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J Addict Med 2022 Feb 14. Epub 2022 Feb 14.

Psychiatry Residency Spokane, Providence Sacred Heart Medical Center, Spokane, WA, USA (HDB, AGB); College of Osteopathic Medicine, Pacific Northwest University of Health Sciences, Yakima, WA, USA (MMM); Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University Spokane, WA, USA (MFP); Providence Medical Research Center, Providence Health Care, Spokane, WA, USA (EJC).

The botanical product kratom produces opioid-like effects at high doses and is sometimes used for opioid replacement by individuals with opioid use disorder. Mitragynine, a major alkaloid contained in kratom leaves, has been shown to inhibit multiple cytochromes P450 (CYPs) in vitro, including CYP2D6 and CYP3A. As such, kratom may precipitate pharmacokinetic drug interactions when co-consumed with certain medications. Read More

JAMA Pediatr 2022 Mar;176(3):304-311

British Columbia Centre on Substance Use, Vancouver, British Columbia, Canada.

Importance: The ongoing overdose crisis continues to adversely affect adolescents and young adults (AYAs) and has led to numerous preventable deaths. Medications for opioid use disorder (MOUD), such as methadone, buprenorphine, and naltrexone, have the potential to reduce opioid use and associated harms; however, there are concerns that AYAs lack access to these potentially life-saving medications.

Objective: To systematically review peer-reviewed literature on MOUD access and associated factors to synthesize strategies that can improve MOUD access for AYAs who use opioids. Read More

Biochem Pharmacol 2022 01 19;195:114805. Epub 2021 Oct 19.

Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Center for Biomarker Research & Precision Medicine, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.

Opioid-related fatalities involving synthetic opioids have reached unprecedented levels. This study evaluated the respiratory depressant effects of seven fentanyl analogs that have either emerged in the illicit drug supply or been identified in toxicological analyses following fatal or non-fatal intoxications. Adult male Swiss Webster mice were administered fentanyl analogs (isobutyrylfentanyl, crotonylfentanyl, para-methoxyfentanyl, para-methoxybutyrylfentanyl, 3-furanylfentanyl, thiophenefentanyl, and benzodioxolefentanyl) and their effects on minute volume as compared to mu-opioid receptor (MOR) agonist standards (fentanyl, morphine, and buprenorphine) were measured using whole body plethysmography (WBP). Read More

Emerg Med Clin North Am 2021 Aug 9;39(3):677-687. Epub 2021 Jun 9.

Department of Emergency Medicine, Arizona State University, College of Health Solutions, Valleywise Health, 2601 East Roosevelt, Phoenix, AZ 85006, USA.

In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Read More

ACS Chem Neurosci 2021 01 23;12(1):184-194. Epub 2020 Dec 23.

Molecular Modeling and Biopharmaceutical Center and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536, United States.

Opioid drug use, especially heroin, is known as a growing national crisis in America. Heroin itself is a prodrug and is converted to the most active metabolite 6-monoacetylmorphine (6-MAM) responsible for the acute toxicity of heroin and then to a relatively less-active metabolite morphine responsible for the long-term toxicity of heroin. Monoclonal antibodies (mAbs) are recognized as a potentially promising therapeutic approach in the treatment of opioid use disorders (OUDs). Read More

J Pharmacol Exp Ther 2020 12 26;375(3):469-477. Epub 2020 Sep 26.

Departments of Pharmacology (C.B., A.H.K., A.K., M.P.), Veterinary Population Medicine (C.B.), and Psychiatry and Behavioral Sciences (A.H.K.), University of Minnesota Medical School, Minneapolis, Minnesota; Reno School of Medicine, University of Nevada, Reno, Nevada (D.E.R., S.G.P., D.A.); Allegheny Health Network, Pittsburgh, Pennsylvania (S.A.); and Center for Immunology, University of Minnesota, Minneapolis, Minnesota (M.P.)

