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The Identification of Drug Abuse

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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (25 November 2022) | Viewed by 2238483

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Prof. Dr. Maria Pieri

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Department of Advanced Biomedical Science, Legal Medicine Section, University of Naples “Federico II”, 80131 Naples, Italy
Interests: forensic toxicology; data acquisition; gender differences; proteomics; post-mortem analysis; drug abuse; psychoactive substances
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Special Issue Information

Dear Colleagues,

Over the last decades, interest in the field of forensic toxicology has continually increased and assumed a leading role, becoming one of the reference sciences for the elucidation of events of judicial importance. The need to reconcile analytical problems (e.g., relating to the qualitative/quantitative analysis of substances of abuse in complex biological matrices) with judicial requirements (i.e., providing data that can be used as documentary evidence in proceedings) makes the discipline unique among all "analytical" sciences. Thus, the availability of validated procedures, the constant monitoring of analytical performance through quality assurance protocols, the availability of certified “in matrix” standards, and the analytical problems underlying the analysis of new psychoactive substances in blood and other biological fluids represent the challenges of modern forensic toxicology. The correct interpretation of analytical data, especially to elucidate the extent of impairment induced by a certain substance, and "old" issues related to the correct interpretation of post-mortem data (given the impossibility of translating the therapeutic ranges defined “in vivo”) represent further areas of research and debate among scientists. Finally, the possibility of interacting with other disciplines (such as proteomics and social sciences) allows for extending the concept of analytical data acquisition/interpretation beyond the classical limits of forensic toxicology (for example, considering the influence of gender when interpreting the effect of a substance).

We are pleased to invite you to contribute to this Special Issue of Toxics on forensic toxicology, which will be focused on problems related to data acquisition/interpretation, with particular emphasis on post-mortem data, new psychoactive substances, strategies for an appropriate impairment judgment, and application of proteomics to forensic toxicology. In this Special Issue, original research articles and reviews are particularly welcomed.

I look forward to receiving your contributions.

Dr. Maria Pieri
Guest Editor

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Keywords

drugs of abuse detection
interpretation of forensic toxicological data
impairment degree definition
post-mortem data
new psychoactive substances
biological matrices
method validation

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Published Papers (14 papers)

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Editorial

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3 pages, 195 KiB

Open AccessEditorial

The Identification of Drug Abuse

by Maria Pieri

Toxics 2023, 11(5), 444; https://doi.org/10.3390/toxics11050444 - 8 May 2023

Viewed by 1394

Abstract

Forensic toxicology has played a central role since its development in defining mechanisms of acute intoxication, often with a lethal outcome [...] Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

Research

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13 pages, 1615 KiB

Open AccessArticle

UPLC-MS/MS Based Identification and Quantification of a Novel Dual Orexin Receptor Antagonist in Plasma Samples by Validated SWGTOX Guidelines

by Muzaffar Iqbal, Abdullah Alshememry, Faisal Imam, Mohd Abul Kalam, Ali Akhtar and Essam A. Ali

Toxics 2023, 11(2), 109; https://doi.org/10.3390/toxics11020109 - 23 Jan 2023

Cited by 7 | Viewed by 1857

Abstract

Lemborexant (LEM) is a novel dual orexin receptor antagonist (DORA), recently approved for the treatment of insomnia. As with other DORAs, LEM has potential of abuse and therefore placed in Schedule IV class by the United States Drug Enforcement Administration (USDEA). In this study, a sensitive and accurate UPLC-MS/MS assay was developed for the quantification of LEM in human plasma sample using losartan as an internal standard (IS). The chromatographic separation was performed by using gradient elution of mobile phase, comprising of 10 mM ammonium acetate and acetonitrile with a flow rate of 0.3 mL/min. An Acquity UPLC BEH C₁₈ (1.7 μm, 2.1 × 50 mm) column was used for separation of LEM and IS by maintaining the oven temperature of 40 °C. The electrospray ionization in positive mode was used for sample ionization. The precursor to product ion transition of 411.12 > 175.09 (qualifier) and 411.1 > 287.14 (quantifier) was used for detection and quantification of LEM, respectively, in multiple reaction monitoring mode. Being a drug of abuse, the assay was validated according to “Scientific Working Group for Toxicology” (SWGTOX) guidelines, including limit of detection (LOD), limit of quantification (LOQ), precision and bias, calibration model, interferences, carry-over effects, matrix effects, and stability parameters. The LOD and LOQ of the assay were 0.35 and 1.0 ng/mL, respectively. The linear range was between 1–300 ng/mL with correlation coefficient of ≥0.995. The method was also cross validated in rat plasma samples with acceptable ranges of precision and accuracy before its application for pharmacokinetic study in rats. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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12 pages, 841 KiB

