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https://www.readbyqxmd.com/read/28345745/in-vitro-and-in-vivo-assessment-of-the-abuse-potential-of-pf614-a-novel-bio-md%C3%A2-prodrug-of-oxycodone
#1
D Lynn Kirkpatrick, William K Schmidt, Ricardo Morales, John Cremin, Julie Seroogy, Craig Husfeld, Thomas Jenkins
OBJECTIVE: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28343650/-surveillance-system-on-drug-abuse-interest-of-the-french-national-oppidum-program-of-french-addictovigilance-network
#2
Elisabeth Frauger, Liselotte Pochard, Quentin Boucherie, Adeline Giocanti, Cécile Chevallier, Amélie Daveluy, Valérie Gibaja, Anne-Sylvie Caous, Céline Eiden, Nicolas Authier, Reynald Le Boisselier, Marylène Guerlais, Émilie Jouanjus, Marion Lepelley, Véronique Pizzoglio, Stéphanie Pain, Nathalie Richard, Joëlle Micallef
It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs...
February 22, 2017: Thérapie
https://www.readbyqxmd.com/read/28341939/the-basic-pharmacology-of-opioids-informs-the-opioid-discourse-about-misuse-and-abuse-a-review
#3
REVIEW
Joseph V Pergolizzi, Jo Ann LeQuang, Garrett K Berger, Robert B Raffa
Morphine and other opioids are widely used to manage moderate to severe acute pain syndromes, such as pain associated with trauma or postoperative pain, and they have been used to manage chronic pain, even chronic nonmalignant pain. However, recent years have seen a renewed recognition of the potential for overuse, misuse, and abuse of opioids. Therefore, prescribing opioids is challenging for healthcare providers in that clinical effectiveness must be balanced against negative outcomes-with the possibility that neither are achieved perfectly...
March 24, 2017: Pain and Therapy
https://www.readbyqxmd.com/read/28340233/increase-in-drug-overdose-deaths-involving-fentanyl-rhode-island-january-2012-march-2014
#4
Melissa C Mercado, Steven A Sumner, M Bridget Spelke, Michele K Bohm, David E Sugerman, Christina Stanley
Objective.:  This study identified sociodemographic, substance use, and multiple opioid prescriber and dispenser risk factors among drug overdose decedents in Rhode Island, in response to an increase in overdose deaths (ODs) involving fentanyl. Methods.:  This cross-sectional investigation comprised all ODs reviewed by Rhode Island's Office of the State Medical Examiners (OSME) during January 2012 to March 2014. Data for 536 decedents were abstracted from OSME's charts, death certificates, toxicology reports, and Prescription Monitoring Program (PMP) databases...
March 6, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28340165/attitudes-toward-opioids-and-risk-of-misuse-abuse-in-patients-with-chronic-noncancer-pain-receiving-long-term-opioid-therapy
#5
Grisell Vargas-Schaffer, Jennifer Cogan
Objectives.:  To determine the attitudes of patients toward long-term opioid therapy (LtOT) and the potential risk of misuse/abuse in patients with chronic noncancer pain (CNCP). Design.:  Prospective, descriptive epidemiological study. Setting.:  Multidisciplinary tertiary care pain center within the Montreal University Health Center. Subjects.:  Patients who had had at least one visit at least one year prior to the invitation...
March 7, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28340145/human-abuse-potential-of-the-new-opioid-analgesic-molecule-nktr-181-compared-with-oxycodone
#6
Lynn Webster, Jack Henningfield, August R Buchhalter, Suresh Siddhanti, Lin Lu, Aleksandrs Odinecs, Carlo J Di Fonzo, Michael A Eldon
Objective.:  Evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of NKTR-181, a novel mu-opioid agonist molecule, relative to oxycodone. Design.:  This randomized, single-center, double-blind, active- and placebo-controlled five-period crossover study enrolled healthy, adult, non-physically dependent recreational opioid users. Setting.:  Inpatient clinical research site. Subjects. : Forty-two randomized subjects (73...
March 10, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28315148/a-case-of-cardiac-tamponade-due-to-an-isolated-abscess-in-the-ascending-aorta-of-a-pregnant-woman-with-a-history-of-intravenous-substance-abuse
#7
Brandy Shattuck, John Livingstone
We describe the case of a 23-year-old white female, 10-12 weeks pregnant, with a history of intravenous drug use and a recently diagnosed pneumonia, who was found deceased in her bed after a night of sleep. Although postmortem serum toxicology tested positive for alprazolam, tetrahydrocannabinol, and morphine, the ultimate cause of death was determined to be cardiac tamponade secondary to an isolated abscess in the ascending aorta. The patient had several risk factors for aortic rupture and cardiac tamponade including intravenous drug use, pneumonia, and pregnancy...
