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Opioid Abuse [keywords]
- Medication-assisted therapy for opioid addiction. [JOURNAL ARTICLE]
- J Food Drug Anal 2013 Dec; 21(4):S13-S15.
The "Medication-Assisted Therapy for Opioid Addiction" session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).
- Endogenous Opiates and Behavior: 2013. [REVIEW]
- Peptides 2014 Sep 25.
This paper is the thirty-sixth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2013 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).
- Measures to quantify the abuse of prescription opioids: a review of data sources and metrics. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Sep 25.
The abuse and nonmedical use of prescription opioids and its subsequent consequences are an important public health concern. This phenomenon has paralleled the increase in the therapeutic use of opioids for pain management. There is thus a need to measure prescription opioid abuse to understand trends over time and to compare abuse of one product to another. The purpose of this review is to provide an overview of the strengths and weaknesses of frequently used numerators and denominators in "abuse ratios" (ARs).For this review, we critically evaluated the various measures to quantify drug availability and the available data sources to measure prescription opioid abuse.There are currently no commonly adopted metrics for measuring either the prevalence of opioid abuse, or abuse relative to drug availability. Because the settings, manifestations, and severity of abuse can vary from one person to the next, no one measure of abuse, abuse-related outcome, or drug exposure is ideal. Each measure of abuse captures a specific facet of abuse, but not the whole spectrum. Reliable estimation of population-adjusted or utilization-adjusted rates of abuse can be accomplished with a prescription opioid AR. This metric estimates the prevalence of abuse in a given population or abuse relative to how much drug is available, and, in certain cases, can be used to compare abuse among various opioid drugs. AR measurements in the literature vary in the inclusion of specific measures of abuse and availability, and there is little consensus in the field regarding which measures allow for the most appropriate approximation of the extent of abuse, and for comparisons among opioids. Crude numbers of outcomes related to abuse (e.g., emergency department visits, treatment admissions, and overdoses) cannot be properly understood without context as these may overestimate or underestimate the true scope and severity of prescription opioid abuse. They can, however, serve as numerators in properly constructed ARs. The denominator of the AR provides the necessary context by accounting for populations at risk or drug availability (e.g., prescriptions or tablets dispensed, unique recipients of dispensed drug, total patient days of therapy, or kilograms sold), and each comes with its own set of assumptions to consider.Moving forward, it is important that there be a common understanding in the scientific community regarding how to select appropriate measures to serve as numerators and denominators in AR calculations, and how to interpret the resultant findings. There is no single best measure of abuse for use as a numerator in an AR, and each must be chosen and interpreted in the context of what it measures. For public health considerations, one must always look at both absolute numbers and adjusted numbers. When conducting multiple analyses using different measures of exposure as denominators, differences in ARs are not unexpected, but one should explore why there are differences and assess the appropriateness of each of the denominators. Copyright © 2014 John Wiley & Sons, Ltd.
- Novel approaches for the treatment of psychostimulant and opioid abuse - focus on opioid receptor-based therapies. [JOURNAL ARTICLE]
- Expert Opin Drug Discov 2014 Sep 25.:1-12.
Introduction: Psychostimulant and opioid addiction are poorly treated. The majority of abstinent users relapse back to drug-taking within a year of abstinence, making 'anti-relapse' therapies the focus of much current research. There are two fundamental challenges to developing novel treatments for drug addiction. First, there are three key stimuli that precipitate relapse back to drug-taking: stress, presentation of drug-conditioned cue, taking a small dose of drug. The most successful novel treatment would be effective against all three stimuli. Second, a large number of drug users are poly-drug users: taking more than one drug of abuse at a time. The ideal anti-addiction treatment would, therefore, be effective against all classes of drugs of abuse. Areas covered: In this review, the authors discuss the clinical need and animal models used to uncover potential novel treatments. There is a very broad range of potential treatment approaches and targets currently being examined as potential anti-relapse therapies. These broadly fit into two categories: 'memory-based' and 'receptor-based' and the authors discuss the key targets here within. Expert opinion: Opioid receptors and ligands have been widely studied, and research into how different opioid subtypes affect behaviours related to addiction (reward, dysphoria, motivation) suggests that they are tractable targets as anti-relapse treatments. Regarding opioid ligands as novel 'anti-relapse' medication targets, research suggests that a 'non-selective' approach to targeting opioid receptors will be the most effective.
- Suicide by means of opioid overdose in patients with chronic pain. [Journal Article]
- Curr Pain Headache Rep 2014 Nov; 18(11):460.
Deaths from prescription opioid use continue to rise in North America. The main focus to date has been developing strategies to prevent nonintentional (accidental) fatalities, which constitute the majority of opioid deaths across all jurisdictions. Often overlooked is the complex group of individuals whose cause of death was suicide by opioid overdose. Although most opioid prescribing tools focus on identifying risk factors for potential abuse, diversion, and propensity for opioid addiction, physicians who consider prescribing opioids should also screen and optimize chronic pain treatment for patients at risk for suicide.
