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Am J Forensic Med Pathol 2021 Apr 13. Epub 2021 Apr 13.

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 Apr 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 Apr;28(2):144-146

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

J Forensic Leg Med 2021 Apr 26;79:102149. Epub 2021 Feb 26.

Department of Forensic and Legal Medicine, University of Genova, Via De' Toni 12, 16132, Genova, Italy. Electronic address:

Methadone is a synthetic opioid, a pure agonist of the μ receptor. It is used for opioid maintenance therapy in heroin addiction. In recent years, Italian studies of incidence and prevalence have indicated an increase in the illegal sales of methadone and, consequently, an increase in deaths due to acute methadone intoxication as well. Read More

Drug Alcohol Depend 2021 04 13;221:108599. Epub 2021 Feb 13.

Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive (Mail Code 7764), San Antonio, TX, 78229, USA; Addiction Research, Treatment and Training (ARTT) Center of Excellence, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address:

Background: A significant number of deaths caused by opioids involve fentanyl and/or one of its very potent analogs (e.g., carfentanil). Read More

Anal Chem 2021 02 3;93(7):3576-3585. Epub 2021 Feb 3.

Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315 Oslo, Norway.

Liver organoids are emerging tools for precision drug development and toxicity screening. We demonstrate that electromembrane extraction (EME) based on electrophoresis across an oil membrane is suited for segregating selected organoid-derived drug metabolites prior to mass spectrometry (MS)-based measurements. EME allowed drugs and drug metabolites to be separated from cell medium components (albumin, etc. Read More

Am J Emerg Med 2021 02 7;40:103-105. Epub 2020 Dec 7.

Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU Grossman School of Medicine, 455 1(st) Ave, Rm 124, New York, NY 10016, USA; Department of Health and Mental Hygiene, New York City Poison Control Center, 455 1(st) Ave, Rm 124, New York, NY, 10016, USA.

Background: Illicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly suspected in overdose deaths. However, few prior outbreaks have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without opioid use disorder who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine. 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

Nature 2021 01 9;589(7842):474-479. Epub 2020 Dec 9.

Department of Chemistry, University of California, Davis, Davis, CA, USA.

The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine-like those of other psychedelic compounds-are long-lasting, which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling. Read More

Ther Drug Monit 2021 04;43(2):221-228

NMS Labs, Horsham, Pennsylvania.

Abstract: Discovered in the 1960s, the common anthelminthic levamisole has seen widespread use in veterinary applications. Its use rapidly expanded thereafter to include human medical treatments for a variety of acute and chronic disorders. Because of reports of severe adverse effects, the US Food and Drug Administration withdrew levamisole's approval for human use in 2000; however, medical options outside the United States and illicit options worldwide allow continued accessibility to levamisole. Read More

Med Sci Law 2021 Apr 25;61(2):122-129. Epub 2020 Nov 25.

Forensic Toxicology Service, University Hospitals of Leicester NHS Trust, UK.

Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. To date, there are limited data in the literature to allow for the interpretation of blood concentrations of etizolam in post-mortem cases. A liquid chromatography with tandem mass spectrometry method was used to quantitate etizolam concentrations in 28 post-mortem cases where etizolam was detected. Read More

J Med Chem 2020 12 20;63(23):14647-14667. Epub 2020 Nov 20.

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, United States.

The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Read More

Int J Drug Policy 2020 Oct 8:102976. Epub 2020 Oct 8.

HIV Legal Network, 1240 Bay Street, Suite 600, Toronto, Ontario M5R 2A7 Canada.

The dramatic increase in overdose mortality in North America since 2000 and spikes in harmful drug use in other parts of the world in recent decades challenge drug policy-makers to broaden their definition of harm reduction. Ensuring access to a safe supply of drugs for those obtaining adulterated drugs from illegal markets must be an essential element of preventing overdose and reducing the harms of overdose. Safe supply initiatives, including but not limited to the provision of legally regulated medical-grade heroin or hydromorphone in humane and non-stigmatizing ways, are well justified by the state obligations to protect the right to life and the right to health. 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

BMC Emerg Med 2020 09 5;20(1):71. Epub 2020 Sep 5.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

Background: Amidst the ongoing opioid crisis there are debates regarding the optimal route of administration and dosages of naloxone. This applies both for lay people administration and emergency medical services, and in the development of new naloxone products. We examined the characteristics of naloxone administration, including predictors of dosages and multiple doses during patient treatment by emergency medical service staff in order to enlighten this debate. Read More

ACS Chem Neurosci 2020 Sep 17. Epub 2020 Sep 17.

Department of Forensic Science, College of Humanities and Sciences, Virginia Commonwealth University 1015 Floyd Avenue, Richmond, Virginia 23284, United States.

Krokodil is the street name for a homemade mixture that has been used as a cheap substitute for heroin. The main active substance in krokodil is desomorphine, an opioid that is 10 times more potent than morphine. Krokodil use began in Russia and Ukraine but has spread throughout several countries in Europe and North America. Read More

PeerJ 2020 17;8:e9461. Epub 2020 Jul 17.

Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

Background: Substitution can be defined as the consciously motivated choice to use one drug, either licit or illicit, instead of another, due to perceptions of cost, availability, safety, legality, substance characteristics, and substance attributions. Substitution represents a potential risk to drug users, mainly when substitutes are of higher potency and toxicity. This study offers a basic conceptualization of illicit substitution behavior and describes substitution patterns among users of two highly prevalent drugs of abuse-heroin and cannabis. Read More

J Anal Toxicol 2020 Dec;44(8):927-935

Department of Chemistry and Drugs, National Institute of Toxicology and Forensic Sciences, Las Rozas de Madrid, Madrid 28232, Spain.