Open AccessArticle

Atypical Fentanyl Transdermal Patch Consumption and Fatalities: Case Report and Literature Review

by Federico Manetti, Maria Chiara David, Sara Gariglio, Francesca Consalvo, Martina Padovano, Matteo Scopetti, Antonio Grande and Alessandro Santurro

Toxics 2023, 11(1), 46; https://doi.org/10.3390/toxics11010046 - 31 Dec 2022

Cited by 5 | Viewed by 7107

Abstract

Fentanyl is a synthetic L-opioid receptor agonist, approximately 100 times more potent than morphine, that is experiencing an upward trend in the field of abuse. Fentanyl patches’ abusive consumption can occur either by transdermal absorption or through other atypical and ingenious routes. In the present case, a 29-year-old man with a history of illicit drug use was found dead in a suburban neighborhood of an Italian city. At autopsy, lungs appeared increased in weight and showed minute subpleural hemorrhages. Airways contained abundant reddish foamy material; in addition, a fentanyl patch protective film was found inside the left main bronchus. Toxicological analysis revealed the presence of morphine, fentanyl, BEG and ethyl alcohol in peripheric blood; 6-MAM was also revealed in urine. Findings collected during post-mortem investigations allowed us to identify fentanyl consumption as the cause of death. Fentanyl consumption presumably took place by chewing of a transdermal patch, with subsequent aspiration of the protective film. The pathophysiology of death can be identified as combined respiratory failure—both central suppression and a fentanyl-induced increase in muscular stiffness; a further minor contribution may be identified in the mechanical airflow obstruction caused by the presence of the protective film at the bronchial level. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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8 pages, 672 KiB

Open AccessArticle

Helium Suicide, a Rapid and Painless Asphyxia: Toxicological Findings

by Anna Carfora, Raffaella Petrella, Giusy Ambrosio, Pasquale Mascolo, Bruno Liguori, Christian Juhnke, Carlo Pietro Campobasso and Thomas Keller

Toxics 2022, 10(8), 424; https://doi.org/10.3390/toxics10080424 - 28 Jul 2022

Cited by 3 | Viewed by 2183144

Abstract

Suicide by helium inhalation has become increasingly common in the last few decades in Europe and the US because it produces a quick and painless death. Inhaled-gas suicides can easily be assessed through death scene investigation and autopsy. However, helium is a colorless and odorless inert gas that unfortunately cannot be detected using standard toxicological analysis. A successful gas analysis was performed following the suicide of a 17-year-old female. For the detection of helium, central/peripheral blood samples and gaseous samples from the esophagus, stomach, and upper and lower respiratory airways (from the trachea and the primary left and right bronchia) were collected with a gastight syringe, ensuring minimal dilution. Qualitative analyses were positive in all gaseous samples. Quantitative analyses were performed using a special gas-inlet system with a vacuum by which the sample can be transferred to a mass spectrometer, reducing the risk of contamination. Helium concentrations were 20.16% from the trachea, 12.33% from the right lung, and 1.5% from the stomach. Based on the high levels of helium, the cause and manner of death were assessed as asphyxia suicide by inhalation of helium. Therefore, toxicological analyses should always be applied in order to gain evidence of inhaled gas in gaseous samples. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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7 pages, 725 KiB

