioid prescription: Mathematical modeling using a database of commercially-insured individuals

BackgroundPrescription drug abuse in the United States and elsewhere in the world is increasing at an alarming rate with non-medical opioid use, in particular, increasing to epidemic proportions over the past two decades. It is imperative to identify individuals most likely to develop opioid abuse or dependence to inform large-scale, targeted prevention efforts. MethodsThe present investigation utilized a large commercial insurance claims database to identify demographic, mental health, physical health, and healthcare service utilization variables that differentiate persons who receive an opioid abuse or dependence diagnosis within two years of filling an opioid prescription (OUDs) from those who do not receive such a diagnosis within the same time frame (non-OUDs). ResultsWhen compared to non-OUDs, OUDs were more likely to: (1) be male (59.9% vs. 44.2% for non-OUDs) and younger (M=37.9 vs. 47.7); (2) have a prescription history of more opioids (1.7 vs. 1.2), and more days supply of opioids (M=272.5, vs. M=33.2; (3) have prescriptions filled at more pharmacies (M=3.3 per year vs. M=1.3); (4) have greater rates of psychiatric disorders; (5) utilize more medical and psychiatric services; and (6) be prescribed more concomitant medications. A predictive model incorporating these findings was 79.5% concordant with actual OUDs in the data set. ConclusionsUnderstanding correlates of OUD development can help to predict risk and inform prevention efforts.