Monoclonal antibodies (mAbs) and vaccines have been proposed as medical countermeasures to treat opioid use disorder (OUD) and prevent opioid overdose. In contrast to current pharmacotherapies (e.g. Read More

Aust J Gen Pract 2020 06;49(6):339-343

BSc (Hons), MBChB, PhD, FRANZCP, FAChAM, Director, Turning Point, Eastern Health, Vic; Professor of Addiction Studies, Monash University, Vic.

Background: Opioids are frequently used to manage chronic non-cancer pain despite the lack of evidence of benefit and clear evidence of opioid-related harms. Patients undergoing high-dose opioid therapy are at risk of multiple complications, such as opioid toxicity, including fatal overdose and opioid dependence.

Objective: This article provides an overview of the pharmacology of buprenorphine and reviews current evidence for the use of high-dose sublingual buprenorphine-naloxone in the pharmacological management of patients at high risk of complications from chronic opioid use. Read More

J Pharm Biomed Anal 2020 Feb 16;180:113042. Epub 2019 Dec 16.

Inserm, U1144, Paris, France; Paris-Descartes University, UMR-S 1144, Paris, France; Paris-Diderot University, UMR-S 1144, Paris, France; Forensic Toxicology Unit, Forensic Sciences Institute of the French Gendarmerie, Pontoise, France.

Buprenorphine and buprenorphine/naloxone combination are maintenance treatments used worldwide. However, since their marketing, despite ceiling respiratory effects, poisonings and fatalities have been attributed to buprenorphine misuse and overdose. Therefore, to better understand the mechanisms of buprenorphine-related toxicity in vivo, experimental investigations have been conducted, mainly in the rat. Read More

Am J Emerg Med 2020 03 16;38(3):691.e3-691.e4. Epub 2019 Nov 16.

Cook County Health, Department of Emergency Medicine, Division of Medical Toxicology, Chicago, IL, United States.

Naloxone is a frequently utilized and effective treatment to reverse the life-threatening effects of illicit opioid intoxication. Excessive naloxone dosing in these circumstances, however, may lead to naloxone-precipitated opioid withdrawal in individuals with opioid dependence. Buprenorphine, a partial mu-opioid agonist, is increasingly utilized in the Emergency Department (ED) for the treatment of opioid withdrawal syndrome but little is known regarding its utility in cases of naloxone-precipitated opioid withdrawal. Read More

Sci Adv 2019 10 2;5(10):eaax9140. Epub 2019 Oct 2.

Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY, USA.

Opioid use disorders (OUDs) are diseases of the brain with behavioral, psychological, neurobiological, and medical manifestations. Vulnerability to OUDs can be affected by factors such as genetic background, environment, stress, and prolonged exposure to μ-opioid agonists for analgesia. Two standard-of-care maintenance medications, methadone and buprenorphine-naloxone, have a long-term positive influence on health of persons with opioid addiction. Read More

Can Fam Physician 2017 Mar;63(3):200-205

Staff physician in the Department of Family and Community Medicine at St Michael's Hospital in Toronto.

Objective: To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance.

Sources Of Information: PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included. Read More

Subst Abus 2017 Jan-Mar;38(1):18-21. Epub 2016 Dec 7.

a Department of Addiction Psychiatry , University of California San Francisco , San Francisco , California , USA.

Background: Opioid overdose is a growing concern in the United States and internationally. Prehospital or pre-medical personnel (layperson) administration of naloxone, an opioid antagonist, to reverse overdose, is an expanding mode of harm reduction. Recently, community clinics, methadone clinics, needle exchanges, some pharmacies, and other health care facilities have made naloxone available to the community. Read More

Toxicol Sci 2017 02 1;155(2):389-399. Epub 2016 Nov 1.