March 17, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28279667/preclinical-assessment-of-the-abuse-potential-of-the-orexin-receptor-antagonist-suvorexant
#8
Stephanie Born, David V Gauvin, Suman Mukherjee, Richard Briscoe
Suvorexant (Belsomra(®)) is a dual orexin receptor antagonist approved for the treatment of insomnia. Because of its pharmacology within the central nervous system, intended therapeutic indication, and first-in-class status, an assessment of suvorexant abuse liability potential was required prior to marketing approval. The nonclinical abuse liability potential studies for suvorexant included: 1) rat drug-dependence model to assess physical dependence following abrupt cessation; 2) rat drug-discrimination model to examine the potential similarity of the interoceptive or subjective effects of suvorexant to those elicited by zolpidem and morphine; 3) self-administration model to assess the relative reinforcing efficacy of suvorexant in rhesus monkeys conditioned to self-administer methohexital...
March 6, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28264976/a-pten-regulated-checkpoint-regulates-surface-delivery-of-delta-opioid-receptors
#9
Daniel J Shiwarski, Alycia Tipton, Melissa D Giraldo, Brigitte F Schmidt, Michael S Gold, Amynah A Pradhan, Manojkumar A Puthenveedu
The delta opioid receptor (δR) is a promising alternate target for pain management, because δR agonists show decreased abuse potential compared to current opioid analgesics that target the mu opioid receptor. A critical limitation in developing δR as an analgesic target, however, is that δR agonists show relatively low efficacy in vivo, requiring the use of high doses that often cause adverse effects such as convulsions. Here we tested whether intracellular retention of δR in sensory neurons contributes to this low δR agonist efficacy in vivo by limiting surface δR expression...
March 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28243713/mper1-promotes-morphine-induced-locomotor-sensitization-and-conditioned-place-preference-via-histone-deacetylase-activity
#10
Stéphanie Perreau-Lenz, Laura-Sophie Hoelters, Sarah Leixner, Carla Sanchis-Segura, Anita Hansson, Ainhoa Bilbao, Rainer Spanagel
RATIONALE: Previous studies have shown that repeated exposure to drugs of abuse is associated with changes in clock genes expression and that mice strains with various mutations in clock genes show alterations in drug-induced behaviors. OBJECTIVE: The objective of this study is to characterize the role of the clock gene mPer1 in the development of morphine-induced behaviors and a possible link to histone deacetylase (HDAC) activity. METHODS: In Per1 (Brdm1) null mutant mice and wild-type (WT) littermates, we examined whether there were any differences in the development of morphine antinociception, tolerance to antinociception, withdrawal, sensitization to locomotion, and conditioned place preference (CPP)...
February 28, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28237050/characterizing-fentanyl-use-in-methadone-maintained-clients
#11
Cynthia L Arfken, Jessica Suchanek, Mark K Greenwald
AIMS: Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. METHODS: A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan...
April 2017: Journal of Substance Abuse Treatment
https://www.readbyqxmd.com/read/28230448/opioid-use-for-pain-management-after-implementation-of-a-medicaid-short-acting-opioid-quantity-limit
#12
Catherine S Riggs, Sarah J Billups, Samantha Flores, Rachana J Patel, Rachel M F Heilmann, Jessica L Milchak
BACKGROUND: The United States is currently experiencing an opioid abuse epidemic. Many policies and programs have been implemented at local, state, and national levels in an attempt to decrease prescription opioid addiction and overdose. On August 1, 2014, Colorado Medicaid implemented a policy change that limited the quantity of short-acting opioids (SAOs) that could be filled through the Medicaid benefit to no more than 4 tablets per day, or 120 tablets in 30 days. OBJECTIVE: To compare mean total daily dose (TDD) of opioids purchased by Kaiser Permanente Colorado (KPCO) Medicaid patients before and after implementation of the Medicaid SAO quantity limit...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28229178/the-consummatory-and-motivational-behaviors-for-natural-rewards-following-long-term-withdrawal-from-morphine-no-anhedonia-but-persistent-maladaptive-behaviors-for-high-value-rewards
#13
Yingying Li, Xigeng Zheng, Na Xu, Yue Zhang, Zhengkui Liu, Yunjing Bai
RATIONALE: The negative affective state, e.g., anhedonia, emerges after abstinence from abused drugs may be linked to the motivational processes of drug craving and relapse. Although anhedonia diminishes over time with drug abstinence, it is not yet rather explicit whether anhedonia exists or not following protracted withdrawal. OBJECTIVES: The behavioral responses to natural rewards were examined after 2 to 3 weeks withdrawal from morphine. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days...
