Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE).

Continuous development and rapid turnover of drug market of new psychoactive substances (NPS) make it difficult to obtain up-to-date analytical methods for efficient detection of intoxication cases with new substances: no analytical data and no previously published concentration values in biological samples are indeed available. In this context, we aim to report the first fatal case involving two newly emerging arylcyclohexylamine derivatives (a group of dissociative ketamine-based substances): 2-fluoro-deschloroketamine (2F-DCK) and 3-methoxyeticyclidine (3-MeO-PCE). A 42-year-old man was found dead at his home with three plastic bags of "research chemicals" powders near him. Comprehensive screenings of drugs and toxic compounds as well as more selective assays (performed using NMR, HS-GC-FID, LC-MS/MS and LC-HRMS methods) allowed (1) to identify the three unknown powders, 2F-DCK, 3-MeO-PCE, and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT, a hallucinogenic tryptamine-related NPS), with purity above 95%, and (2) to determine peripheral blood (1780, 90, and 52 µg/L), urine (6.1, 6.3, and 2.2 mg/L), bile (12, 3.5, and 1.7 mg/L), and vitreous humour (1500, 66 and 155 µg/L) concentrations of 2F-DCK, 3-MeO-PCE and 5-MeO-DMT, respectively. In addition, toxicological results also revealed recent use of cannabis, cocaine, and amphetamine by the victim, and hair analysis draw pathway of addiction (including experiments with various other NPS) for several months before death. This fatality was considered as the consequence of respiratory depression in a poly-drug user due to a "cocktail effect" of concurrent intakes of 2F-DCK (mainly), 3-MeO-PCE, 5-MeO-DMT, amphetamine, and cocaine. In addition, this case report provides analytical data that could support subsequent toxicological result interpretation in forensic cases involving such arylcyclohexylamine derivatives.

[The current situation of aggravated intoxication with "kiken" drugs (law-evading drugs)].

The intoxication caused by "kiken" drugs (law-evading drugs), such as synthetic cannabinoids, cathinones, and methoxetamine, has recently increased in Japan. We retrospectively examined the characteristics of patients poisoned with the "kiken" drugs. We included patients who presented at the emergency department at the Tokyo Metropolitan Bokutoh Hospital from January 2011 to December 2014. Eighteen patients admitted between January 2011 and December 2013 were included in the early period group and 10 patients admitted between January and December 2014 were categorized into the late period group. The number of the patients transported to our emergency department between 2011 and 2014 increased annually. Patients were mainly admitted between May and October 2014; no patients were admitted after November 2014. The patients' age, history of previous mental disease, habitual use, Triage DOA results, serum creatinine values on admission, and respiratory management differed significantly between the groups. However, the median serum creatinine values of both groups on admission were within the normal level. Patients poisoned with the "kiken" drugs showed more severe symptoms, higher rate of habitual use, and higher average age. The annual increase in the number of the patients observed thus far is expected to decrease in the future. Maintenance of the law and expansion of medical institutions that treat patients addicted to the "kiken" drugs are warranted.

Fatal intoxication with methoxetamine.

Methoxetamine (MXE) is a new synthetic drug of abuse structurally related to ketamine and phencyclidine. A case of a 29-year-old male with acute toxicity related to the analytically confirmed use of MXE is reported. The man was found dead at his residence. Biological material was analyzed using liquid chromatography-tandem mass spectrometry. The concentration of MXE in urine of the deceased was 85 µg/mL. Despite the vial containing the blood sample being destroyed during transportation and the blood leaking out into the cardboard packaging, the blood level of MXE was estimated. After determination of the cardboard grammage (approx. 400 g/m(3) ) and the mean mass of the blood obtained after drying (0.1785 ± 0.0173 g per 1 mL), the estimated blood concentration of MXE was found to be 5.8 µg/mL. The high concentration of MXE in blood and urine and the circumstances of the case indicate an unintentional, fatal intoxication with this substance.