Open AccessArticle

Carbamazepine Overdose after Psychiatric Conditions: A Case Study for Postmortem Analysis in Human Bone

by Lucia Fernández-López, Rosanna Mancini, Maria-Concetta Rotolo, Javier Navarro-Zaragoza, Juan-Pedro Hernández del Rincón and Maria Falcón

Toxics 2022, 10(6), 322; https://doi.org/10.3390/toxics10060322 - 13 Jun 2022

Cited by 5 | Viewed by 2328

Abstract

Carbamazepine is the main option used as a preventive medication to treat bipolar disorder when there is no response to lithium. Carbamazepine toxicity is defined as serum levels greater than 12 μg/mL, with severe toxicity occurring over 40 μg/mL, reduced to 30 μg/mL when combined with pharmacological treatment, i.e., benzodiazepines or antidepressants. For these reasons, it is necessary to find a validated tool to determine carbamazepine levels in an autopsy to rule out suicide or to know if the death was a consequence of an adverse drug reaction (ADR), especially when only bones can be accessed. We have validated a tool to detect and quantify drug concentration in bone. Our results showed a peak for carbamazepine at minute 12 and a mass fragment of 193 m/z. This case study is the first time in the literature that carbamazepine has been detected and quantified in bone. These results demonstrate that carbamazepine can be detected in bone tissue from forensic cases, but almost more importantly, that the method proposed is valid, reliable, and trustworthy. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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7 pages, 249 KiB

Open AccessArticle

Suicide by Pesticide (Phorate) Ingestion: Case Report and Review of Literature

by Angela Simonelli, Anna Carfora, Pascale Basilicata, Bruno Liguori, Pasquale Mascolo, Fabio Policino, Massimo Niola and Carlo Pietro Campobasso

Toxics 2022, 10(5), 205; https://doi.org/10.3390/toxics10050205 - 21 Apr 2022

Cited by 6 | Viewed by 4749

Abstract

It has been estimated that approximately one in seven of all global suicides is due to pesticide self-poisoning, mostly in rural areas of developing countries. Organophosphorus (OP) compounds are a group of pesticides exerting their toxicological effects through non-reversible inhibition of the enzyme acetylcholinesterase (AChE). Among these compounds, phorate (thimet) is one of the most dangerous compounds, the use of which is restricted in many countries. A case of intentional suicide after phorate ingestion in a 24-year-old Bengali male is described. This is the second case of suicidal ingestion of phorate reported in the forensic literature, and the first presenting complete toxicological findings. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

12 pages, 3262 KiB

Open AccessArticle

Diquat Poisoning: Care Management and Medico-Legal Implications

by Pascale Basilicata, Maria Pieri, Angela Simonelli, Emanuele Capasso, Claudia Casella, Tina Noto, Fabio Policino and Pierpaolo Di Lorenzo

Toxics 2022, 10(4), 166; https://doi.org/10.3390/toxics10040166 - 30 Mar 2022

Cited by 12 | Viewed by 4230

Abstract

Acute chemical intoxication represents one of the major causes of Emergency Room admittance, and possible errors in diagnosis are extremely frequent, especially when patients present generic and non-specific symptoms. Diquat, a bipyridyl class of herbicides, exerts high intrinsic toxicity as a consequence of free oxygen radicals, leading to cellular death and organ dysfunctions. Following ingestion, with the major source of absorption for suicidal purposes, the chemical induces local irritating effects; systemic symptoms appear later, while specific symptoms can occur in the following 48 h. A smoker and hypertensive 50-year-old man arrives at the E.R., reporting that an episode of herbicide inhalation occurred few hours earlier. Physical examination evidenced alkalosis with hypoxemia, leucocytosis, mild hyperglycaemia and moderate increase in creatine kinase and myoglobin. Despite blood creatine kinase and myoglobin values that were higher than normal, he was prescribed with hydration and anti-pain therapy. During the night, the man left the hospital; he returned the next morning at 8:45 a.m., with cardiorespiratory arrest, medium fixed non-reactive mydriasis, diffused cyanosis of the skin and of the mucous membranes, as well as imperceptible pulse and peripheral pressure. Despite resuscitation attempts, the patient died at 9:30 a.m.; the body was immediately transferred to the morgue. Autopsy and toxicological analyses were carried out nine days later, evidencing paraquat ingestion for suicidal purposes. GC/MS analyses to verify the presence of diquat were performed on body fluids and gastric and colon contents; all specimens resulted positive, thus confirming the cause of death as herbicide ingestion (blood diquat concentration of 1.2 mg/L; more than twice the minimum to observe a systemic poisoning). The procedure followed for patient management resulted to be not in line with the provisions of both guidelines and good clinical practices. Staff did not perform clinical-diagnostical monitoring of the patient’s condition or ask for more specific analyses (i.e., serum creatine phosphokinase monitoring). This misconduct led to a decrease in the patient’s chances to survive. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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11 pages, 1278 KiB

