Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

Fatal α-PVP and amphetamine poisoning during a sauna and autoerotic practices.

We describe the sudden death of a middle-aged man while having a sauna under the influence of α-pyrrolidinovalerophenone (α-PVP) (PM blood concentration: 0.8 mg/L), amphetamine (0.34 mg/L), and other drugs (buprenorphine, benzodiazepines), and engaging in solitary sexual activities. The drugs' effects on the cardio-circulatory system and on body thermoregulation combined with the high temperatures are likely to have been central mechanisms leading to death. The high levels of adrenaline triggered by sexual arousal and the respiratory depression caused by buprenorphine, in association with benzodiazepines, may have also contributed to his death. This previously unreported type of accidental autoerotic death illustrates the risk of using amphetamine-like sympathomimetic drugs (e.g. cathinone derivates) in hot environments such as a sauna, and during sexual activities therein.

Acute poisoning among children and adolescents in southern Norway. / Akutt forgiftning blant barn og ungdom i Agder.

BACKGROUND: Self-inflicted poisoning is common in adolescents and is a risk factor for suicide. The aim of this study was to survey the circumstances surrounding hospitalisations due to acute poisoning in patients aged up to 18 years. MATERIAL AND METHOD: All hospitalisations in the Departments of Paediatric and Adolescent Medicine, Sørlandet Hospital Trust (Arendal and Kristiansand) due to acute poisoning in the period 1 August 2014-31 July 2015 were prospectively recorded with the aid of a form completed during the admission. RESULTS: There were 88 hospitalisations distributed among 68 adolescents (mean age 15.5 years, SD 1.5) and 13 children (mean age 2.8 years, SD 2.8). The poisoning was categorised as self-harm behaviour in 32 (47 %) of the adolescents, and as substance misuse-related in 35 (52 %). In total, 37 (54 %) of the adolescents had been or were under treatment at the Department of Child and Adolescent Psychiatry. Fifteen (22 %) of the adolescents were deemed to be suicidal. Thirty (94 %) of the adolescents who reported self-harm as the intention behind their poisoning were offered further follow-up at the Department of Child and Adolescent Psychiatry, along with 7 (20 %) of the group with substance misuse-related poisoning. INTERPRETATION: Adolescents who reported self-harm as their intention were usually offered further follow-up, whereas adolescents with substance misuse-related poisoning were rarely offered follow-up.

Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region - United States, 2006-2015.

Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration's (DEA's) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015.† In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

Multi-organ dysfunction due to bath salts: are we aware of this entity?

Methylenedioxypyrovalerone (MDPV) is a synthetic, cathinone-derivative, central nervous system stimulant taken to produce a cocaine- or methamphetamine-like high. Physical manifestations include tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, hyperkalaemia, disseminated intravascular coagulation, oliguria and seizures. We report a patient who presented with severe metabolic acidosis, multi-organ dysfunction, rhabdomyolysis, hyperkalaemia and seizures. This case highlights that even though a urine drug screen for routine psychostimulant drugs is negative, clinicians need to be vigilant about the adverse effects of MDPV as a possible cause of multi-organ dysfunction. Substances such as this can only be detected by special tests, such as gas/liquid chromatography mass spectrometry. This is the first reported case of MDPV toxicity successfully treated in Australia to the best of our knowledge.

New challenges in toxicology of new psychoactive substances exemplified by fatal cases after UR-144 and UR-144 with pentedrone administration determined by LC-ESI-MS-MS in blood samples.

The topic of this paper relates to the study of cases involving the use of new psychoactive substances (NPS) from the classes of synthetic cannabinoids and cathinones, analyzed from multiple viewpoints including clinical and medico-legal perspectives. The paper investigates three fatal cases in which UR-144 and UR-144 with pentedrone identified in the bodies of victims during post-mortem examinations were responsible for the tragic consequences and proved to be the indirect cause of death. The victims were men aged 16, 22 and 40 years who used drugs, for example they smoked marijuana or its substitutes in the form of synthetic cannabinoids. In addition, all of them had behavioural problems. On account of emotional imbalance attributable probably to the presence of UR-144 (in one case) and a mixture of UR-144 and pentedrone (in the other two cases), two men committed suicide by jumping from a height and hanging, and one man had fatal accidental poisoning with pentedrone which was used to enhance the effect of previously used UR-144. The presence of UR-144 and pentedrone in the post-mortem material was analyzed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS). The results of toxicological tests were analyzed with a focus on possible tragic side effects caused by the presence of UR-144 and UR-144 with pentedrone in the body.

Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

Novel psychoactive substances. / Nye psykoaktive stoffer.

There has been a significant increase in the number of new intoxicants on the illegal drugs market globally, also in Norway. The substances are given the name NPS: Novel Psychoactive Substances, and are mainly sold over the Internet. Uncertain dosage of potent substances entails a risk of accidental overdose, and therefore serious intoxication and death. In this article we provide an overview of current knowledge with regard to these substances.

Occurrence of the use of designer drugs in Poland--review of the published evidence.

Designer drugs are group of synthetic, semi-synthetic and natural substances used to induce effects similar to the effects of taking drugs. Despite the introduction of further legislation criminalizing the manufacture, trading and possession highs, they are still of interest to adolescents and young adults. The article contains a summary of the latest reports dealing with the spread of designer drugs among adolescents and young adults. It contains test results related to the frequency of use of designer drugs in different age groups, showing that they are much more frequently used than drugs. The scale of the phenomenon may also confirm data on the number of reported poisonings boosters. It is steady growth indicates health risks resulting from the use of designer drugs. It also emphasizes the need for immediate remedial action. It appears advisable to introduce other than questionnaire, methods of estimating the size of this phenomenon.

Severe Illness Associated with Reported Use of Synthetic Cannabinoids - Mississippi, April 2015.

On April 2, 2015, four patients were evaluated at the University of Mississippi Medical Center (UMMC) in Jackson, Mississippi, for agitated delirium after using synthetic cannabinoids. Over the next 3 days, 24 additional persons went to UMMC with illnesses suspected to be related to synthetic cannabinoid use; one patient died. UMMC notified the Mississippi State Department of Health, which issued a statewide alert via the Health Alert Network on April 5, requesting that health care providers report suspected cases of synthetic cannabinoid intoxication to the Mississippi Poison Control Center (MPCC). A suspected case was defined as the occurrence of at least two of the following symptoms: sweating, severe agitation, or psychosis in a person with known or suspected synthetic cannabinoid use. A second statewide alert was issued on April 13, instructing all Mississippi emergency departments to submit line lists of suspected patients to MPCC each day. By April 21, 16 days after the first alert was issued, MPCC had received reports of approximately 400 cases, including eight deaths possibly linked to synthetic cannabinoid use; in contrast, during April 2012­March 2015, the median number of telephone calls to MPCC regarding synthetic cannabinoid use was one per month (range = 0­11). The Mississippi State Department of Health, with the assistance of CDC, initiated an investigation to better characterize the outbreak, identify risk factors associated with severe illness, and prevent additional illnesses and deaths.

Notes from the Field: Increase in Reported Adverse Health Effects Related to Synthetic Cannabinoid Use - United States, January-May 2015.

On April 6, 2015, CDC received notification of an increase in telephone calls to U.S. poison centers related to synthetic cannabinoid use. Monthly calls to all poison centers are tracked by the National Poison Data System, which reported that adverse health effects or concerns about possible adverse health effects related to synthetic cannabinoid use increased 330% from 349 in January 2015 to 1,501 in April 2015. Synthetic cannabinoids include various psychoactive chemicals or a mixture of such chemicals that are sprayed onto plant material, which is then often smoked or ingested to achieve a "high." These products are sold under a variety of names (e.g., synthetic marijuana, spice, K2, black mamba, and crazy clown) and can be sold in retail outlets as herbal products. Law enforcement agencies have regulated a number of these substances; however, manufacturers of synthetic cannabinoids frequently change the formulation to avoid detection and regulation. After the initial notification, CDC analyzed information from the National Poison Data System on reported adverse health effects related to synthetic cannabinoid use for the period January-May 2015.

Severe poisoning after self-reported use of 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, a novel substituted amphetamine: a case series.

