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low dosage naltrexone

Omer Ibrahim, Sara R Hogan, Alok Vij, Anthony P Fernandez
Importance: Familial benign pemphigus, or Hailey-Hailey disease (HHD), is a rare and debilitating genetic dermatosis characterized by chronic, recurrent vesicles, erosions, and maceration in flexural areas. Despite the reported therapeutic modalities, such as topical and systemic corticosteroids, systemic immunomodulators, topical and systemic retinoids, and laser, HHD can still be markedly difficult to control. Objective: To assess low-dose naltrexone hydrochloride in the treatment of recalcitrant HHD...
October 1, 2017: JAMA Dermatology
Rachel Cant, Angus G Dalgleish, Rachel L Allen
The opioid antagonist naltrexone hydrochloride has been suggested to be a potential therapy at low dosage for multiple inflammatory conditions and cancers. Little is known about the immune-modulating effects of naltrexone, but an effect on the activity of toll-like receptor 4 (TLR4) has been reported. We analyzed the effects of naltrexone hydrochloride on IL-6 secretion by peripheral blood mononuclear cells (PBMC) in vitro following stimulation with ligands for TLR4 and for the intracellular receptors TLR7, TLR8, and TLR9...
2017: Frontiers in Immunology
Stephen A Bai, Qinfang Xiang, Andrew Finn
PURPOSE: Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. METHODS: Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded...
February 2016: Clinical Therapeutics
Leslie A Hammer, Hanspeter Waldner, Ian S Zagon, Patricia J McLaughlin
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating myelin-reactive T lymphocytes and demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is the animal model widely utilized to study MS. EAE is mediated by CD4(+) T cells and can be induced in EAE-susceptible mice through immunization with a myelin antigen, such as proteolipid protein 139-151 (PLP139-151) in SJL mice. In this PLP-induced EAE model, autoreactive CD4(+) T cells migrate from peripheral tissues into the CNS where they are reactivated resulting in CNS damage...
January 2016: Experimental Biology and Medicine
Patricia J McLaughlin, Ian S Zagon
Historically, studies on endogenous and exogenous opioids and their receptors focused on the mediation of pain, with excess opiate consumption leading to addiction. Opioid antagonists such as naloxone and naltrexone blocked these interactions, and still are widely used to reverse drug and alcohol overdose. Although specific opioid antagonists have been designed for mu, delta, and kappa opioid receptors, the general antagonists remain the most effective. With the discovery of the opioid growth factor (OGF)-OGF receptor (OGFr) axis as a novel biological pathway involved in homeostasis of replicating cells and tissues, the role of opioid receptor antagonists was expanded...
October 1, 2015: Biochemical Pharmacology
Greg L Plosker
Acamprosate (Campral(®), Aotal(®), Regtect(®)) is one of a limited number of pharmacological treatment options approved as an adjunct to psychosocial interventions to facilitate the maintenance of abstinence in alcohol-dependent patients. It has been used in Europe, the USA and other countries for many years and was recently approved for this indication in Japan. In several randomized, double-blind, placebo-controlled trials (without active comparators), acamprosate in conjunction with psychosocial therapy for 3-12 months was generally significantly better than placebo plus psychosocial interventions in improving various key outcomes, including the proportion of patients who maintained complete abstinence from alcohol (complete abstinence rate), the mean cumulative abstinence duration, the percentage of alcohol-free days and the median time to first drink...
July 2015: Drugs
Patricia J McLaughlin, Daniel P McHugh, Marcus J Magister, Ian S Zagon
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is induced by immunization of mice with myelin oligodendrocytic glycoprotein (MOG35-55) injections, and after 9 days, mice develop behavioral signs of chronic progressive EAE. Proliferation of T and B cells located in peripheral lymph tissues such as spleen and inguinal lymph nodes of C57BL/6J mice are stimulated. The opioid growth factor-opioid growth factor receptor (OGF-OGFr) axis has been shown to effectively limit progression of chronic EAE when mice are treated at the time of induction or at time of established disease...
2015: BMC Immunology
Sunil Deshpande, Daniel E Rivera, Jarred W Younger, Naresh N Nandola
The term adaptive intervention has been used in behavioral medicine to describe operationalized and individually tailored strategies for prevention and treatment of chronic, relapsing disorders. Control systems engineering offers an attractive means for designing and implementing adaptive behavioral interventions that feature intensive measurement and frequent decision-making over time. This is illustrated in this paper for the case of a low-dose naltrexone treatment intervention for fibromyalgia. System identification methods from engineering are used to estimate dynamical models from daily diary reports completed by participants...
September 2014: Translational Behavioral Medicine
Jarred Younger, Luke Parkitny, David McLain
Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated...
