scholarly journals The 5α-reductase inhibitor finasteride reduces opioid self-administration

2020 ◽  
Author(s):  
Gabriel D. Bosse ◽  
Roberto Cadeddu ◽  
Gabriele Floris ◽  
Ryan D. Farero ◽  
Eva Vigato ◽  
...  
Keyword(s):  
Reductase Inhibitor ◽  
Antinociceptive Effect ◽  
Dehydroepiandrosterone Sulfate ◽  
Opioid Use Disorder ◽  
Therapeutic Strategies ◽  
Prostatic Hyperplasia ◽  
Opioid Use ◽  
Self Administration ◽  
The Us ◽  
Selection Of

AbstractOpioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify novel potential treatments for OUD, we screened a targeted selection of over 100 drugs, using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride did not interfere with the antinociceptive effect of opioids in rat models of neuropathic pain. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish, in a fashion akin to the effects of finasteride. Our results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new option for this disorder.

scholarly journals The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder

2021 ◽  
Author(s):  
Gabriel D. Bosse ◽  
Roberto Cadeddu ◽  
Gabriele Floris ◽  
Ryan D. Farero ◽  
Eva Vigato ◽  
...  
Keyword(s):  
Animal Models ◽  
Reductase Inhibitor ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Self Administration

scholarly journals Methadone Distribution Trends from 2017-2019 in the United States

2020 ◽  
Author(s):  
John A. Furst ◽  
Nicholas J. Mynarski ◽  
Kenneth L. McCall ◽  
Brian J. Piper
Keyword(s):  
United States ◽  
Rhode Island ◽  
Distribution Patterns ◽  
The United States ◽  
Opioid Use Disorder ◽  
Primary Objective ◽  
Treatment Programs ◽  
Opioid Use ◽  
Drug Enforcement ◽  
The Us

AbstractObjectiveMethadone is an evidence based treatment for opioid use disorder and is also employed for acute pain. The primary objective of this study was to explore methadone distribution patterns between the years 2017 and 2019 across the United States (US). This study builds upon previous literature that has analyzed prior years of US distribution patterns, and further outlines regional and state specific methadone trends.MethodsThe Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS) was used to acquire the number of narcotic treatment programs (NTPs) per state and methadone distribution weight in grams. Methadone distribution by weight, corrected for state populations, and number of NTPs were compared from 2017 to 2019 between states, within regions, and nationally.ResultsBetween 2017 and 2019, the national distribution of methadone increased 12.30% for NTPs but decreased 34.57% for pain, for a total increase of 2.66%. While all states saw a decrease in distribution for pain, when compared regionally, the Northeast showed a significantly smaller decrease than all other regions. Additionally, the majority of states experienced an increase in distribution for NTPs and most states demonstrated a relatively stable or increasing number of NTPs, with an 11.49% increase in NTPs nationally. The number of NTPs per 100K in 2019 ranged from 2.08 in Rhode Island to 0.00 in Wyoming.ConclusionAlthough methadone distribution for OUD was increasing in the US, there were pronounced regional disparities.

scholarly journals Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

2020 ◽  
Author(s):  
Aaron J Salisbury ◽  
Christopher A Blackwood ◽  
Jean Lud Cadet
Keyword(s):  
Glutamate Receptors ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Opioid Use Disorder ◽  
Mrna Levels ◽  
Opioid Use ◽  
Self Administration ◽  
Lever Pressing ◽  
Polymerase Chain ◽  
Long Access

People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6 and Grm8 subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

Use of Buprenorphine for the Treatment of Opioid Use Disorder

2020 ◽  
pp. 155-168
Author(s):  
Paul J. Fudala ◽  
Anne Cramer Andorn
Keyword(s):  
Opioid Dependence ◽  
Addiction Treatment ◽  
Partial Agonist ◽  
The United States ◽  
Opioid Use Disorder ◽  
Sublingual Administration ◽  
Opioid Use ◽  
The Us ◽  
Monthly Administration ◽  
Drug Addiction Treatment