February 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28226332/responsible-safe-and-effective-prescription-of-opioids-for-chronic-non-cancer-pain-american-society-of-interventional-pain-physicians-asipp-guidelines
#14
Laxmaiah Manchikanti, Adam M Kaye, Nebojsa Nick Knezevic, Heath McAnally, Konstantin Slavin, Andrea M Trescot, Susan Blank, Vidyasagar Pampati, Salahadin Abdi, Jay S Grider, Alan D Kaye, Kavita N Manchikanti, Harold Cordner, Christopher G Gharibo, Michael E Harned, Sheri L Albers, Sairam Atluri, Steve M Aydin, Sanjay Bakshi, Robert L Barkin, Ramsin M Benyamin, Mark V Boswell, Ricardo M Buenaventura, Aaron K Calodney, David L Cedeno, Sukdeb Datta, Timothy R Deer, Bert Fellows, Vincent Galan, Vahid Grami, Hans Hansen, Standiford Helm Ii, Rafael Justiz, Dhanalakshmi Koyyalagunta, Yogesh Malla, Annu Navani, Kent H Nouri, Ramarao Pasupuleti, Nalini Sehgal, Sanford M Silverman, Thomas T Simopoulos, Vijay Singh, Daneshvari R Solanki, Peter S Staats, Ricardo Vallejo, Bradley W Wargo, Arthur Watanabe, Joshua A Hirsch
BACKGROUND: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28196306/effects-of-isoflurane-anesthesia-and-intravenous-morphine-self-administration-on-regional-glucose-metabolism-18-f-fdg-pet-of-male-sprague-dawley-rats
#15
Thomas Y Park, Kevin S Nishida, Colin M Wilson, Shalini Jaiswal, Jessica Scott, Andrew R Hoy, Reed G Selwyn, Bernard J Dardzinski, Kwang H Choi
Although certain drugs of abuse are known to disrupt brain glucose metabolism (BGluM), the effects of opiates on BGluM are not well characterized. Moreover, preclinical positron emission tomography (PET) studies anesthetize animals during the scan, which limits clinical applications. We investigated the effects of 1) isoflurane anesthesia and 2) intravenous morphine self-administration (MSA) on BGluM in rats. Jugular vein cannulated adult male Sprague-Dawley rats self-administered either saline (SSA) or morphine (0...
February 14, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28167137/deletion-of-rictor-in-catecholaminergic-neurons-alters-locomotor-activity-and-ingestive-behavior
#16
Sophia Kaska, Rebecca Brunk, Vedrana Bali, Megan Kechner, Michelle S Mazei-Robison
While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS...
February 3, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28162680/-430-bioequivalence-and-food-effect-of-a-novel-abuse-deterrent-ad-extended-release-er-morphine-product-candidate-compared-with-a-currently-available-non-ad-er-morphine-product
#17
J Dayno, J Lawler, G Niebler, K Lindhardt
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28162673/-425-dissolution-studies-in-the-presence-of-alcohol-with-an%C3%A2-abuse-deterrent-extended-release-morphine-product-candidate
#18
T Elhauge, L Kristensen, J Dayno, K Lindhardt
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28162671/-422-pharmacodynamic-effects-from-a-category-3-intranasal-human-abuse-potential-study-of-an-abuse-deterrent-extended-release-morphine-product-candidate-in-nondependent-recreational-opioid-users
#19
L Webster, M Smith, J Lawler, K Lindhardt, J Dayno
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28156467/association-between-tobacco-use-pain-expression-and-maladaptive-coping-among-patients-with-advanced-cancer
#20
Yu Jung Kim, Akhila Sunkepally Reddy, David Hui, Kimberson Cochien Tanco, Diane D Liu, Minjeong Park, Janet L Williams, Cindy L Carmack, Eduardo Bruera
65 Background: Cancer patients who smoke have been reported to have higher pain expression and increased risk for opioid abuse. The purpose of our study is to evaluate the association between tobacco use, symptom expression, and maladaptive coping in advanced cancer patients. METHODS: We prospectively enrolled advanced cancer patients evaluated in an outpatient Supportive Care Center and collected data on patient demographics, cancer diagnosis, morphine equivalent daily dose (MEDD), cigarette smoking status using Behavioral Risk Factor Surveillance System, symptom expression as measured by Edmonton Symptom Assessment Scale, Cut down/Annoyed/Guilty/Eye opener (CAGE alcoholism questionnaire), short form Screener and Opioid Assessment for Patients with Pain (SOAP-SF) survey, and Brief COPE Questionnaire...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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