- Chronic opioid therapy for chronic non-cancer pain: a review and comparison of treatment guidelines. [Journal Article]
- Pain Physician 2014 Sep-Oct; 17(5):401-14.
Long-term opioid use for chronic non-cancer pain has increased substantially in recent years despite the paucity of strong supporting scientific data and concerns regarding adverse effects and potential misuse.Review and summary of practice guidelines available on PubMed and Cochrane databases as well as on the Internet on chronic opioid therapy from June 2004 to June 2013.To review expert-developed practice guidelines on chronic opioid therapy, published in different countries over the past decade in order to reveal similar principles of therapy and to provide useful information and references for future development of opioid guidelines to identify adequately supported practice points and areas in need of further scientific evidence.Seven guidelines were identified as pertaining specifically to the long-term use of opioids for general chronic non-cancer pain from an initial search of the PubMed/Medline and Cochrane databases using combinations of the search terms "opioid," "chronic opioid therapy," "chronic pain," "chronic non-cancer pain," "chronic non-malignant pain," "guidelines," "practice guidelines," and "clinical practice guidelines," filtered to include only articles on humans published in the English language over the past 10 years.All guidelines espouse an individual approach to management, beginning with a comprehensive patient evaluation, with particular focus on eliciting factors that may indicate potential drug misuse and abuse, and a trial of therapy to determine the course of treatment. Goals of treatment should be adequately discussed with and consented to by the patient. Opioids are generally not recommended as first-line therapy but, when used, clinicians should closely monitor patients for loss of response, adverse effects or aberrant behavior, and revise the treatment plan accordingly. Urine drug testing (UDT) may be used as a tool to monitor for aberrant behavior or drug misuse; opioid rotation may be considered when loss of response or adverse effects are a concern, at a starting dose lower than the calculated equianalgesic dose.Information on some African nations, countries in the Middle-East, and Pacific Islands is not available and therefore was not included in this review.There is a growing body of scientific evidence to support opioid use in chronic pain. Future work should focus on continuing to generate good-quality evidence on the long-term benefits of opioid therapy, as well as scientific data to guide drug choice and dosing for specific conditions, populations, and situations.
- Patients with Chronic Pain and Dysphagia (CPD): Unmet Medical Need and Pharmacologic Treatment Options. [JOURNAL ARTICLE]
- Curr Med Res Opin 2014 Sep 22.:1-71.
Abstract Background: For properly selected patients experiencing chronic pain, extended-release opioid formulations may represent an appropriate pain management choice. For the many adults, elderly, and children who have medical conditions that make swallowing solid, oral-dose formulations difficult (dysphagia) or painful (odynophagia), this option may be limited. The combination of chronic pain with dysphagia (CPD) presents a challenge to physicians and patients alike when oral opioid analgesia is needed to control pain, but patients are unable to swallow solid, oral dosage forms. Methods: A Medline search was performed (1990 to 2013) using search terms swallowing difficulties, dysphagia, odynophagia, adults, pediatrics, elderly, chronic pain, pain, and opioids. The following websites were searched: American Dysphagia Network, Dysphagia Research Society, World Health Organization, American Pain Society, International Association for the Study of Pain, American Academy of Pain Medicine, and American Society of Interventional Pain Physicians. Chronic pain guidelines from the following professional organizations were searched: American Pain Society, National Comprehensive Cancer Network, American Society of Interventional Pain Physicians, British Geriatric Society, European Society of Medical Oncology, World Health Organization, and the European Association for Palliative Care. Findings: There is an unmet medical need for greater recognition of dysphagia, awareness of potential problems with medication administration in these patients, recognition of alternative drug formulations that are available for use in CPD, and an appreciation that there are new, solid, oral-dose, opioid formulations in development that can mitigate these issues associated with swallowing difficulty while still providing practical, effective analgesia. Current pharmacologic treatments have limitations; new, prospective opioid formulations in clinical development may offer physicians and patients with CPD effective treatment options while mitigating accidental exposure and abuse liability. Conclusions: The number of patients with CPD may be larger than is currently anticipated by healthcare providers. Physicians should proactively include a discussion of dysphagia as part of the patient examination. CPD is an unmet medical need. There are novel opioid formulations in clinical development that address the limitations of current opioid treatments. This manuscript reviews the problems associated with dysphagia on medication administration and adherence, currently available treatment options, and opioid analgesic formulations currently in clinical development.
- Assessing Abuse Potential of New Analgesic Medications Following Market Release: An Evaluation of Internet Discussion of Tapentadol Abuse. [JOURNAL ARTICLE]
- Pain Med 2014 Sep 22.