Here we report the identification and quantitation of cyclopropyl-fentanyl in a fatality casework occurred due to a poly-drug toxicity in Spain in December 2017. The cyclopropyl-fentanyl was identified in non-biological (paraphernalia) and biological samples (whole-blood, vitreous humor and urine). Conventional techniques (GC-MS) and the UV-Vis spectral allowed differencing between the two structural isomer compounds of fentanyl (cyclopropyl and crotonyl) when the CRM was not available at the laboratory. Read More

J Psychopharmacol 2020 09 17;34(9):999-1007. Epub 2020 Jul 17.

Department of Psychological Sciences, University of Liverpool, UK.

Background: Data on actual harm of magic mushrooms suggest that toxicity and abuse potential is low, however, their legal status suggests otherwise. We aimed to gauge perception of harm of magic mushrooms in both users and mushroom-naïve participants. We also aimed to observe differences in expectations of effects between users and mushroom-naïve participants, and whether motivations for use predicted their expected effects. Read More

World J Psychiatry 2020 May 19;10(5):95-100. Epub 2020 May 19.

Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris-Diderot University, INSERM UMRS-1144, Paris 75010, France.

Lead may contaminate opium, heroin and illicit opiates and is particularly observed in Iran. Lead, a natural heavy metal is able to interfere with several organ functions after ingestion or inhalation. Lead poisoning manifestations are non-specific and thus lead poisoning remains difficult to diagnose. Read More

Cureus 2020 Jan 23;12(1):e6750. Epub 2020 Jan 23.

Public Health Directorate, Cambridgeshire County Council, Cambridge, GBR.

Background:  Drug-related deaths are a growing public health problem in the United Kingdom, overtaking road fatalities and homicides in terms of annual deaths. In this study, we investigated the causes and circumstances of unintentional drug-related deaths occurring in the county of Cambridgeshire, with the objective of identifying the prevalence of physical, mental, and social health problems within this cohort.

Methods:  We collected data on the demographics and mental and physical health of, and drugs contributing to, 30 consecutive unintentional drug-related deaths recorded by the Cambridgeshire and Peterborough County Council Coroners in 2017. Read More

Int J Drug Policy 2020 03 4;77:102672. Epub 2020 Feb 4.

Health Protection Research Unit for Chemical and Radiation Threats and Hazards, Newcastle University, Newcastle NE2 4HH, United Kingdom.

Background: There have been recent increases in use of new psychoactive substances (NPS) associated with acute health harms including hospital presentations due to toxicity and increasing numbers of deaths. In response, the UK Government enacted generic legislation on 26th May 2016 (the Psychoactive Substances Act) making it an offence to produce, possess with intent to supply, supply, import or export, or possess within a custodial setting a psychoactive substance. We studied the impact of this Act on monthly frequency of enquiries made by health professionals to the UK National Poisons Information Service (NPIS) about NPS. Read More

Hum Exp Toxicol 2020 Jun 3;39(6):808-815. Epub 2020 Feb 3.

Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Context: Heavy metals, including thallium and lead, are introduced to illicit drug users' body as a result of using drugs such as cocaine and heroin.

Objective: This study aimed to determine urine, blood, and hair thallium (Tl) concentrations in illicit opioid users along with the relevant clinical signs and symptoms consistent with thallotoxicosis and to compare them with the corresponding variables in the control non-opioid user group.

Materials And Methods: This case-control study was conducted on 50 illicit opioid users who had abused opioids continuously for more than a year, referred to Amirie Drug Abuse Treatment Clinic in Kashan, Iran. Read More

CJEM 2020 03;22(2):178-186

Department of Emergency Medicine, University of British Columbia, Vancouver, BC, Canada.

Objectives: Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses.

Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old. Read More

Curr Neuropharmacol 2020 ;18(9):809-837

Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, Herts, UK

Background: NPS belonging to the benzodiazepine (BZD) class, e.g., 'legal/designer BZDs'/'research chemicals', have recently emerged in the drug (mainly online/virtual) market. Read More

Front Immunol 2019 20;10:2904. Epub 2019 Dec 20.

Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States.

Research on the effects of opioids on immune responses was stimulated in the 1980s by the intersection of use of intravenous heroin and HIV infection, to determine if opioids were enhancing HIV progression. The majority of experiments administering opioid alkaloids (morphine and heroin) , or adding these drugs to cell cultures , showed that they were immunosuppressive. Immunosuppression was reported as down-regulation: of Natural Killer cell activity; of responses of T and B cells to mitogens; of antibody formation and ; of depression of phagocytic and microbicidal activity of neutrophils and macrophages; of cytokine and chemokine production by macrophages, microglia, and astrocytes; by sensitization to various infections using animal models; and by enhanced replication of HIV . Read More

J Med Internet Res 2020 01 3;22(1):e15645. Epub 2020 Jan 3.

Denver Public Health, Denver Health and Hospital Authority, Denver, CO, United States.

Background: Timely, precise, and localized surveillance of nonfatal events is needed to improve response and prevention of opioid-related problems in an evolving opioid crisis in the United States. Records of naloxone administration found in prehospital emergency medical services (EMS) data have helped estimate opioid overdose incidence, including nonhospital, field-treated cases. However, as naloxone is often used by EMS personnel in unconsciousness of unknown cause, attributing naloxone administration to opioid misuse and heroin use (OM) may misclassify events. Read More