The literature search resulted in 380 sources after elimination of duplicates. Epub 2006 Jun 30. Herbal blends, smoking devices (e.g., pipes) and other paraphernalia were found during the death scene investigation (DSI) in 30 of 74 cases (41%) and were variably labeled as Aladdin platinum/limited, Herbal incense, the super lemon, F1, Hammer Head, Magic Gold, Desert Premium Potpourri, AL 37, AP 31, Strongman, GM sapphire, Heart Shot Black, Apollo, Mocarz, Smoke XXX. In almost the totality of cases, a possible involvement of SCRAs was suggested by either a past history of drug/alcohol abuse, by witnesses' statements of partying or smoking shortly before collapse, or by the DSI, which revealed paraphernalia and herbal residues. A complete and accurate post-mortem examination is a fundamental part in the evaluation of death cases involving SCRAs, since a comprehensive and multi-disciplinary evaluation of clinical, circumstantial, toxicological, and autoptic data is the only possibility to assess the toxicological significance of a substance and to tentatively identify a plausible mechanism of death, which could remain unclear despite an in-depth analysis of all data available. Finally, a total of 34 manuscripts were included (authors, title, journal, date of publication, and involved SCRAs are shown in Table 1), corresponding to 74 published cases. Synthetic cannabinoids or synthetic cannabinoid receptor agonists (SCRAs) are a heterogeneous group of compounds designed to mimic the effects of delta-9-tetrahydrocannabinol (9-THC) by binding to the cannabinoid receptors CB1 and CB2. Westin AA, Frost J, Brede WR, Gundersen PO, Einvik S, Aarset H, et al. Similarly, a contributory role was stated by Tse et al. 2000;37:2044. Because of the complexities of forensic testing, few if any laboratories can do all the types of testing that may be required. There are no specific standards of competence for individual forensic practitioners as yet in the UK other than pathologists, who undertake examinations to become Fellows of the Royal College of Pathologists and undertake further training before admission to the Ministry of Justice register. Post-mortems are carried out by pathologists (doctors who specialise in understanding the nature and causes of disease). From these tissues, samples may be taken for microscopic examination. Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, et al. FOIA Death due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids. Solimini R, Busard FP, Rotolo MC, Ricci S, Mastrobattista L, Mortali C, et al. 2003;41:47-56. Lack of material represents a serious limitation particularly in the case of measured concentrations being far above the linear range of the calibration, even though results might be estimated by extrapolation (27, 38, 43). The results of toxicological analyses should be interpreted with caution, considering the many confounding and influencing factors, particularly regarding the reliability of LC-MS/MS methods validated insufficiently or validated only in serum. Rapid degradation due to pyrolysis, ante-mortem drug metabolism, as well as post-mortem redistribution and degradation (due to remaining esterase activity) were considered as further main factors for reduced concentrations and should be considered for all SCRAs, though with different weighting (19, 23, 44). Pacher P, Steffens S, Hask G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Correlation of phenobarbital and diphenylhydantoin levels with plasma, Distribution of anticonvulsant drugs in gray and white matter of human brain, Canadian Journal of Neurological Sciences, Carbamazepine and carbamazepine-10, 11-epoxide concentrations in human brain, The Author 2014. PubMed Identification and quantification of predominant metabolites of synthetic cannabinoid MAB-CHMINACA in an authentic human urine specimen. Brain tissue may be a valuable specimen in interpretation of postmortem toxicology. Best-practices approach to determination of blood alcohol concentration (BAC) at specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling and post-mortem alcohol generation and transport considerations. The brain undergoes less PMR (8) and brain concentration has been found to be more stable over time when compared with other sample sites (4). Flanagan RJ, Connally G, Evans JM. Post-mortem assessment and evolutionary role of the bio-medicolegal sciences. Cardiac arrhythmias and cardio-circulatory acute effects were listed in 17 cases (23%) as cause of death or as underlying mechanisms in a group of mono and poly-drug intoxications, involving both teenagers and adults (20, 21, 35, 40, 48). Forensic Sci Res 1:4251, CrossRef AWMF Leitlinien-Register Nr. Exclusion criteria were: irretrievability of a full-text; off-topic articles (e.g., death cases in which other NPS, but no SCRAs, were detected); in vitro/animal model studies; herbal blends analyses; non-fatal cases of intoxication; books/reviews not including unpublished cases of death due to SCRAs; autopsy/external examination not performed. Ref, reference; age, -s: decade (e.g., 30s: from 30 to 39 years old); PBC, peripheral blood concentration; m, metabolites; pos, positive; NP, not provided; TSS, Toxicological Significance score. Labs look at these DNA sequences for matches between the presented evidence and suspects based on sequences of small segments of DNA at different locations on the person's total genetic makeup (genome). Although the sample size is small, there appears to be some overlap in the ratios, which would not be unexpected. type of victim, referring to age and sex; concentrations of SCRA retrieved during toxicological analyses in central and peripheral blood, urine, and tissues; circumstantial data (and whatever relevant emerged during the death scene investigation), with particular reference to a history of drug abuse and to the availability of herbal blends/paraphernalia at the scene. 2021 Apr 21;6(17):11563-11569. doi: 10.1021/acsomega.1c00773. In the case described by Langford et al., for example, the analyses were granted by a private licensed forensic laboratory, and no information was disclosed due to alleged competition and market issues (20). If an individual is convicted of a crime, his or her genetic fingerprint (a select list of DNA polymorphisms) is put into the database. The quantitative studies were performed using standard validated chromatographic (GCNPD or GCMS) methods used during the routine examination of the specimens. This is a preview of subscription content, access via However, the mechanism of death could remain unclear, despite having a more complete data set (40) and the agreement between independent reviewers judging the very same pieces of information could be weak (e.g., unanimous agreement in 2 cases out of 25 submitted to multiple evaluations) (33, 40). Google Scholar. Case report: fatal intoxication with synthetic cannabinoid MDMB-CHMICA. Results of post-mortem examination, as for macroscopical or gross findings, were available in 55 cases (74%), including those cases in which only a short referral to unremarkable findings was reported. Acute liver injury, severe coagulopathy, acute kidney injury, acute respiratory failure, hypoxemia, severe anion gap metabolic and lactic acidosis. (2) found that with a high volume of distribution, high PMR is expected. This is due to several factors, the measured drug concentration at the time of death may not reflect complete distribution, that is, acute overdose and/or PMR may skew the relationship. National Library of Medicine The study groups together a wide range of cases and circumstances. Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22. Gastro-intestinal symptoms with nausea and vomiting are also common. Interpretation of postmortem drug blood concentrations presents many challenges. Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to (9)-THC: mechanism underlying greater toxicity. Forensic medicine: Hypothermia after the use of SCRAs was seen in experimental studies on animals (e.g., male rats and monkeys) (73, 74) and has been partially related to the effects of cannabinoids on dopamine receptors (75), but has not been confirmed in humans yet. Copyright 2015 | Toxicology And DNA Global Services. Some general trends in drugs belonging to the same structural or pharmacological class are observed in TableI data. In some cases, stomach and gastroduodenal erosions (20, 35), abundant hypostasis coupled to petechiae (27, 29, 37) and intracutaneous skin bleedings (vibices) (30) were reported. Conducting toxicology on post-mortem specimens provides a number of very significant challenges to the scientist. In cases where biological family relationships are at issue, DNA tests can either include or exclude a presumed parent, sibling, or other familial relationship that may exist using a mathematical estimation called a "paternity" or "relationship index." Epidemiological approaches by reviewing large numbers of related cases are the most powerful tool to obtain this information. Forensic Toxicology Service Mean age was 32, median 29. Histological data, as a specific result of a microscopical analysis, was clearly described only in 13 cases (18%). Blood submitted should be taken from the femoral vein in order to minimise the effects of post-mortem redistribution. Post-mortem toxicology of commonly-abused drugs - ScienceDirect Current role of liquid chromatography-mass spectrometry in clinical and forensic toxicology. Search for other works by this author on: Disposition of Toxic Drugs and Chemicals in Man, The extent of postmortem drug redistribution in a rat model, Postmortem redistribution of THC in the pig, Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography-mass spectrometry, Distribution of drugs of abuse within specific regions of the human brain, Postmortem redistribution of the enantiomers of citalopram and its metabolites: an experimental study in rats, Mechanisms underlying postmortem redistribution of drugs: a review, Therapeutic brain concentration of the NMDA receptor antagonist amantadine, Regional distribution of cocaine in postmortem brain of chronic human cocaine users, Regional distribution of methamphetamine in autopsied brain of chronic human methamphetamine users, Phenytoin concentrations in the human brain: an in vivo microdialysis study, Distribution of venlafaxine, o-desmethylvenlafaxine, and o-desmethylvenlafaxine to venlafaxine ratio in postmortem human brain tissue, Anticonvulsant drugs in human epileptogenic brain. Of the 34 manuscripts, 8 consisted in case series and 26 in case reports, including articles only providing new analytical data on previously reported death cases (Table 1). Pathology involves the study of changes in the body caused by disease or injury. C/P ratios of 1.75 to 1.54 were also seen by Hasegawa et al. Opioids generally tended to have a heart blood concentration that is about half of the brain concentration. Argo A, Zerbo S, Buscemi R, Trignano C, Bertol E, Albano GD, Vaiano F. Toxics. After smoking two different SCRAs in a day and drinking a beer, he was wheezing, vomited and then lost consciousness. Papaver somniferum in seventeenth century (Italy): archaeotoxicological study on brain and bone samples in patients from a hospital in Milan. Forensic Laboratory Testing: What Is It? Provided by the Springer Nature SharedIt content-sharing initiative, Forensic Science, Medicine, and Pathology, https://doi.org/10.1007/s12024-010-9150-4, access via Toxicology testing is also undertaken in an attempt to ascertain if either a suspect, or the deceased might have been under the influence of drugs at the time of death. Stuttgart: 9. This can occur during life, and in some circumstances is likely or inevitable. (10) observed only slight regional differences in brain tissue for cocaine and its metabolites (benzoylecgonine, ecgonine methylester, norcocaine and cocaethylene). Toxicology testing not only includes investigations of driving under the influence of alcohol or drugs, but also testing for illicit or performance-enhancing drugs in athletes, and testing for substance abuse in the workplace. In a case described by Labay et al. Presumptive identification of nitrite by Griess reagent test strips . Forensic pathologists are experts in histopathology, which deals with structural alterations of the human body, and may become experts in related areas such as forensic toxicology, which is concerned with poisoning and the effects of poisons on the body. Found dead after 1.5 h, Known user of SC, found dead on the floor of the bedroom. (5) determined distribution of antidepressants throughout the brain to be homogeneous. Alprazolam and zolpidem have relatively low volumes of distribution and are less likely to undergo PMR when compared with weakly basic drugs with higher volumes of distribution. Price excludes VAT (USA) The postmortem redistribution of iso--acids in postmortem specimens. FOIA Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE, Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages postmortem. Forensic Science, Medicine, and Pathology Willeman T, Allibe N, Sauerbach L, Barret A, Eysseric-Guerin H, Paysant F, Stanke-Labesque F, Scolan V. Int J Legal Med. Signs and symptoms of SCRAs consumption include psychomotor agitation, euphoria, anxiety, confusion, and psychosis on the one side, sedation and loss of consciousness on the other (9, 10). SCRAs are not detected by common immunoassays and require a target analysis, which is usually only requested by authorities and conducted when a suspicion is raised, due to analytical limitations and economic reasons (21). DNA typing is not the same as the in-depth, highly complex, full genomic sequencing often heard about in the news. However, tests to identify unknown toxins, such as mass spectrometry and liquid chromatography, tend to be much more expensive. Testing may be repeated six weeks to six months after the incident to help determine if the incident resulted in pregnancy and/or infection. Morphine, however, has a high Vd of 25 L/kg, yet has a high HB/Br of 1.47. Patients rushed to the emergency department and subsequently died were also included in the selected cases. The site is secure. All causes of death are represented. The post-mortem also includes dissection and measurement of the internal organs. 1Legal Medicine and Toxicology, University-Hospital of Padova, Padova, Italy, 2Institute of Forensic Medicine, Forensic Toxicology, Medical Center, University of Freiburg, Freiburg, Germany, 3Section of Legal Medicine, Department of Excellence SBSP, University Politecnica delle Marche of Ancona, Ancona, Italy, 4Unit of Forensic Toxicology, SAIMLAL Department, Sapienza University of Rome, Rome, Italy, 5Faculty of Medicine, University of Freiburg, Freiburg, Germany. Br J Clin Pharmacol. Anxiety and psychosis might be also explained by the affinity of SCRAs to dopaminergic (D2), serotoninergic (5-HT2A) or glutamatergic (NMDA) receptors (76, 77). The potential for postmortem changes must be considered in all but a few drugs. Correspondence to There is a positive correlation of blood to brain concentrations, thus providing another tool for the toxicologist or pathologist to utilize in case interpretation. The absence of a clearly stated methodology and validation process questions the reliability of the analytical results and limits the comparability of the data. (45) found signs of hypertension and aging in a 20-year-old victim, coupled to myocardial suffering, and thus hypothesized a cardio-circulatory hyperactivity due to prolonged SCRA use. Am J Forensic Med Pathol. A toxicologist works closely with police, pathologists and the Crown Office and Procurator Fiscals Service to determine the type of analysis required. testing. The purpose of a toxicology investigation on postmortem specimens is to examine whether alcohol, legal or illegal drugs or other substances are directly or indirectly considered as being the cause of death, or whether they have caused incapacity to act or have drugged a victim to incapacitation. An official website of the United States government. Blood and urine are routinely analysed for ethanol. Very sensitive methods are needed in blood, given the low concentrations reported in the literature (52) and urine analysis can reveal a previous intake even when nothing is detected in blood (22, 23). Inclusion in an NLM database does not imply endorsement of, or agreement with, Post-mortem toxicology A forensic toxicologist might get involved in a post-mortem investigation if poisoning was not suspected initially as the cause of death. 2003;27:53344. Forensic testing isn't always the way it appears on TV. 8600 Rockville Pike to provide an updated analysis of the post-mortem toxicology practices of DRD cases in Europe and to discuss the effect of these practices on the monitoring of DRDs. More recent advances also include accurate mass spectrometry. Pitfalls in forensic toxicology - SAGE Journals In 8 cases (11%) only heart blood concentrations were stated, while both peripheral and central concentrations were published in 10 cases (14%). Postmortem Toxicology: Can the Dead Tell Their Stories? several processes such as a non-uniform distribution of the drug within the body, a release from its binding sites and/or passive diffusion, Extraction of specimens for toxicological analysis, should be performed on skin and subcutaneous fat if solvent abuse or an anaesthetic death is suspected, the date of receipt for the postmortem examination of the corpse, Skopp, G. Postmortem toxicology. The protected and isolated position of the brain eliminates or at least attenuates many of the interpretive challenges with postmortem blood specimens. (64) despite morphological findings which could have explained the death by themselves. In most cases in which a SC was later discovered during toxicological analysis, the post-mortem examination had revealed only non-specific signs of intoxication, such as pulmonary edema and congestion, brain edema, hemolysis, and signs of aspiration (34, 40). 2017 Jul;131(4):1085-1101. doi: 10.1007/s00414-017-1585-7. With reference to the gender of the victims, 88.1% were male and 11.9% were female. The age of the deceased ranged from 14 to 61 (19). The decedent was lying on the floor in a supine posture. Other volatiles including acetone and methanol are simultaneously detected using the same method of analysis. Nevertheless, reasonable assessments can still be made by the pathologist and toxicologist as to the contribution that commonly-abused drugs may have made to the death.
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