Open AccessArticle

Determination of Prenatal Substance Exposure Using Meconium and Orbitrap Mass Spectrometry

by Atakan Hernandez, Valerie Lacroze, Natalia Doudka, Jenny Becam, Carole Pourriere-Fabiani, Bruno Lacarelle, Caroline Solas and Nicolas Fabresse

Toxics 2022, 10(2), 55; https://doi.org/10.3390/toxics10020055 - 26 Jan 2022

Cited by 9 | Viewed by 4862

Abstract

The aim of this study was to develop and to validate a toxicological untargeted screening relying on LC-HRMS in meconium including the detection of the four main classes of drugs of abuse (DoA; amphetamines, cannabinoids, opioids and cocaine). The method was then applied to 29 real samples. Analyses were performed with a liquid chromatography system coupled to a benchtop Orbitrap operating in a data-dependent analysis. The sample amount was 300 mg of meconium extracted twice by solid phase extraction following two distinct procedures. Raw data were processed using the Compound Discoverer 3.2 software (Thermo). The method was evaluated and validated on 15 compounds (6-MAM, morphine, buprenorphine, norbuprenorphine, methadone, EDDP, amphetamine, MDA, MDMA, methamphetamine, cocaine, benzoylecgonine, THC, 11-OH-THC, THC-COOH). Limits of detection were between 0.5 and 5 pg/mg and limits of identification between 5 and 50 pg/mg. Mean matrix effect was between −79 and −19% (n = 6) and mean overall recovery between 18 and 73% (n = 6) at 100 pg/mg. The application allows the detection of 88 substances, including 47 pharmaceuticals and 15 pharmaceutical metabolites, cocaine and its metabolites, THC and its metabolites, and natural (morphine, codeine) and synthetic (methadone, buprenorphine, tramadol, norfentanyl) opioids. This method is now used routinely for toxicological screening in high-risk pregnancies Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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11 pages, 1026 KiB

Open AccessArticle

Thermal (In)stability of Atropine and Scopolamine in the GC-MS Inlet

by Gordana Koželj and Helena Prosen

Toxics 2021, 9(7), 156; https://doi.org/10.3390/toxics9070156 - 30 Jun 2021

Cited by 8 | Viewed by 4503

Abstract

The intoxication due to unintentional or intentional ingestion of plant material containing tropane alkaloids is quite frequent. GC-MS method is still widely used for the identification of these toxicologically important substances in human specimen. During general unknown analysis, high temperature of inlet, at least 270 °C, is commonly used for less volatile substances. Unfortunately, both tropanes are thermally unstable and could be overlooked due to their degradation. The temperature-related degradation of tropanes atropine and scopolamine was systematically studied in the inlet of a GC-MS instrument in the range 110–250 °C by increments of 20 °C, additionally also at 275 °C, and in different solvents. At inlet temperatures not higher than 250 °C, the degradation products were formed by elimination of water and cleavage of atropine’s ester bond. At higher temperatures, elimination of formaldehyde became predominant. These phenomena were less pronounced when ethyl acetate was used instead of methanol, while n-hexane proved unsuitable for several reasons. At an inlet temperature of 275 °C, tropanes were barely detectable. During systematic toxicological analysis, any tropanes’ degradation products should indicate the possible presence of atropine and/or scopolamine in the sample. It is not necessary to prepare thermally stable derivatives for confirmation. Instead, the inlet temperature can be decreased to 250 °C, which diminishes their degradation to a level where their detection and identification are possible. This was demonstrated in several case studies. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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Review

