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Opioid Abuse [keywords]
- Effect of mu-opioid agonist DAMGO on surface CXCR4 and HIV-1 replication in TF-1 human bone marrow progenitor cells. [JOURNAL ARTICLE]
- BMC Res Notes 2014 Oct 23; 7(1):752.
Approximately one-third of the AIDS cases in the United States have been attributed to the use of injected drugs, frequently involving the abuse of opioids. Consequently, it is critical to address whether opioid use directly contributes to altered susceptibility to HIV-1 beyond the increased risk of exposure. Previous in vitro and in vivo studies addressing the role of mu-opioid agonists in altering levels of the co-receptor CXCR4 and subsequent HIV-1 replication have yielded contrasting results. The bone marrow is believed to be a potential anatomical sanctuary for HIV-1.The well-characterized CD34+CD38+ human bone marrow-derived hematopoietic progenitor cell line TF-1 was used as a model to investigate the effects of the mu-opioid receptor-specific peptide DAMGO (D-Ala2,N-Me-Phe4,Gly5-ol-enkephalin) on CXCR4 expression as well as infection of undifferentiated human hematopoietic progenitor cells.The results revealed the presence of the mu-opioid receptor-1 isoform (MOR-1) on the surface of TF-1 cells. Furthermore, immunostaining revealed that the majority of TF-1 cells co-express MOR-1 and CXCR4, and a subpopulation of these double-positive cells express the two receptors in overlapping membrane domains. Three subpopulations of TF-1 cells were categorized based on their levels of surface CXCR4 expression, defined as non-, low-, and high-expressing. Flow cytometry indicated that treatment with DAMGO resulted in a shift in the relative proportion of CXCR4+ cells to the low-expressing phenotype. This result correlated with a >3-fold reduction in replication of the X4 HIV-1 strain IIIB, indicating a role for the CXCR4 high-expression subpopulation in sustaining infection within this progenitor cell line.These experiments provide insight into the impact of mu-opioid exposure with respect to inhibition of viral replication in this human TF-1 bone marrow progenitor cell line model.
- Palliative Sedation for Status Epilepticus in a Patient with Progressive Multifocal Leukoencephalopathy. [JOURNAL ARTICLE]
- J Pain Palliat Care Pharmacother 2014 Oct 22.
ABSTRACT Palliative sedation is defined as the use of sedative drugs in order to reduce the patient's consciousness in case of refractory symptoms. The most used drug is midazolam, a benzodiazepine with a short half-life administered either intravenously or subcutaneously. We discuss on a clinical case requiring an exceptionally high dosage of midazolam-up to 160 mg iv daily-to achieve palliative sedation. The patient was an HIV positive 29-year-old male who was suffering from progressive multifocal leukoencephalopathy complicated by a refractory status epilepticus and who was suspected of previous benzodiazepines and opioid abuse. In such situations of a suffering brain doses of midazolam to achieve symptom control may be much higher than expected.
- Sexual dysfunction in patients with alcohol and opioid dependence. [Journal Article, Review]
- Indian J Psychol Med 2014 Oct; 36(4):355-65.
There are limited numbers of studies which have evaluated the sexual dysfunction (SD) in patients with alcohol and opioids dependence. This article reviews the existing literature. Electronic searches were carried out using the PubMed, Google Scholar, and ScienceDirect to locate the relevant literature. Subjects addicted to heroin or on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT) show higher rates of SD in comparison to the general population. SD rates have ranged 34-85% for heroin addicts, 14-81% for MMT, 36-83% for BMT, and 90% for naltrexone maintenance. The rates of SD in alcohol-dependent population have ranged 40-95.2%, with rates being consistently much higher in alcohol-dependent population than in the healthy controls or social drinkers. The common SDs reported have been erectile dysfunction followed by premature ejaculation, retarded ejaculation and decreased sexual desire among men, and dyspareunia and vaginal dryness among women. This review suggests that long-term use of alcohol and opioids are associated with SD in almost all domains of sexual functioning. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse. Further, there is a need to carry out more number of studies to understand the relationship in a better way.