Significant toxicity from amphetamine and cathinone derivatives is being increasingly reported. We describe a series of self-reported exposures to 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25-I-NBOME or 25-I), a novel amphetamine derivative. Ten patients with an average age of 17 years presented to local emergency departments (EDs) in our community after ingestion and/or insufflation of a drug referred to as "25-I." Of 10 patients, 6 reported taking 25-I alone; other substances included ethanol; 2,5-dimethoxy-4-ethylphenethylamine; marijuana; and ketamine. Most common effects included tachycardia (90%), hypertension (70%), agitation (60%), and hallucinations (50%). The average heart rate was 123 beats per minute. Two patients were found in status epilepticus, and another was found unresponsive. One patient who had a seizure had multiple, discrete intraparenchymal hemorrhages and acute kidney injury. Six patients were admitted to the intensive care unit, two were treated in the ED and released, and 1 each was admitted to psychiatry or managed in a clinical decision unit and subsequently discharged. Three patients required emergent intubation, and all admitted patients (7/10) were given intravenous benzodiazepines for sedation. Urine and blood specimens were obtained from 1 patient, which showed analytic confirmation of 25-I. In addition to sympathomimetic effects, methoxy and other substituent groups impart serotonergic effects, resulting in hallucinogenic properties. 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine appears to be extremely potent with a reported "dose" of 500 µg resulting in increased potential for inadvertent overdose. This case series describes significant morbidity in a local cluster of young patients after self-reported use of 25-I, a newly identified drug of abuse.

[New psychoactive substances and their prevalence in the Czech Republic]. / Nové psychoaktivní látky a jejich výskyt v Ceské republice.

Recently, there is a global growing concern over the new (mainly synthetic) psychoactive substances, known as legal highs, research chemicals or bath salts. They are represented by various chemical groups imitating "old" illicit drugs with stimulant, euphoric, hallucinogenic or sedative effects. In the Czech Republic, the peak of their use and supply was observed at the beginning of 2011, when new psychoactive substances were available in smart shops known locally as Amsterdam shops - in that time mainly synthetic cathinones and also synthetic cannabinoids were present. After legislative change that placed tens of new substances under the control of criminal law in April 2011, new psychoactive substances are available at Internet and their use is (after short and media driven boom in early 2011) rather limited and decreasing. Though, the use of new synthetic stimulants was recently reported locally among problem (injecting) drug users; new very potent synthetic opioids represent potential threat of further expansion in this users subgroup.

[Analysis of intoxication with novel psychoactive substance (NPS) in Pomeranian region, from January to July 2015]. / Analiza zatruc nowymi substancjami psychoaktywnymi (NPS) w województwie pomorskim, w okresie od stycznia do lipca 2015 r.

INTRODUCTION: During initial months of the year 2015 we observed the increase number of patients intoxicated with NPS in Poland. In our work we analysed the scale of this phenomenon in Pomeranian region. MATERIALS AND METHODS: Study was carried out on period from 1 January 2015 to 31 July 2015. Analysis was based on records derived from Electronic Poison Information Database developed and used on a daily basis on Pomeranian Centre of Toxicology (PCT), data obtained from Centre for Monitoring of Adverse Effects of Medicaments and Chemical Substances based in PCT and on information gathered from patients treated in Pomeranian Centre of Toxicology for NPS intoxication. RESULTS: Our study has shown slow, continuous rise in the number of intoxications with NPS in analysed period. The most frequent cause of intoxication were synthetic compounds. 99 cases needed treatment in Clinical Toxicology Unit due to their severe state. The youngest exposed person was 13 y.o., while the oldest was 53 y.o. Mean age was 22.5 y.o. with median 20 years. Majority of intoxications were among males (80.54%). 61.53% of all patients came from Tricity agglomeration. Ethanol was the prevalent coingestant. The most commonly used substance was generic NPS (70.59% of cases), followed by unknowns psychoactive substance (16.29% of cases), herbal mixture (16.29% of cases) and dextrometorphan (5.88% of cases). The study did not find one drug name that would be prevalent over others, with the most frequent commercial name being "Mocarz", found in 4 cases. Most dangerous substances found in NPS were PMA, PMMA, 25C-NBOMe and 251-NBOMe. There were no deaths of patients treated in PCT because of acute intoxication with NPS.

