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Ann Emerg Med 2022 Apr 28. Epub 2022 Apr 28.

Clinical Toxicology Research Group, University of Newcastle, Newcastle, Australia.

Study Objective: Large doses of intramuscular (IM) naloxone are commonly used in out-of-hospital settings to reverse opioid toxicity; however, they are used less commonly in hospitals because of concerns about opioid withdrawal, particularly agitation. We aimed to determine the frequency of severe agitation following a single 1.6 mg IM naloxone dose. Read More

Drug Alcohol Depend 2022 04 24;233:109376. Epub 2022 Feb 24.

Centre for Pharmaceutical Medicine Research, Institute of Pharmaceutical Medicine, King's College London, Franklin-Wilkins Building, Stamford Street, London SE1 9NH, UK; National Programme on Substance Abuse Deaths, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK.

Background: Dihydrocodeine (DHC) is considered a 'weak' opioid, but there is evidence of its increasing misuse in overdose deaths. This research aims to analyse trends in DHC-related deaths in England relevant to source and dose of DHC, and decedent demographics.

Methods: Cases from England reported to the National Programme on Substance Abuse Deaths (NPSAD) where DHC was identified at post-mortem and/or implicated in death between 2001 and 2020 were extracted for analysis. Read More

Fa Yi Xue Za Zhi 2021 Dec;37(6):763-775

School of Forensic Medicine, Kunming Medical University, Kunming 650500, China.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. Read More

J Pharmacol Exp Ther 2022 05 13;381(2):129-136. Epub 2022 Feb 13.

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota (C.A.B., M.M.W., M.P.); Department of Veterinary Population Medicine, University of Minnesota, Minneapolis, Minnesota (M.M.W.); Reno School of Medicine, University of Nevada, Reno, Nevada (S.G.P., J.A.-U., D.A.); University of Minnesota Center for Immunology, Minneapolis, Minnesota (M.P.); and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington (M.P.).

The incidence of fatal drug overdoses in the United States is an alarming public health threat that has been exacerbated by the COVID-19 pandemic, resulting in over 100,000 deaths between April 2020 and April 2021. A significant portion of this is attributable to widespread access to fentanyl and other synthetic opioids, alone or in combination with heroin or psychostimulants, such as cocaine or methamphetamine. Monoclonal antibodies (mAb) offer prophylactic and therapeutic interventions against opioid overdose by binding opioids in serum, reducing distribution of drug to the brain and other organs. Read More

Lancet Public Health 2022 03 10;7(3):e210-e218. Epub 2022 Feb 10.

Heller School for Social Policy and Management, Brandeis University, Waltham, MA, USA; Brown University School of Public Health, Providence, RI, USA. Electronic address:

Background: The US overdose crisis is driven by fentanyl, heroin, and prescription opioids. One evidence-based policy response has been to broaden naloxone distribution, but how much naloxone a community would need to reduce the incidence of fatal overdose is unclear. We aimed to estimate state-level US naloxone need in 2017 across three main naloxone access points (community-based programmes, provider prescription, and pharmacy-initiated distribution) and by dominant opioid epidemic type (fentanyl, heroin, and prescription opioid). Read More

Clin Toxicol (Phila) 2022 Jun 4;60(6):694-701. Epub 2022 Feb 4.

Department of Emergency Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Background: Induction of buprenorphine, an evidence-based treatment for opioid use disorder (OUD), has been reported to be difficult for people with heavy use of fentanyl, the most prevalent opioid in many areas of the country. In this population, precipitated opioid withdrawal (POW) may occur even after individuals have completed a period of opioid abstinence prior to induction. Our objective was to study potential associations between fentanyl, buprenorphine induction, and POW, using social media data. Read More

Int J Drug Policy 2022 03 7;101:103574. Epub 2022 Jan 7.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: The drug toxicity crisis continues to be a significant cause of death. Over 24,600 people died from opioid toxicity in Canada over the last 5 years. Safe supply programs are required now more than ever to address the high rate of drug toxicity overdose deaths caused by illicit fentanyl and its analogues. Read More

Neurotoxicol Teratol 2022 Mar-Apr;90:107063. Epub 2022 Jan 7.

The Ross Laboratory for Studies in Neural Birth Defects, Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada, The Hebrew University-Hadassah Medical School, Box 12272, 91120 Jerusalem, Israel; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Neurobehavioral teratology is the study of typically subtle neurobehavioral birth defects. Our previously described mouse model demonstrated septohippocampal cholinergic innervation-related molecular and behavioral deficits after prenatal exposure to heroin. Since the alterations are below malformation level, they are likely to represent consequences of regulatory processes, feasibly gene expression. Read More

J Clin Med 2021 Oct 20;10(21). Epub 2021 Oct 20.

Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles, 34394 Montpellier, France.

Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. Read More

Life Sci 2021 Dec 29;287:120103. Epub 2021 Oct 29.