- Cannabis Use Disorders Predispose to the Development of Sexually Transmitted Diseases among Youth. [JOURNAL ARTICLE]
- Int J Med Biol Front 2012; 18(6):393-398.
Previous cross-sectional studies involving adults suggest that sexually transmitted diseases (STD) such as cocaine use disorders and opioid use disorders are associated with the development of sexually transmitted diseases (STD). However, it is less clear whether cannabis use disorders (CUD) are associated with the development of STDs, or whether those associations extend to adolescent populations. Longitudinal studies examining those associations are particularly scarce. The current report provides findings from a longitudinal study that examined the relationship between STD and CUD among youth transitioning to young adulthood.The subjects in this longitudinal study were initially recruited when the index sons of these fathers were 10-12 years of age, and subsequent assessments were conducted at age 12-14, 16, 19, and 22. Multivariate logistic regression and path analyses were conducted.At age 22, of the 345 subjects, 30 subjects were diagnosed with one or more STD, and 105 were diagnosed with a CUD. STDs were almost four times as common among those with a CUD as among those without a CUD, which was a significant difference. Path analyses demonstrated that peer deviance mediated the association between a measure of risk for SUD knows as the TLI and CUD, and that peer deviance mediated the association between TLI and STD. Risky sexual behaviors were common.These finding suggest that cannabis use disorders (CUD) predispose to the development of sexually transmitted disorders (STD) among youth. These findings also suggest that peer deviance mediates the development of STD and of CUD among teenagers making the transition to young adulthood.
- Sex Differences Among Opioid-Abusing Patients With Chronic Pain in a Clinical Trial. [JOURNAL ARTICLE]
- J Addict Med 2014 Oct 16.
The characteristics of patients with co-occurring chronic pain and prescription opioid abuse have not been well described, and even less is known about differences between men and women in this population.This study evaluated sex differences in the demographic, diagnostic, and behavioral attributes of patients with chronic pain and opioid abuse.Data were collected via self-report and semistructured clinical interviews from 162 patients (120 men and 42 women) who screened for a study investigating the abuse liability of prescription opioids.There were no differences between men and women in age, race, education, marital status, or employment status. Participants had used prescription opioids for 5.4 ± 6.7 years. The majority of participants (60%) had low back pain in addition to opioid dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. More women reported more arthritic pain than men, but otherwise there were no differences in types of pain. Pain exerted a greater effect in women on mood, walking ability, and social relations. Men reported more of certain aberrant behaviors, including abuse of alcohol or illicit drugs, unauthorized dose increases, contact with street culture, and being arrested by police. Women were more depressed than men.The demographic profile of opioid-abusing patients with chronic pain presenting for treatment in a clinical trial was similar between sexes; however, some important differences were observed. Women reported more psychiatric comorbidity and endorsed greater pain-related physical and social impairment. Men reported more aberrant behaviors. These differences suggest that men with chronic pain and opioid abuse/dependence may benefit by closer monitoring of aberrant behaviors whereas women may benefit from closer attention paid to physical and psychological effects of pain.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
- Opioid Neonatal Abstinence Syndrome: controversies and implications for practice. [JOURNAL ARTICLE]
- Curr Drug Abuse Rev 2014 Oct 15.
The Opioid Neonatal Abstinence Syndrome (NAS) is a term used to describe a cluster of signs and symptoms seen in infants experiencing withdrawal from opioid drugs. Despite a substantial literature the relationship between maternal methadone dose, NAS and the method of assessment of NAS symptoms has not been agreed. The following review will address current and historical controversies surrounding these issues and will examine the evidence concerned with the evaluation of neonates exposed to methadone in utero. The key findings are as follows: A variety of NAS scales are used to assess the severity of neonatal withdrawal symptoms including locally adapted validated tools. Inconsistencies in the use of NAS scales have included the timing, duration and frequency of administration; the degree to which observers were trained to reliability; the use of NAS scales designed for term neonates to assess pre-term neonates who may have a qualitatively different expression of abstinence symptoms and; the research setting in which the tool was administered. There is a lack of research investigating the observant bias' effect upon scoring NAS, the basis for treatment decisions and the influence of concomitant maternal use of non-opioid drugs late in pregnancy. We also discuss the implications of the lack of recognition of NAS symptoms leading to possible under reporting and inappropriate, early neonatal discharge from hospital. In addition, this paper also discusses the merits and problems of conducting research in this area and highlights gaps in our knowledge and areas for further research.