Inserm, U1144, Paris, France;

Respiratory depression and fatalities have been attributed to ethanol/buprenorphine (BUP) combination in drug addicts maintained with BUP/naloxone or BUP alone. The exact mechanisms of the ethanol/BUP interaction and the contribution to the toxicity of norbuprenorphine (NBUP), the main BUP metabolite with respiratory depressant properties are unknown. We investigated the sedative and plethsymographic effects resulting from the co-administration of intragastric ethanol (3 g/kg) and intravenous BUP (30 mg/kg) in Sprague-Dawley rats. Read More

MMWR Morb Mortal Wkly Rep 2016 Oct 21;65(41):1148-1149. Epub 2016 Oct 21.

Expanding access to office-based medication-assisted treatment with buprenorphine/naloxone for opioid dependence is a key part of the national strategy to address the opioid abuse epidemic (1). However, as buprenorphine/naloxone prescribing increased, emergency department (ED) visits and hospitalizations for unsupervised ingestions by young children began to increase, with buprenorphine/naloxone ingestions becoming the most common cause of hospitalization for medication ingestions by young children during 2010-2011 (2). Buprenorphine ingestions might be asymptomatic or can cause drowsiness, vomiting, or respiratory depression, which if untreated can result in death (3). Read More

Clin Toxicol (Phila) 2017 Jan 19;55(1):12-17. Epub 2016 Oct 19.

a Harvard Medical Toxicology Program , Boston Children's Hospital , Boston , MA , USA.

Context: Exploratory buprenorphine ingestions in young children have been associated with clinically significant toxicity. However, detailed data on the clinical presentation and management of these patients are lacking. In an attempt to obtain more comprehensive data, we sought to examine a single center cohort of patients with report of buprenorphine exposure and provide descriptive analysis of rates of respiratory depression, time to respiratory depression, interventions, disposition, and outcomes. Read More

Am J Addict 2015 Aug 3;24(5):388-90. Epub 2015 Jun 3.

Atlanta VA Medical Center, Decatur, Georgia.

Background: This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin.

Methods: The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. Read More

Hosp Pediatr 2015 Mar;5(3):164-6

Palmetto Health Children's Hospital, Division of Pediatric Critical Care, Columbia, South Carolina

Toxicol Lett 2015 Feb 12;232(3):590-4. Epub 2014 Dec 12.

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The method of choice for reversal of opioid-toxicity is administration of naloxone. This treatment can be accompanied by complications including acute lung-injury, myocardial infarction, or withdrawal-syndrome (in dependent-patients). We aimed to evaluate the efficacy of buprenorphine in reversal of opioid-overdose syndrome in dependent-rats. Read More

Am J Addict 2014 Nov-Dec;23(6):563-9. Epub 2014 Sep 22.

Department of Psychiatry, Ludwig Maximilian University, Munich, Germany; Private Hospital Meiringen, Meiringen, Switzerland.

Background: Some case series mention possible liver toxicity in opioid-dependent patients under buprenorphine treatment.

Methods: This 12-month prospective observational follow-up study in opioid-dependent patients under buprenorphine-naloxone treatment assessed outcome and safety issues. At baseline, 337 eligible datasets were available; 181 patients completed the 12-month study. Read More

Drug Alcohol Depend 2014 Sep 19;142:139-45. Epub 2014 Jun 19.

National Institute of Allergy and Infectious Diseases, Division of AIDS, Prevention Sciences Branch, 6700 B Rockledge Drive, Room 5121, Bethesda, MD 20892, United States.

Background: Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX.

Methods: We compared rates of alanine aminotransferase (ALT) elevation≥grade 3 (ALT≥5. Read More

Toxicol Lett 2014 Jul 21;228(2):75-84. Epub 2014 Apr 21.

Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France; Assistance Publique - Hôpitaux de Paris, Hôpital Lariboisière, Réanimation Médicale et Toxicologique, 2 rue Ambroise Paré, 75010 Paris, France. Electronic address:

Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. Read More

Drug Alcohol Depend 2014 May 23;138:118-23. Epub 2014 Feb 23.