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21 pages, 383 KiB

Open AccessReview

Intrauterine and Neonatal Exposure to Opioids: Toxicological, Clinical, and Medico-Legal Issues

by Giuseppe Davide Albano, Corinne La Spina, Walter Pitingaro, Vanessa Milazzo, Valentina Triolo, Antonina Argo, Ginevra Malta and Stefania Zerbo

Toxics 2023, 11(1), 62; https://doi.org/10.3390/toxics11010062 - 9 Jan 2023

Cited by 2 | Viewed by 2581

Abstract

Opioids have a rapid transplacental passage (i.e., less than 60 min); furthermore, symptoms characterize the maternal and fetal withdrawal syndrome. Opioid withdrawal significantly impacts the fetus, inducing worse outcomes and a risk of mortality. Moreover, neonatal abstinence syndrome (NAS) follows the delivery, lasts up to 10 weeks, and requires intensive management. Therefore, the prevention and adequate management of NAS are relevant public health issues. This review aims to summarize the most updated evidence in the literature regarding toxicological, clinical, and forensic issues of intrauterine exposure to opioids to provide a multidisciplinary, evidence-based approach for managing such issues. Further research is required to standardize testing and to better understand the distribution of opioid derivatives in each specimen type, as well as the clinically relevant cutoff concentrations in quantitative testing results. A multidisciplinary approach is required, with obstetricians, pediatricians, nurses, forensic doctors and toxicologists, social workers, addiction specialists, and politicians all working together to implement social welfare and social services for the baby when needed. The healthcare system should encourage multidisciplinary activity in this field and direct suspected maternal and neonatal opioid intoxication cases to local referral centers. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

Other

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14 pages, 935 KiB

Open AccessFeature PaperEditor’s ChoiceSystematic Review

Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

by Luis Alberto Henríquez-Hernández, Jaime Rojas-Hernández, Domingo J. Quintana-Hernández and Lucas F. Borkel

Toxics 2023, 11(2), 148; https://doi.org/10.3390/toxics11020148 - 3 Feb 2023

Cited by 6 | Viewed by 6526

Abstract

Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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10 pages, 1067 KiB

Open AccessCase Report

Forensic Aspects of a Fatal Intoxication Involving Acetaminophen, Citalopram and Trazodone: A Case Report

by Giulio Mannocchi, Roberta Tittarelli, Flaminia Pantano, Francesca Vernich, Margherita Pallocci, Pierluigi Passalacqua, Michele Treglia and Luigi Tonino Marsella

Toxics 2022, 10(8), 486; https://doi.org/10.3390/toxics10080486 - 22 Aug 2022

Cited by 4 | Viewed by 4440

Abstract

We report the case of a young man, a former heroin addict, found dead at home by the Police Forces in an advanced state of decomposition. Numerous blisters and unpacked tablets of medications were found all over the bed and on the floor of the room. Multiple injuries to the face, left arm and neck of the deceased were noted. The latter damages were attributed to post-mortem dog bites, since no indications of a possible defense against the animal were observed. The autopsy findings were unremarkable. Toxicological investigations performed on peripheral blood and urine by gas chromatography-mass spectrometry (GC-MS) technique showed the presence of acetaminophen, citalopram and trazodone. Combined drug intoxication was proposed as the cause of death since acetaminophen and trazodone concentrations were comparable with the ones found in fatal cases. Moreover, citalopram concentration in peripheral blood was above the toxic range and in accordance with levels found in fatalities due to poly-drug intoxication. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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12 pages, 2511 KiB