- Disposing of Medicines Safely. [JOURNAL ARTICLE]
- Am J Public Health 2014 Oct 16.:e1-e2.
We read with great interest the systematic review by King et al. analyzing opioid-related mortality in North America.(1) We believe pharmacy take-back programs are an approach that could help address this daunting epidemic. Inappropriate medicine use often arises from improper access. Most adolescents who abuse prescription drugs report obtaining them for free from a friend or relative, often without that person's knowledge.(2) To reduce access, we must remove unused and unneeded medicines from circulation and safely dispose of them. (Am J Public Health. Published online ahead of print October 16, 2014: e1-e2. doi:10.2105/AJPH.2014.302296).
- The G-protein biased k-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo. [JOURNAL ARTICLE]
- J Pharmacol Exp Ther 2014 Oct 15.
The hypothesis that functionally selective GPCR agonists may have enhanced therapeutic benefits has revitalized interest for many GPCR targets. In particular, although κ-opioid receptor (KOR) agonists are analgesic with a low risk of dependence and abuse, their utility is limited by a propensity to induce sedation, motor incoordination, hallucinations and dysphoria-like states. Several labs have produced a body of work implying that G-protein biased KOR agonists might be analgesic with fewer side-effects. Although this has been an intriguing hypothesis, suitably KOR selective and G-protein biased agonists have not been available to test this idea. Here we provide data using a G-protein biased agonist RB-64 which suggests that KOR-mediated G protein signaling induces analgesia and aversion, whereas β-arrestin 2 signaling may be associated with motor incoordination. Additionally, unlike unbiased KOR agonists, the G protein-biased ligand RB 64 does not induce sedation and does not have anhedonia-like actions, suggesting that a mechanism other than G protein signaling mediates these effects. Our findings provide the first evidence with a highly selective and G-protein biased tool compound that many, but not all, of the negative side effects of KOR agonists can be minimized by creating G protein biased KOR agonists.
- Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment. [JOURNAL ARTICLE]
- J Addict Med 2014 Oct 13.
Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
- Buprenorphine/Naloxone Dose and Pain Intensity Among Individuals Initiating Treatment for Opioid Use Disorder. [JOURNAL ARTICLE]
- J Subst Abuse Treat 2014 Sep 26.
Opioid use disorder and pain often co-occur, complicating the treatment of each condition. Owing to its partial agonist properties, buprenorphine/naloxone (BUP/NX) may confer advantages over full agonist opioids for treatment of both conditions. The optimal dose of BUP/NX for comorbid pain is not known. We examined dose and other factors associated with pain intensity among patients initiating BUP/NX for opioid use disorder.We studied 1106 patients initiating BUP/NX treatment for opioid use disorder from 2003 to 2010. Information on pain level, diagnoses, and treatment were extracted from medical records. Eligible patients had at least one self-reported pain intensity numerical rating score (NRS) within 30days before BUP/NX initiation (baseline) and at least one between 15 and 90days after BUP/NX initiation (during treatment). The primary outcome was NRS decrease (2 or greater) from baseline to during treatment. We used generalized estimating equations to model odds of the primary outcome with BUP/NX dose as the independent variable of interest in the subset of patients with a baseline NRS≥2.The sample was 94% male and 73% White. Mean age was 50. Psychiatric and non-opioid substance use comorbidities were common. The following demographic and clinical correlates were associated with a decrease in pain intensity: age 18-29 (compared to 30-39 and 40-49); absence of PTSD diagnosis and absence of a chronic pain diagnosis. BUP/NX dose was not associated with decreased pain intensity in bivariate or multivariable analysis.BUP/NX maintenance treatment was generally consistent with improvements in pain intensity; however, factors other than BUP/NX dose contribute to improved pain intensity among those initiating the medication.