Department of Psychiatry, University of Maryland School of Medicine, 22 S. Greene Street Box 349 P-1-H-10, Baltimore, MD 21201, USA.

Background: Polysubstance use is prevalent in individuals using buprenorphine or methadone nonmedically, with benzodiazepines being a common co-ingestant. The objective of this study was to compare the severity of buprenorphine and methadone toxicity with concomitant use of benzodiazepines.

Methods: A retrospective analysis of buprenorphine and methadone cases from November 1, 2002 to December 31, 2010 reported to the American Association of Poison Control Centers' National Poison Data System (NPDS) was conducted. Read More

Am J Addict 2014 Jan-Feb;23(1):34-40. Epub 2013 Jun 10.

Department of Psychiatry, University of California, San Francisco, California.

Background And Objectives: The purpose of this study was to examine the effect of hepatitis C virus (HCV) infection on buprenorphine pharmacokinetics in opioid-dependent, buprenorphine/naloxone-maintained adults.

Methods: A retrospective analysis of buprenorphine pharmacokinetics in HCV seropositive and seronegative buprenorphine/naloxone-maintained individuals (N = 49) was undertaken.

Results: Relative to HCV seronegative subjects, HCV seropositive subjects had higher buprenorphine exposure, as demonstrated by elevated buprenorphine AUC and Cmax values (p = . Read More

J Emerg Med 2013 Aug 11;45(2):199-205. Epub 2013 May 11.

University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

Background: There exists a significant amount of misinformation regarding methadone and buprenorphine, and a belief that toxicity associated with nonmedical use of methadone and nonmedical use of buprenorphine is similar in severity and outcomes.

Objective: The objective of this study is to compare outcomes associated with nonmedical use of methadone vs. nonmedical use of buprenorphine in patients presenting to the Emergency Department (ED) and reported to poison centers. Read More

Curr Drug Abuse Rev 2013 Mar;6(1):63-70

Department of Psychiatry, University of Munich, Germany.

Opioid maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Risk of diversion and toxicity of opioid prescription drugs, including buprenorphine, causes significant concerns. This is particularly the case in the United States, where the number of related emergency visits is increasing, especially in children. Read More

Eur Respir J 2013 Aug 25;42(2):394-403. Epub 2012 Oct 25.

LDS Hospital, Salt Lake City, UT 84143, USA.

Patients using chronic opioids are at risk for exceptionally complex and potentially lethal disorders of breathing during sleep, including central and obstructive apnoeas, hypopnoeas, ataxic breathing and nonapnoeic hypoxaemia. Buprenorphine, a partial μ-opioid agonist with limited respiratory toxicity, is widely used for the treatment of opioid dependency and chronic nonmalignant pain. However, its potential for causing sleep disordered breathing has not been studied. Read More

Mol Neurobiol 2011 Dec 24;44(3):250-68. Epub 2011 Sep 24.

Department of Psychiatry and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA.

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. Read More

J Acquir Immune Defic Syndr 2011 Mar;56 Suppl 1:S62-7

The CORE Center, Chicago, IL, USA.

Background: The safety of buprenorphine/naloxone (bup/nx) in HIV-infected patients has not been established. Prior reports raise concern about hepatotoxicity and interactions with atazanavir.

Methods: We conducted a prospective cohort study of 303 opioid-dependent HIV-infected patients initiating bup/nx treatment. Read More

Pediatr Crit Care Med 2011 Mar;12(2):e102-7

Department of Pediatrics and Pediatric Critical Care, University of Massachusetts Medical School, Worcester, MA, USA. ernest.pedapaticchmc.org

Background: Sublingual buprenorphine is an alternative to methadone for office-based treatment of opioid dependence. Recent reports have examined a growing number of unintentional buprenorphine exposures in children resulting in significant toxicity, even after a single lick or taste of a sublingual tablet. Here, we report a series of unintentional buprenorphine exposures in toddlers over a 2. Read More