A multicenter retrospective survey of poisoning after consumption of products containing synthetic chemicals in Japan.

OBJECTIVE: We conducted a multicenter retrospective survey of patients poisoned by synthetic chemicals (SCs) in Japan. METHODS: Letters were sent to 467 emergency facilities requesting participation in the study, and questionnaires were mailed to facilities that agreed to participate. Patients The study participants were patients who were transported to emergency facilities between January 2006 and December 2012 after consuming SC-containing products. RESULTS: We surveyed 518 patients from 60 (12.8%) facilities. Most patients were male (82.0%), in their 20s or 30s (80.5%), and had inhaled SCs (87.5%) contained in herbal products (86.0%). Harmful behavior was observed at the scene of poisoning for 56 patients (10.8%), including violence to others or things in 32, traffic accidents in seven, and self-injury or suicide attempts in four. Other than physical and neuropsychiatric symptoms, some patients also had physical complications, such as rhabdomyolysis (10.0%). Of the 182 patients (35.1%) admitted to hospitals, including 29 (5.6%) who needed respirators, all of the 21 (4.1%) hospitalized for at least seven days were male, and 20 had physical complications (rhabdomyolysis, 12; liver dysfunction, 5; renal dysfunction, 11; and physical injuries, 3). Most patients (95.6%) completely recovered, although 10 (1.9%) were transferred to a psychiatric department or hospital, and three (0.6%) were handed over to the police due to combative or violent behavior. SCs such as synthetic cannabinoids, synthetic cathinones, or methoxetamine were detected in 20 product samples. CONCLUSION: Consuming products containing SCs can result in physical complications, including rhabdomyolysis, injuries, and physical or neuropsychiatric symptoms, which may require active interventions, such as respirator use or prolonged hospitalization.

Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report.

Methoxetamine (MXE) is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gdansk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED) at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C) and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 µg/ml) was within the non-toxic range, while MXE (0.32 µg/ml) was within the toxic range of concentrations. Amphetamine was also detected in the patient's hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient's blood and urine suggest the possibility of adverse interactions between them.

[Acute methoxetamine intoxication--a case report with serum and urine concentrations]. / Ostre zatrucie metoksetamina--opis przypadku z wyznaczonymi stezeniami w surowicy i moczu.

Methoxetamine (MXE) is a novel synthetic drug, structurally related to phencyclidine, with ketamine-like properties. Available in Poland since 2010, with no legal control, is adverti. sed as the "ideal dissociation drug". The aim of this study was to present a case of nasal methoxetamine acute poisoning in a 28-year-old man, the course of treatment, and the method of identification of this substance in serum and urine. In the course of this intoxication extreme agitation and aggression with slight response to benzodiazepines were observed. The patient was confused, hallucinated. In addition, the physical examination re. vealed tachycardia 120/min and normal blood pressure (130/80 mm Hg). The period of acute poisoning was covered by amnesia. The MXE concentrations in serum and urine were determined using liquid chromatography-mass spectrometry (LC-MS-MS) method, and were respectively 270 ng/ml and 660 ng/ml. Confirmed MXE poisoning increases our knowledge about this new substance, providing relevant clinical and analytical data.

An accidental fatal intoxication with methoxetamine.

This paper reports an unintentional death involving the administration of methoxetamine [2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone] and offers some reference values from living drug abusers. Methoxetamine is a new recreational drug with a similar structure to ketamine. The deceased was a 26-year-old male with a history of drug abuse; he was found lying on the floor in his apartment. Several "red-line" plastic bags were found, one of which was labeled "2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone" and another labeled "Haze." In four cases from living subjects with unknown doses, concentrations of methoxetamine were found from 0.13 to 0.49 µg/g. In three of the cases, the blood samples also contained natural or synthetic cannabinoids. In the autopsy case, a considerably higher concentration of methoxetamine, 8.6 µg/g, was found in femoral blood. In addition, tetrahydrocannabinol and the three different synthetic cannabinoids AM-694, AM-2201, and JWH-018, were present in femoral blood. The circumstances and the high femoral blood concentration of methoxetamine point toward an unintentional, acute fatal intoxication with methoxetamine, although the presence of the three synthetic cannabinoids may have contributed to the death.