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 232 Outer Ring Road, University Town, Guangzhou 510006, China; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, China. Electronic address:

Background: Heroin is a semi-synthetic opioid that is commonly abused drugs in the world. It can cause hepatic injury and lead to multiple organs dysfunction to its addicts. Only a few reports exist on the metabolic changes and mechanisms in the liver of heroin-addicted mice with hepatic injury. Read More

Drug Alcohol Depend 2021 12 30;229(Pt B):109112. Epub 2021 Sep 30.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia; School of Psychology, University of Tasmania, Hobart, Australia.

Background: Identifying differences in unintentional versus intentional drug poisoning deaths can inform targeted prevention. This study aimed to: compare unintentional versus intentional drug poisoning deaths by drug involvement, age and sex; describe patterns of drug involvement by intent; and describe common drug patterns by age and sex.

Methods: Cases comprised deaths among Australians aged ≥15 where drug poisoning was the underlying cause (Cause of Death Unit Record File 2012-2016). Read More

J Anal Toxicol 2021 Sep 30. Epub 2021 Sep 30.

NMS Labs, 200 Welsh Road, Horsham, PA 19044.

Toxic adulterants are drug or chemical agents used to add bulk volume to traditional drugs of abuse such as cocaine, and heroin. These cutting agents include levamisole, metamizole, noxiptillin, phenacetin, and xylazine as well as common legal drugs such as acetaminophen, caffeine, diphenhydramine, lidocaine, quinine, quetiapine, and tramadol. Because they possess pharmacological activity they result in exposure of the user, but also in the case of pregnant women, the developing fetus, to potential drug toxicity. Read More

ACS Chem Neurosci 2021 10 16;12(19):3527-3534. Epub 2021 Sep 16.

Department of Forensic Science, College of Humanities and Sciences, Virginia Commonwealth University, Richmond, Virginia 23284, United States.

Bucinnazine (1-butyryl-4-cinnamylpiperazine) is a synthetic opioid recently discovered in heroin seized samples in the U.S and in Europe. It was first synthesized in the late 1960s and has been used for the treatment of cancer-associated chronic pain in China for many years. Read More

Toxins (Basel) 2021 07 24;13(8). Epub 2021 Jul 24.

Department of Ecology and Evolutionary Biology & UCLA La Kretz Center for California Conservation Science, Institute of the Environment and Sustainability, University of California, Los Angeles, CA 90095, USA.

Tetrodotoxin (TTX) is a potent neurotoxin that was first identified in pufferfish but has since been isolated from an array of taxa that host TTX-producing bacteria. However, determining its origin, ecosystem roles, and biomedical applications has challenged researchers for decades. Recognized as a poison and for its lethal effects on humans when ingested, TTX is primarily a powerful sodium channel inhibitor that targets voltage-gated sodium channels, including six of the nine mammalian isoforms. Read More

J Clin Pharmacol 2021 08;61 Suppl 2:S70-S88

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

Opioids were the most common drug class resulting in overdose deaths in the United States in 2019. Widespread clinical use of prescription opioids for moderate to severe pain contributed to the ongoing opioid epidemic with the subsequent emergence of fentanyl-laced heroin. More potent analogues of fentanyl and structurally diverse opioid receptor agonists such as AH-7921 and MT-45 are fueling an increasingly diverse illicit opioid supply. Read More

Aging (Albany NY) 2021 07 19;13(14):18669-18688. Epub 2021 Jul 19.

NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

Background: Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown.

Methods: A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. Read More

Neuropharmacology 2021 10 13;197:108713. Epub 2021 Jul 13.

Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, Baltimore, MD, 21224, USA. Electronic address:

Alcohol is the most commonly used psychoactive drug, often taken in conjunction with opioid drugs. Since both alcohol and opioids can induce CNS depression, it is often assumed that alcohol potentiates the known hypoxic effects of opioid drugs. To address this supposition, we used oxygen sensors to examine the effects of alcohol on brain oxygenation and hypoxic responses induced by intravenous heroin in awake, freely moving rats. Read More

J Clin Pharm Ther 2021 Dec 8;46(6):1505-1508. Epub 2021 Jul 8.

Neumentum Inc, Summit, NJ, USA.

What Is Known And Objective: A large percentage of opioid overdose fatalities involve fentanyl or one of its legal or illegal analogs (F/FAs). Is there something about the pharmacology of these drugs that make them unusually dangerous in an overdose?

Comment: Some of the reasons for the dangers of overdose of F/FAs is their high potency and low cost (that leads to wide distribution). But it is rarely asked if the basic pharmacology of F/FAs differ in some fundamental way from conventional opioids such as morphine and heroin. Read More

Eur Rev Med Pharmacol Sci 2021 Jun;25(12):4394-4399

School of Law, Camerino University, Camerino (MC), Italy.