Research on substance abusers in treatment suggests that tapentadol, a prescription analgesic, may have relatively low abuse potential. Messages posted by recreational drug abusers on online forums were examined for amount of discussion and endorsement for abuse of tapentadol and comparator drugs.Internet messages posted between January 1, 2011 and September 30, 2012 on seven drug-abuse web forums were evaluated. Proportions of posts and unique authors discussing tapentadol were compared with eight comparator compounds. Postcontent was coded to compare endorsement for abuse of tapentadol with two comparators, one drug with high desirability for abuse and one with low desirability for abuse.A total of 1,940,121 messages posted during the study period were copied from selected web forums. The proportion of all posts discussing tapentadol (proportion = 0.0003) was significantly lower than any of the comparator compounds (range of odds ratios from 16.6 to 104.3; P < 0.001). The proportion of unique authors was also lower. Posts coded for endorsement (N = 2,117) yielded an endorsement ratio (Ero) of 2.14 for tapentadol, which was significantly lower than the highly desirable for abuse oxymorphone (ERo = 5.08; P = 0.0011) and was as low as tramadol (ERo = 1.66), which has a long-established profile of low abuse and desirability for abuse.Recreational abusers posting on web forums appear to be less interested in abusing tapentadol when compared with other, selected prescription analgesics based on the amount of discussion (i.e., fewer posts and authors mentioning tapentadol). Endorsement of the product for abuse was also low.
- Tapentadol Abuse Potential: A Postmarketing Evaluation Using a Sample of Individuals Evaluated for Substance Abuse Treatment. [JOURNAL ARTICLE]
- Pain Med 2014 Sep 22.
Abuse of prescription opioid pain relievers continues to be a serious public health concern. In contrast to opioids such as oxycodone or morphine, tapentadol, a prescription analgesic, has two mechanisms of action: μ-opioid receptor agonism and norepinephrine reuptake inhibition. As a result of differences in its receptor pharmacology, there may be differences in its abuse profile. As an initial step toward testing this hypothesis, we present a postmarketing examination of tapentadol's abuse liability relative to comparators.A sentinel sample of 113,914 individuals assessed for substance abuse treatment as part of the NAVIPPRO ASI-MV(®) surveillance system at 624 facilities in 38 states from January 2011 to September 2012 was examined for prevalence and prescription-adjusted prevalence of past 30-day abuse of tapentadol as a compound and its immediate-release (IR) and extended-release (ER) formulations with oxymorphone, hydromorphone, hydrocodone, morphine, fentanyl, oxycodone, tramadol, and buprenorphine as comparators.Tapentadol abuse was reported significantly less often (P < 0.001) than all comparator compounds. Tapentadol IR abuse prevalence was significantly lower than all comparators except fentanyl IR, which had the next lowest unadjusted abuse prevalence. Prevalence of tapentadol ER abuse was lower than comparators except hydromorphone ER. Low prescription-adjusted estimates were observed for tapentadol as a compound as well as its IR and ER formulations, which were among the lowest observed and the lowest of the Schedule II comparators. Prescription-adjusted risk for tapentadol ER was less than comparators except hydromorphone ER (P = 0.06).Tapentadol abuse was seen infrequently in this study and, on a prescription basis, was less likely to be abused than most of the examined Schedule II analgesics.
- Activation of adult rat CNS endothelial cells by opioid-induced toll-like receptor 4 (TLR4) signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae. [JOURNAL ARTICLE]
- Neuroscience 2014 Sep 18.
CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioid-induced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (-)-morphine or its mu opioid receptor (MOR)-inactive metabolite morphine-3-glucuronide (M3G), both known TLR4 agonists. We demonstrate that adult rat CNS endothelial cells express functional TLR4. M3G activated nuclear factor kappaB (NF-κB), increased tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) mRNAs, and released prostaglandin E2 (PGE2) from these cells. (-)-Morphine-induced upregulation of TNFα mRNA and PGE2 release were unmasked by pre-treatment with nalmefene, a MOR antagonist without TLR4 activity (unlike CTAP, shown to have both MOR- and TLR4-activity), suggestive of an interplay between MOR and TLR4 co-activation by (-)-morphine. In support, MOR-dependent Protein Kinase A (PKA) opposed TLR4 signaling, as PKA inhibition (H-89) also unmasked (-)-morphine-induced TNFα and COX2 mRNA upregulation. Intrathecal injection of CNS endothelial cells, stimulated in vitro with M3G, produced TLR4-dependent tactile allodynia. Further, cortical suffusion with M3G in vivo induced TLR4-dependent vasodilation. Finally, endothelial cell TLR4 activation by lipopolysaccharide and/or M3G was blocked by the glial inhibitors AV1013 and propentofylline, demonstrating endothelial cells as a new target of such drugs. These data indicate that (-)-morphine and M3G can activate CNS endothelial cells via TLR4, inducing proinflammatory, biochemical, morphological, and behavioral sequelae. CNS endothelial cells may have previously unanticipated roles in opioid-induced effects, in phenomena blocked by presumptive glial inhibitors, as well as TLR4-mediated phenomena more broadly.