Accidental intoxication with high dose of methoxetamine (MXE)--a case report.

UNLABELLED: Methoxetamine (MXE) is an analogue of ketamine. CASE REPORT: We present a 25-year-old male who, after getting an information from the Internet, started to use MXE to avoid the excitement connected with recreational codeine abuse. For about 8 - 10 months he injected about 100 mg of MXE intramuscularly. On the day of admission the patient decided to take much higher dose of 750 mg of MXE. For the first 3-4 hours of hospitalization the profound agitation, which demanded the usage of high doses of benzodiazepines, was observed every several minutes. After 6-7 hours of supportive treatment the patient returned to his baseline mental status. CONCLUSION: MXE presents the new healthcare threat because of easy accessibility via Internet, and lack of legal restrictions in many countries. The low dose of MXE can cause "peace and serenity", however, higher dose may act opposite.

Out with the old, in with the new? Case reports of the clinical features and acute management of two novel designer drugs.

Methoxydine (4-MeO-PCP) and Methoxetamine (3-MeO-2-Oxo-PCE) are both commercially produced designer drugs with structural and biochemical similarities to phencyclidine (PCP). Although phencyclidine toxicity is well documented, its recreational use in present times is rare. With the advent of new designer drugs being available widely through internet sites, Acute Physicians should be aware of the clinical features and management of these potential toxins. We present a case of methoxydine ingestion (which to our knowledge has not been previously documented in any medical journals) and a case of methoxetamine ingestion, and discuss their history, contrasting clinical features and acute management.

Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation.

CONTEXT: There have been recent concerns about increasing use and accessibility of methoxetamine, a ketamine derivative. Few data are available to describe the clinical features associated with methoxetamine exposure. We report three cases that presented to hospital with acute neurological toxicity associated with analytically confirmed methoxetamine exposure. CASE DETAILS: A 19-year-old male presented with severe truncal ataxia, nystagmus, incoordination and reduced conscious level several hours after nasal insufflation of what was initially thought to be ketamine. Features of cerebellar toxicity persisted for 3-4 days before gradual recovery. Two more patients aged 17 and 18 years presented with severe cerebellar ataxia, imbalance and reduced conscious level 40 minutes after nasal insufflation of methoxetamine (MXE). Both had slurred speech, incoordination and cerebellar ataxia that resolved within 24 hours. Serum methoxetamine concentrations were 0.24 mg/L, 0.45 mg/L and 0.16 mg/L, respectively, and no other drugs were identified on an extended toxicological screen. DISCUSSION: Methoxetamine may cause rapid onset of neurological impairment, characterised by acute cerebellar toxicity. Spontaneous recovery was observed, but the duration of recovery may extend to several days. Presentation with an acute cerebellar toxidrome should alert clinicians to the possibility of methoxetamine exposure.

Ketamine-like effects after recreational use of methoxetamine.

Methoxetamine, the N-ethyl derivative of ketamine, is a novel recreational drug that is not at present subject to restrictive regulations in most countries. To our knowledge, no case of methoxetamine abuse has been published to date in the scientific literature, and the only sources of information are illegal drug users' Web discussion forums. We report the first case of analytically confirmed intravenous methoxetamine abuse in a 19-year-old man. Observed signs and symptoms such as tachycardia, hypertension, confusion, agitation, stupor, ataxia, mydriasis, and nystagmus were consistent with ketamine-induced adverse effects and resolved with symptomatic treatment. According to this case report, user Web reports, and the chemical structure, methoxetamine produces ketamine-like effects. Complete recovery can be expected with supportive care.