Open AccessBrief Report

Detection of Morphine and Opioids in Fingernails: Immunohistochemical Analysis and Confirmation with Ultra-High-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry

by Roberto Scendoni, Emanuele Bury, Erika Buratti, Rino Froldi, Marta Cippitelli, Gianmario Mietti and Mariano Cingolani

Toxics 2022, 10(8), 420; https://doi.org/10.3390/toxics10080420 - 26 Jul 2022

Cited by 8 | Viewed by 2830

Abstract

This study aimed to investigate the detection of morphine in fingernails from forensic autopsies using immunohistochemistry (IHC), with confirmation by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). A primary antibody specific to morphine and a secondary antibody conjugated to horseradish peroxidase (HRP) was used. IHC on specimens of Subjects A and B (both drug addicts) resulted in the detection of morphine on a cell layer of the nail plate matrix. UHPLC-HRMS and GC-MS analysis showed that Subject A had a morphine concentration of 0.35 ng/mg in the fingernail and 472 ng/mL in the blood, while Subject B reached 1.23 ng/mg in the fingernail and 360 ng/ml in the blood. Most of those matrices were positive for codeine, methadone, EDDP, and 6-MAM. The use of IHC in Subject C (a former addict) showed no positivity for morphine in the fingernail, while the UHPLC-HRMS analysis confirmed its absence in the fingernail and blood. Additionally, an analysis of the scalp or pubic hair of the subjects was carried out using UHPLC-HRMS. The results suggest that IHC can be used to establish the site of accumulation of morphine in the nail matrix; for postmortem diagnosis; and that basic substances can be detected by UHPLC-HRMS. There are no previous studies on the use of IHC as a technique for forensic purposes in unconventional matrices, such as nails. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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9 pages, 4835 KiB

Open AccessFeature PaperCase Report

Forensic Toxicological and Medico-Legal Evaluation in a Case of Incongruous Drug Administration in Terminal Cancer Patients

by Pascale Basilicata, Pasquale Giugliano, Giuseppe Vacchiano, Angela Simonelli, Rossella Guadagni, Angela Silvestre and Maria Pieri

Toxics 2021, 9(12), 356; https://doi.org/10.3390/toxics9120356 - 16 Dec 2021

Cited by 7 | Viewed by 2887

Abstract

Background: In most cases, palliative care is prescribed to adults diagnosed with cancer. The definition of the most suitable therapy for an effective sedation in terminal cancer patients still represents one of the most challenging goals in medical practice. Due to their poor health, the correct dosing of drugs used for deep palliative sedation in terminal cancer patients, often already on polypharmacological therapy, can be extremely complicated, also considering possible drug-to-drug interactions that could lead to an increased risk of overdose and/or incongruous administration with fatal outcomes. The case of a terminal cancer patient is presented, focusing on the “adequacy” of administered therapy. Materials and Methods: A young male, affected by Ewing sarcoma, attending a palliative care at his own home, died soon after midazolam administration. Toxicological and histological analyses were performed on body fluids and organ fragments. Results and Discussion: Morphological reliefs evidenced a neoplastic mass, composed of lobulated tissue with a lardy, pinkish-gray consistency, extending from the pleural surface to the lung parenchyma, also present at the sacrum region (S1–S5), at the anterior mediastinum level, occupying the entire left pleural cavity, and infiltrating the ipsilateral lung. Metastatic lesions diffused to rachis and lumbar structures. The brain presented edema and congestion. Toxicological analyses evidenced blood midazolam concentrations in the range of 0.931–1.690 µg/mL, while morphine was between 0.266 and 0.909 µg/mL. Death was attributed to cardiorespiratory depression because of a synergic action between morphine and midazolam. The pharmacological interaction between midazolam and morphine is discussed considering the clinical situation of the patient. The opportunity to proceed with midazolam administration is discussed starting from guidelines recommendation. Finally, professional liability outlines are highlighted. Full article

(This article belongs to the Special Issue The Identification of Drug Abuse)

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