[Designer-drug overdose patients treated by Helsinki Emergency Medical Services in 2009-2012]. / Muuntohuumeita käyttäneet yliannostuspotilaat Helsingin ensihoidossa vuosina 2009-2012.

BACKGROUND: Designer drug abuse has increased during the last decade. MATERIAL AND METHODS: Retrospective study of designer drug overdoses in Helsinki emergency medical services (EMS) 2009-2012. Use of drugs was self-reported or from other people present. RESULTS: There were 98 patients (72% male), median age 30 years. The majority reported MDPV and polysubstance abuse. Only 15% were administered medication by EMS and 69 were transported. In the emergency department 53% required specific care, mostly benzodiazepines. Most (78%) were discharged within less than 24 hours. Infectious complications were the main reason for admission. CONCLUSIONS: Designer drug overdose patients require drug administration rarely on scene, but quite often in the emergency department, usually sedation. Admissions are rare.

Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following "bath salts" injection.

"Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction.

The electric Kool-Aid NBOMe test: LC-TOF/MS confirmed 2C-C-NBOMe (25C) intoxication at Burning Man.

Designer drugs are constantly evolving, with the NBOMe derivatives of the 2C class of phenethylamines recently emerging in the US market. Cases of 2C-I-NBOMe toxicity have recently been reported in the literature. No reports to date describe the clinical effects 2C-C-NBOMe toxicity.

'Designer drugs': update on the management of novel psychoactive substance misuse in the acute care setting.

The use of novel psychoactive substances ('legal highs' or 'designer drugs') is increasing worldwide. Patients misusing such substances have been reported to experience severe or prolonged side effects requiring admission to acute or critical care wards. These complications can be life threatening if misdiagnosed or mismanaged. As physicians have traditionally had less involvement with the management of such patients compared with their colleagues in emergency departments an update in the management of such patients is indicated. Here we present a summary of the management of those novel substances with the potential for serious complications based on a review of current literature.

[MT-45--a dangerous and potentially ototoxic internet drug]. / MT-45 - en livsfarlig och potentiellt ototoxisk internetdrog.

During the last years several synthetic opioids have been introduced on Internet sites selling new psychoactive substances (NPS). One of these, called MT-45, a piperazine derivative originally synthesized as a therapeutic drug candidate in the 1970s, has recently been detected in 21 deaths, according to unpublished data from the Swedish National Board of Forensic Medicine. We present clinical data from 12 analytically confirmed hospital cases of MT-45 poisoning. The cases demonstrate that MT-45, like other opioids, can induce potentially life threatening respiratory depression and loss of consciousness in users and that symptoms are usually reversed by standard doses of the opioid receptor antagonist naloxone. Significant auditory symptoms with transient tinnitus and hearing loss occurred in two cases and a pronounced sensorineural hearing loss still present at two weeks follow-up in one case. This indicates that MT-45 may be an ototoxic substance, illustrating the ubiquitous risk of unintended adverse effects NPSs pose to users.

["Spice"--synthetic cannabinoids with dangerous effects]. / ¼Spice« - syntetiska kannabinoider med riskabla effekter - Fall av akut njursvikt och cerebral ischemi med stroke har rapporterats.

Synthetic cannabinoids are a large group of chemicals functionally related to delta-9-tetrahydrocannabinol (THC) found in Cannabis sativa. These compounds are full agonists on cannabinoid receptors, therefore more potent than THC. Products marketed over the Internet intended for abuse usually consist of dried inert plant material sprayed with different kinds of cannabinoids. Smoking is the most common route of administration. In Sweden commercially available products are usually labeled ¼spice«. A case concerning a young male with convulsions and acute kidney failure requiring temporary dialysis is presented. Other reported serious effects of this group of substances are acute psychosis, unconsciousness, cardiac ischemia, seizures and stroke. The vendors are very aware of the legal situation in each country and adjust their supply according to current narcotics classifications. New, previously unknown cannabinoids are constantly appearing on the market.