Buprenorphine is a mu-opioid partial agonist that was first developed as a parenteral analgesic and subsequently as a treatment for opioid dependence. In the United States, the first two products approved by the US Food and Drug Administration (in 2002) for the latter indication were buprenorphine (Subutex) and buprenorphine/naloxone (Suboxone) tablet formulations for sublingual administration. Since that time, additional products for both sublingual and buccal administration have also been approved, as well as a subcutaneous injection for once-monthly administration for the treatment of moderate or severe opioid use disorder (OUD) and a subdermal implant for the maintenance treatment of opioid dependence that delivers buprenorphine over a 6-month period. Under the Drug Addiction Treatment Act of 2000 (DATA 2000), qualified practitioners may apply for waivers to treat opioid dependence/OUD with approved buprenorphine products in any setting in which they are qualified to practice. Like other opioids, buprenorphine has the potential for being misused and abused.

scholarly journals Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA–GABA transmission in highly addicted rats

2020 ◽  
Vol 117 (4) ◽  
pp. 2140-2148 ◽  
Author(s):  
Marsida Kallupi ◽  
Lieselot L. G. Carrette ◽  
Jenni Kononoff ◽  
Leah C. Solberg Woods ◽  
Abraham A. Palmer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Opioid Use Disorder ◽  
Central Nucleus ◽  
Orphanin Fq ◽  
Opioid Use ◽  
Self Administration ◽  
Endogenous Opioid ◽  
Electrophysiological Recordings ◽  
Gaba Transmission

Approximately 25% of patients who are prescribed opioids for chronic pain misuse them, and 5 to 10% develop an opioid use disorder. Although the neurobiological target of opioids is well known, the molecular mechanisms that are responsible for the development of addiction-like behaviors in some but not all individuals are poorly known. To address this issue, we used a unique outbred rat population (heterogeneous stock) that better models the behavioral and genetic diversity that is found in humans. We characterized individual differences in addiction-like behaviors using an addiction index that incorporates the key criteria of opioid use disorder: escalated intake, highly motivated responding, and hyperalgesia. Using in vitro electrophysiological recordings in the central nucleus of the amygdala (CeA), we found that rats with high addiction-like behaviors (HA) exhibited a significant increase in γ-aminobutyric acid (GABA) transmission compared with rats with low addiction-like behaviors (LA) and naive rats. The superfusion of CeA slices with nociceptin/orphanin FQ peptide (N/OFQ; 500 nM), an endogenous opioid-like peptide, normalized GABA transmission in HA rats. Intra-CeA levels of N/OFQ were lower in HA rats than in LA rats. Intra-CeA infusions of N/OFQ (1 μg per site) reversed the escalation of oxycodone self-administration in HA rats but not in LA rats. These results demonstrate that the downregulation of N/OFQ levels in the CeA may be responsible for hyper-GABAergic tone in the CeA that is observed in individuals who develop addiction-like behaviors. Based on these results, we hypothesize that small molecules that target the N/OFQ system might be useful for the treatment of opioid use disorder.

scholarly journals Factors Associated with Prescription Opioid Analgesic Use in the US Population, 2011–2014

Pain Medicine ◽  
2018 ◽  
Vol 20 (7) ◽  
pp. 1338-1346 ◽  
Author(s):  
Steven M Frenk ◽  
Susan L Lukacs ◽  
Qiuping Gu
Keyword(s):  
Opioid Analgesic ◽  
Opioid Analgesics ◽  
Opioid Use Disorder ◽  
Prescription Opioid ◽  
Opioid Use ◽  
Factors Associated ◽  
The Past ◽  
The Us ◽  
Opioid Users ◽  
Analgesic Use