April 2014: Clinical Rheumatology
Gillian M Keating
A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients...
January 2014: Clinical Drug Investigation
Elham Khodaverdi, Farnaz Sadat Mirzazadeh Tekie, Farzin Hadizadeh, Haydar Esmaeel, Seyed Ahmad Mohajeri, Sayyed A Sajadi Tabassi, Gholamhossein Zohuri
Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEGPLGA and α-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties...
February 2014: AAPS PharmSciTech
Wang Xuyi, Wang Juelu, Xiang Xiaojun, Li Haiyan, Liu Zheyuan, Gong Zhehui, Dong Guoming, Liu Gang, Li Jin, Hao Wei
BACKGROUND AND OBJECTIVES: We tested long-acting injectable depot naltrexone for its tolerability, pharmacokinetics, and safety in Phase I. METHODS: The Phase I trial enrolled 36 healthy participants in two panels (A, B). In Panel A, 24 subjects were randomly assigned to the high-dosage group (400 mg naltrexone, n=6; placebo, n=6) or low-dosage group (200 mg naltrexone, n=6; placebo, n=6). In Panel B, 12 subjects were randomized to take six doses of monthly injectable naltrexone (400 mg) or placebo...
March 2014: American Journal on Addictions
Ian S Zagon, Renee Donahue, Patricia J McLaughlin
The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a biological pathway that is present in human ovarian cancer cells and tissues. OGF, chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that interfaces with OGFr to delay cells moving through the cell cycle by upregulation of cyclin-dependent inhibitory kinase pathways. OGF inhibitory activity is dose dependent, receptor mediated, reversible, protein and RNA dependent, but not related to apoptosis or necrosis. The OGF-OGFr axis can be targeted for treatment of human ovarian cancer by (i) administration of exogenous OGF, (ii) genetic manipulation to over-express OGFr and (iii) use of low dosages of naltrexone, an opioid antagonist, which stimulates production of OGF and OGFr for subsequent interaction following blockade of the receptor...
May 2013: Experimental Biology and Medicine
Maria A Sullivan, Adam Bisaga, John J Mariani, Andrew Glass, Frances R Levin, Sandra D Comer, Edward V Nunes
BACKGROUND: FDA approval of long-acting injectable naltrexone (Vivitrol) for opioid dependence highlights the relevance of understanding mechanisms of antagonist treatment. Principles of learning suggest an antagonist works through extinguishing drug-seeking behavior, as episodes of drug use ("testing the blockade") fail to produce reinforcement. We hypothesized that opiate use would moderate the effect of naltrexone, specifically, that opiate-positive urines precede dropout in the placebo group, but not in the active-medication groups...
November 1, 2013: Drug and Alcohol Dependence
Jarred Younger, Noorulain Noor, Rebecca McCue, Sean Mackey
OBJECTIVE: To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue. METHODS: Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study...
February 2013: Arthritis and Rheumatism
Sunmee Wee, Leandro F Vendruscolo, Kaushik K Misra, Joel E Schlosburg, George F Koob
Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence...
August 8, 2012: Science Translational Medicine
Patricia J McLaughlin, Ian S Zagon
The opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G(1)/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF...
September 15, 2012: Biochemical Pharmacology
Renee N Donahue, Patricia J McLaughlin, Ian S Zagon
Ovarian cancer is the leading cause of death from gynecological malignancies. Although initial therapeutic modalities are successful, 65% of these women relapse with only palliative treatments available thereafter. Endogenous opioids repress the proliferation of human ovarian cancer cells in vitro, and do so in a receptor-mediated manner. The present study examined whether modulation of opioid systems by the opioid antagonist naltrexone (NTX), alone or in combination with standard of care therapies (taxol/paclitaxel, cisplatin), alters human ovarian cancer cell proliferation in tissue culture and tumor progression in mice...
July 2011: Experimental Biology and Medicine
Guttorm Raknes, Trude Giverhaug
No abstract text is available yet for this article.
May 6, 2011: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
Renee N Donahue, Patricia J McLaughlin, Ian S Zagon
OBJECTIVE: The opioid growth factor (OGF) and its receptor, OGFr, serve as a tonically active inhibitory axis regulating cell proliferation in normal cells and a variety of cancers, including human ovarian cancer. Blockade of OGF and OGFr with the nonselective opioid receptor antagonist naltrexone (NTX) upregulates expression of OGF and OGFr. Administration of a low dosage of NTX (LDN) blocks endogenous opioids from opioid receptors for a short period of time (4-6 h) each day, providing a window of 18-20 h for the upregulated opioids and receptors to interact...
August 2011: Gynecologic Oncology
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