Objective: New fentanyl analogues have been constantly emerging into the illegal drug market as cheap substitutes of heroin posing a serious health threat for consumers because of their high toxicity. Analytical methods to disclose the presence of these compounds in biological fluids of intoxicated individuals need to be updated to keep up with the new trends. In this study, we updated an ultra-high-performance liquid chromatography-tandem mass spectrometry method previously developed, for detecting some new fentanyl analogues and metabolites (sufentanil and norsufentanil, cis-3-methylnorfentanyl, trans-3-methylnorfentanyl, metabolites of cis and transmethylfentanyl, beta-phenylfentanyl, phenylfentanyl, para-fluoro furanyl fentanyl, isobutyryl fentanyl and ocfentanil) in urine sample. Read More

J Anal Toxicol 2022 May;46(5):471-478

Toxicology Unit, Imperial College London, Charing Cross Campus, St. Dunstan's Road, London W6 8RP, UK.

Pregabalin (PGL) is a gabapentinoid used to treat epilepsy, neuropathic pain and generalized anxiety disorder. PGL is also misused by heroin users as it enhances the effects of heroin. While it is thought those who misuse PGL take it in amounts greater than the recommended therapeutic dose, it is unknown whether there is a significant difference between the amounts of PGL used by heroin users compared to non-heroin users. Read More

J Clin Pharm Ther 2021 Dec 10;46(6):1501-1504. Epub 2021 Jun 10.

Neumentum Inc, Summit, NJ, USA.

What Is Known And Objective: Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose.

Comment: Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the μ-opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up?

What Is New And Conclusion: As a competitive antagonist at μ-opioid receptors, naloxone is often a life-saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non-opioids. Read More

PLoS One 2021 26;16(5):e0252090. Epub 2021 May 26.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Introduction: Increased use of crystal methamphetamine ("crystal meth") has been observed across North America and international jurisdictions, including a notable increase in the presence of methamphetamines in illicit drug toxicity deaths in British Columbia (BC), Canada. We used data from a cross-sectional survey and urine toxicology screening to report the prevalence, correlates, and validity of self-reported crystal meth use among clients of harm reduction sites in BC.

Materials And Methods: Survey data were collected from 1,107 participants across 25 communities in BC, through the 2018 and 2019 Harm Reduction Client Survey. Read More

Arch Toxicol 2021 08 11;95(8):2627-2642. Epub 2021 May 11.

Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, Sydney, NSW, 2070, Australia.

Opioid-induced respiratory depression is potentially life-threatening and often regarded as the main hazard of opioid use. Main cause of death is cardiorespiratory arrest with hypoxia and hypercapnia. Respiratory depression is mediated by opioid μ receptors expressed on respiratory neurons in the CNS. Read More

Am J Forensic Med Pathol 2021 Sep;42(3):216-224

From the Toxicology Department, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI.

Abstract: Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. Read More

Leg Med (Tokyo) 2021 Jul 7;51:101877. Epub 2021 Apr 7.

Department of Law, Institute of Legal Medicine, University of Macerata, Macerata, Italy.

Heroin-related mortality is a complex phenomenon involving several factors that make an individual more susceptible to opioid toxicity. Among these, pre-existing pathological conditions play an important role. The current paper reviewed 51 autopsied cases performed over the last 30 years, each subject ("frequent heroin user") having taken heroin intravenously alone before death. Read More

Radiol Case Rep 2021 May 20;16(5):1207-1210. Epub 2021 Mar 20.

Division of Neuroradiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

In the midst of the national opioid crisis, it is necessary for emergency physicians and radiologists to be familiar with presentations of opioid-related complications. We describe a case report of a 51-year-old female who developed bilateral cerebellar hemorrhages following opioid and benzodiazepine overdose. Malignant cerebellar edema is a rare but recognized complication following opiate overdose in children or chronic heroin toxicity. Read More

PLoS One 2021 11;16(3):e0246297. Epub 2021 Mar 11.

Department of Clinical Toxicology, Medical University of Gdansk, Gdansk, Poland.

Background: This study was conducted to retrospectively assess the relationships between: rhabdomyolysis (quantified by creatine kinase (CK) activity) and kidney injury (quantified by serum creatinine concentration), sex, age, body temperature on admission, presence of seizures, and agitation or aggression in patients presenting to the Emergency Department with acute recreational drug toxicity. We also investigated the association with the substances ingested.

Methods: All presentations to the 16 sentinel Euro-DEN centres in 10 European countries with acute recreational drug toxicity during the first year of the Euro-DEN study (October 2013 to September 2014) were considered. Read More

Forensic Sci Int 2021 Apr 26;321:110746. Epub 2021 Feb 26.

King Abdul-Aziz Hospital, Laboratory Department, Jeddah, Saudi Arabia. Electronic address:

A more than 500% increase in the number of deaths involving methamphetamine occurred between 2016 and 2018 in Jeddah, Saudi Arabia. As such, this report employed a validated liquid chromatography tandem mass spectrometry method to quantify methamphetamine and its metabolites in bodily fluids from 47 postmortem cases in which methamphetamine was involved. The mean age of the deceased was 33 years old (median: 30, range: 16-63), and 94% were male. Read More

Eur J Emerg Med 2021 04;28(2):144-146

Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners.