Mitragynine ‘Kratom’ Related Fatality: A Case Report with Postmortem Concentrations

Journal of Analytical Toxicology 2015;39:152 –155 doi:10.1093/jat/bku137 Advance Access publication December 16, 2014 Case Report Mitragynine ‘Kratom’ Related Fatality: A Case Report with Postmortem Concentrations Iain M. McIntyre*, Amber Trochta, Susan Stolberg and Steven C. Campman County of San Diego Medical Examiner’s Office, 5570 Overland Ave., Suite 101, San Diego, CA 92123, USA *Author to whom correspondence should be addressed. Email: A 24-year-old man whose medical history was significant for alcohol abuse and depression was found unresponsive in bed. He had several prior suicide attempts with ‘pills’ and had also been hospitalized for an accidental overdose on a previous occasion. Autopsy findings were unremarkable apart from pulmonary edema and congestion, and urinary retention. Postmortem peripheral blood initially screened positive for mitragynine ‘Kratom’ (by routine alkaline drug screen by gas chromatography –mass spectrometry, GC–MS), which was subsequently confirmed by a specific GC–MS selective ion mode analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.23 mg/L), central blood (0.19 mg/L), liver (0.43 mg/kg), vitreous (<0.05 mg/L), urine (0.37 mg/L) and was not detected in the gastric. Therapeutic concentrations of venlafaxine, diphenhydramine and mirtazapine were also detected together with a negligible ethanol of 0.02% (w/v). The results are discussed in relation to previous cases of toxicity, and the lack of potential for mitragynine postmortem redistribution. Introduction Mitragynine (Figure 1) is the primary indole alkaloid extracted from the leaves of the rubiaceous plant Mitragyna speciosa. Kratom, which may contain over 25 different alkaloids, is the name given to the leaves and preparations from the species. It is commonly chewed, smoked or brewed as tea in Southeast Asia where it has been used for hundreds of years. It was reported in 2005 to have significant abuse potential in the USA. (1). Marketed as a euphoriant dietary supplement, ‘incense’ or ‘legal opioid’, at low doses it has been described to produce stimulant effects, while at higher doses it produces sedative and euphoric effects. It is sold as tablets, capsules, concentrated extracts or chopped leaves as ‘Kratom’ or ‘Krypton’ (2). The effects are generally noted within 5– 10 min of ingestion and may last up to 6 h (3). The pharmacology and toxicity of mitragynine are not fully understood. However, the coca-like stimulant and opium-like sedative effects are most likely due to its dual binding to a-adrenergic and opioid-m receptors (4). Case studies have reported individuals self-medicating with Kratom for pain management being admitted to the hospital following seizures (5, 6). Other adverse side effects reported by users include nausea, vomiting, diarrhea and tolerance development. Withdrawal symptoms were also reported upon terminating use (2). Users who combine the drug with central nervous system depressants can experience respiratory depression (3). Despite descriptions of toxicity and even drug-related deaths, there are limited reports of biological mitragynine concentrations. A urine concentration of 0.167 mg/L was found in a man suffering a seizure following Kratom use (5). Kronstrand and colleagues (7) presented postmortem blood concentrations ranging from 0.02 to 0.18 mg/g in nine cases of accidental intoxication where both mitragynine and O-desmethyltramadol were detected. A fatality, attributed to propylhexedrine toxicity, found mitragynine together with low concentrations of morphine, promethazine and acetaminophen (8). Their investigation of tissue distribution revealed the highest mitragynine concentration in urine (1.2 mg/L) with other tissues being heart blood (0.39 mg/L), liver (0.12 mg/kg), vitreous (0.15 mg/L), kidney (0.16 mg/kg), spleen (0.18 mg/kg), lung (0.01 mg/kg) and bile (0.48 mg/mL). Another mixed drug-related fatality was reported where mitragynine ( postmortem blood concentration of 0.60 mg/L) was considered a contributing factor together with dextromethorphan, diphenhydramine, temazepam and 7-aminoclonazepam (9). We describe a death attributed to mixed drug toxicity— primarily mitragynine. The current report revealed the detection of mitragynine by routine toxicology screening, describes a specific gas chromatography –mass spectrometry selective ion mode (GC–MS SIM) analysis and presents the postmortem concentrations in peripheral blood, central blood, liver, vitreous, urine and gastric contents. Methods Case report The decedent was a 24-year-old man whose medical history was significant for alcohol abuse and depression. He had been drinking alcohol since age 15, had several suicide attempts with ‘pills’ and had been hospitalized for an accidental overdose. His mother spoke with him by phone the night before his death and he sounded fine to her and he had no complaints. Less than 1 h later a friend picked him up from his residence and described him as appearing ‘out of it’, tired and depressed. They drove to the friend’s residence and watched television for about an hour, and during that time the decedent reportedly consumed a glass of wine and a beer. He then took a ‘sleeping pill’ and they retired to bed at approximately midnight. At 03:00 h, the friend awoke because the decedent was encroaching on his sleeping space, but could not move him and found that he was cold and unresponsive. The friend called rescuers at 03:03 h, moved the decedent to the floor and started chest compressions. Medics arrived at 03:07 h and initiated advanced resuscitative efforts. Resuscitation was unsuccessful and he was declared dead at 03:30 h. Vomitus was noted on the bedding and around the decedent’s head on the floor. The decedent’s belongings contained prescription bottles for venlafaxine (75 mg), mirtazapine (15 mg) and omeprazole (20 mg). Pill counts of the remaining medications, from the bottles collected at the scene, suggested that he had taken the amounts prescribed—or even less than prescribed. A loose loperamide caplet (2 mg) was also among his possessions. # The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: Figure 1. Structure of mitragynine. An autopsy was performed (beginning 29.5 h after death was declared) and documented pulmonary edema and congestion (950 g, right lung; 890 g, left lung), moderate urinary retention (300 mL) and no natural disease or trauma. Postmortem specimen collection All specimens analyzed were collected at autopsy at the San Diego County Medical Examiner’s Office. Peripheral blood (20 mL) was drawn from the left common iliac vein (blood returning from the leg and visually identified in the pelvis at autopsy) and stored in standard glass tubes containing sodium fluoride (100 mg) and potassium oxalate (20 mg). Central blood was collected from the intra-pericardial inferior vena cava and placed in identical tubes. Vitreo (...truncated)