Abstract Objective This study examined factors associated with prescription opioid analgesic use in the US population using data from a nationally representative sample. It focused on factors previously shown to be associated with opioid use disorder or overdose. Variations in the use of different strength opioid analgesics by demographic subgroup were also examined. Methods Data came from respondents aged 16 years and older who participated in the National Health and Nutrition Examination Survey (2011–2014). Respondents were classified as opioid users if they reported using one or more prescription opioid analgesics in the past 30 days. Results Opioid users reported poorer self-perceived health than those not currently using opioids. Compared with those not using opioids, opioid users were more likely to rate their health as being “fair” or “poor” (40.4% [95% confidence interval {CI} = 34.9%–46.2%] compared with 15.6% [95% CI = 14.3%–17.1%]), experienced more days of pain during the past 30 days (mean = 14.3 [95% CI = 12.9–15.8] days compared with 2.3 [95% CI = 2.0–2.7] days), and had depression (22.5% [95% CI = 17.3%–28.7%] compared with 7.1% [95% CI = 6.2%–8.0%]). Among those who reported using opioids during the past 30 days, 18.8% (95% CI = 14.4%–24.1%) reported using benzodiazepine medication during the same period and 5.2% (95% CI = 3.5%–7.7%) reported using an illicit drug during the past six months. When opioid strength was examined, a smaller percentage of adults aged 60 years and older used stronger-than-morphine opioids compared with adults aged 20–39 and 40–59 years. Conclusions Higher percentages of current opioid users than nonusers reported having many of the factors associated with opioid use disorder and overdose.

scholarly journals Network-Based Discovery of Opioid Use Vulnerability in Rats Using the Bayesian Stochastic Block Model

2021 ◽  
Author(s):  
Carter Allen ◽  
Brittany N Kuhn ◽  
Nazzareno Cannella ◽  
Ayteria D Crow ◽  
Analyse T Roberts ◽  
...  
Keyword(s):  
Progressive Ratio ◽  
Opioid Use Disorder ◽  
Heroin Addiction ◽  
Opioid Use ◽  
Self Administration ◽  
Block Model ◽  
Similarity Network ◽  
Stochastic Block Model ◽  
Analysis Workflow ◽  
Reinstatement Test

Opioid use disorder is a psychological condition that affects over 200,000 people per year in the U.S., causing the Centers for Disease Control and Prevention to label the crisis as a rapidly spreading public health epidemic. It has been found that the behavioral relationship between opioid exposure and development of opioid use disorder varies greatly between individuals, implying existence of sup-populations with varying degrees of opioid vulnerability. In this study, we assessed several behavioral variables across heroin taking, refraining and seeking to establish how these factors interact with one another resulting in a heroin dependent, resilient, or vulnerable behavioral phenotype. Over 400 (male and female) heterogeneous stock rats were used in these two studies, and data were collected from two geographically distinct locations. Rats underwent heroin self-administration training, followed by a progressive ratio and heroin-primed reinstatement test. Next, rats underwent extinction training and a cue-induced reinstatement test. To assess how these variables contribute to heroin addiction vulnerability, we developed a network-based data analysis workflow. Specifically, we integrated different cohorts of rats, remove possible batch effects, and constructed a rat-rat similarity network based on their behavioral patterns. We then implemented community detection on this similarity network using a Bayesian degree-corrected stochastic block model to uncover sub-populations of rats with differing levels of opioid vulnerability. We discovered three distinct behavioral sub-populations, each with significantly different behavioral outcomes that allowed for unique characterization of each cluster in terms of vulnerability to opioid use and seeking. We implement this analysis workflow as an open source R package, named mlsbm.

scholarly journals Accessibility to Medication for Opioid Use Disorder After Interventions to Improve Prescribing Among Nonaddiction Clinics in the US Veterans Health Care System

2021 ◽  
Vol 4 (12) ◽  
pp. e2137238
Author(s):  
Eric J. Hawkins ◽  
Carol A. Malte ◽  
Adam J. Gordon ◽  
Emily C. Williams ◽  
Hildi J. Hagedorn ◽  
...  
Keyword(s):  
Health Care ◽  
Health Care System ◽  
Opioid Use Disorder ◽  
Veterans Health ◽  
Opioid Use ◽  
The Us ◽  
Us Veterans ◽  
Care System
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