Case Report An accidental poisoning with mitragynine Ritva Karinen a, *, Jan Toralf Fosen a , Sidsel Rogde a,b , Vigdis Vindenes a a Norwegian Institute of Public Health, Division of Forensic Sciences, Box 4404, Nydalen, 0403 Oslo, Norway b Faculty of Medicine, University of Oslo, Norway 1. Introduction The number of available drugs encountered over the Internet are increasing, and names like ‘‘legal highs’’ and ‘‘herbal highs’’ could make the consumer believe these are safe and natural products [1]. The toxicity of these products is not known, and the amount of active substances ingested can vary widely, and constitute a major risk of fatal toxicity. Mitragyna speciosa Korth (Rubiaceae) is a tropical tree that is commonly found in Southeast Asia. Leaves from this plant, known as ‘‘Kratom’’ in Thailand and as ‘‘Biak-Biak’’ in Malaysia, have stimulant effects in low doses and sedative and opioid-like effects after ingestion of high doses [2,3]. Thai and Malaysian natives have traditionally consumed the leaves by chewing, smoking or drinking them as tea [4]. Mitragynine is considered to be the major constituent in the plant, and is responsible for the opioid effects through the m-receptor [5]. ‘‘Kratom’’ has been widely used as an opium substitute during opium withdrawal, as well as for pain relief [4]. ‘‘Krypton’’ is an herbal mixture containing powdered ‘‘Kratom’’ leaves and O-desmethyltramadol as a synthetic additive, and several deaths have been reported after ingestion of this drug [6,7]. Kikura-Hanajiri et al. [8] measured the contents of mitragynine and the minor alkaloid 7-hydroxymitragynine in ‘‘Kratom’’ products distributed as ‘‘incense’’ on the drug market, and mitragynine concentrations ranged from 1% to 6% and 7- hydroksymitragynine from 0.01% to 0.04%. From in vitro experi- ments and animal models, the potency of 7-hydroxymitragynine is reported to be 30–46 times higher than mitragynine [3,9–11] and 17 times higher than morphine [9]. The toxic mitragynine concentrations in humans are poorly defined, and no toxic or lethal ranges have been established. The structural formulae of mitragynine and 7-hydroxymitragynine are presented in Fig. 1. Studies have reported that Mitragyna speciosa preparations have analgesic, antipyretic, antidiarrheal, euphoric, anti-depres- sant, and anxiolytic effects, and the preparations have been used Forensic Science International 245 (2014) e29–e32 A R T I C L E I N F O Article history: Received 28 July 2014 Received in revised form 9 October 2014 Accepted 14 October 2014 Available online 24 October 2014 Keywords: Mitragynine 7-Hydroxymitragynine Forensic toxicology Drug fatality Blood drug concentration UPLC–MS/MS A B S T R A C T An increasing number of drugs of abuse are sold word wide over the internet. Names like ‘‘legal highs’’, ‘‘herbal highs’’ etc. give the impression that these are safe products, although the risk of fatal reactions might be substantial. Leaves from the plant Mitragyna speciosa, contain active compounds like mitragynine and 7-hydroxymitragynine. It has been reported that the potency of 7-hydroxymitragynine at the m-opioid receptor is 30 times higher than that of mitragynine and 17 times higher than that of morphine. Case reports regarding poisoning with Kratom are reported, but the toxic or lethal ranges for the concentrations of the active substances have not been established, and concentrations of 7- hydroxymitragynine have not been reported previously. We present a case report where a middle aged man was found dead at home. The deceased had a history of drug abuse and mental illness for several years. At autopsy, there were no significant pathological findings. Post-mortem analysis of peripheral blood revealed: zopiclone 0.043 mg/L, citalopram 0.36 mg/L and lamotrigine 5.4 mg/L, i.e. concentrations regularly seen after therapeutic ingestion of these drugs. Additionally mitragynine 1.06 mg/L and 7-hydroxymitragynine 0.15 mg/L were detected in blood and both also in urine. The high concentrations of mitragynine and 7-hydroxymitragynine indicate that the cause of death is intoxication by these substances; and the circumstances point toward the manner of death being accidental. We recommend that both mitragynine and 7-hydroxymitragynine are analyzed for in cases with suspected Kratom intoxication. ß 2014 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. E-mail address: ritva.karinen@fhi.no (R. Karinen). Contents lists available at ScienceDirect Forensic Science International jou r nal h o mep age: w ww.els evier .co m/lo c ate/fo r sc iin t http://dx.doi.org/10.1016/j.forsciint.2014.10.025 0379-0738/ß 2014 Elsevier Ireland Ltd. All rights reserved.