Alphonse Poklis

A case of 25I-NBOMe (25-I) intoxication: a new potent 5-HT2A agonist designer drug

Context. Abuse of synthetic stimulant compounds resulting in significant toxicity is being increasingly reported by poison centers. Toxicologic assessment is complicated by inconsistent manufacturing processes and limited laboratory testing. We describe a case of self-reported exposure to 25-I (25I-NBOMe), a novel phenethylamine derivative, with subsequent quantification in serum. Case details. An 18-year-old male presented to the emergency department (ED) with severe agitation and hallucinations after jumping out of a moving car. He was tachycardiac (150–160 bpm) and hypertensive (150–170 mm Hg systolic and 110 mg Hg diastolic), and required physical restraints and treatment with intravenous lorazepam administration. His symptoms gradually improved and vital signs returned to normal over 48 h, though he continued to have episodes of aggressiveness. An assay was developed by our analytical toxicology laboratory for 25-I, and serum obtained during ED evaluation and treatment was found to contain 0.76 ng/ml of 25-I. Case discussion. For 25I-NBOMe, 25-I is a common abbreviation for 25I-NBOMe, which is a (n-benzyl) phenethylamine in the 2C “family.”Initially synthesized for research, cases of self-reported use of 25-I have recently appeared in the literature, some of which contain qualitative urine confirmation. There are no commercially available quantitative assays, and no previous reports have published serum concentrations. 25-I is a potent new synthetic drug with apparent significant behavioral toxicity that can be detected and quantified in serum.

Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death

We present a traumatic fatality of a 19-year-old man who had ingested blotter paper containing 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine]. Postmortem specimens were analyzed by high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Toxicology findings for fluids based upon blood or urine calibrators were as follows: peripheral blood, 405 pg/mL; heart blood, 410 pg/mL; urine, 2.86 ng/mL; and vitreous humor, 99 pg/mL. While findings based upon the method of standard additions were: gastric contents, 7.1 μg total; bile, 10.9 ng/g; brain, 2.54 ng/g and liver, 7.2 ng/g. To our knowledge the presented case is the first postmortem case of 25I-NBOMe intoxication documented by toxicological analysis of tissues and body fluids.

Determination of 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe) in serum and urine by high performance liquid chromatography with tandem mass spectrometry in a case of severe intoxication

We present a case of 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe), an N-benzyl phenethylamines derivative, intoxication and a high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method for detection and quantification of 25B-NBOMe. A 19-year-old male was found unresponsive with generalized grand mal seizure activity. On the second day of hospitalization, a friend admitted that the patient used some unknown drug called 25B. Serum and urine collected were sent to the Virginia Commonwealth University Medical Center Toxicology Laboratory for analysis. An HPLC-MS/MS method for the identification and quantification of 25B-NBOMe using 2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25H-NBOMe) as the internal standard (ISTD) was developed. As this is a novel, single-case presentation, an assay validation was performed prior to testing to ensure the reliability of the analytical results. The serum and urine specimens were determined to contain 180 pg/ml and1900 pg/ml of 25B-NBOMe, respectively.

Drinking water exposure to cadmium, an environmental contaminant, results in the exacerbation of autoimmune disease in the murine model.

Cadmium is a pervasive environmental contaminant. The primary route of exposure to the general population occurs via contaminated drinking water or food supplies. Our hypothesis was that cadmium could be a trigger for inducing autoimmune disease (AD) in genetically predisposed populations. Therefore, New Zealand Black/White F1 (NZBW) mice were exposed to cadmium via drinking water. Mice were exposed to: 0, 3, 30, 3000 or 10000 parts per billion (ppb) of cadmium in tap water for 2, 4, 28, or 31 weeks. After 4 weeks of exposure, in the group of mice exposed to 10000 ppb cadmium, there was an increased incidence of antinuclear antibodies (ANA). There was also deposition of immune complexes in all groups after 4 weeks of exposure. After 31 weeks, there were increases in IgG2a in mice exposed to low doses of cadmium. In an attempt to establish the progression from an autoimmune reaction to the development of AD, the biological marker for AD, proteinuria, was assessed. Onset of proteinuria was exacerbated by 11 weeks in mice exposed to cadmium. This data suggests that short-term exposure may result in a type of autoimmune reaction since the mice are beginning to produce ANA after only 4 weeks of exposure and there is immune-complex deposition in the kidney. Long-term exposure to cadmium appears to result in the exacerbation of AD as indicated by the development of proteinuria and continued presence of immune complexes in the kidney. The mechanism may involve the increased production of IgG2a, which is capable of forming immune complexes and causing autoimmune glomerulonephritis.

Inhalation exposure to smoke from synthetic “marijuana” produces potent cannabimimetic effects in mice

BACKGROUNDnUse of synthetic marijuana has increased in recent years, produced adverse effects and prompted the temporary DEA ban of five specific cannabinoid analogs, including JWH-018. The objectives of the current study include determining the chemical content of the herbal product, Buzz, assessing its behavioral effects upon inhalation exposure to mice, determining whether CB(1) receptors mediate its pharmacological activity, and ascertaining its biodisposition in blood and various organs.nnnMETHODSnUsing a nose-only exposure system, mice were exposed to smoke produced from combustion of an herbal incense product, Buzz, which contained 5.4% JWH-018. Cannabimimetic effects following smoke exposure were evaluated using the tetrad procedure, consisting of the following indices: hypomotility, antinociception, catalepsy, and hypothermia. Additionally, blood and tissues were collected for JWH-018 quantification.nnnRESULTSnInhalation exposure to Buzz produced dose-related tetrad effects similar to marijuana as well as dose-related increased levels of JWH-018 in the blood, brain, heart, kidney, liver, lung, and spleen. The behavioral effects were blocked by rimonabant, a CB(1) receptor antagonist. Effects produced by Buzz were similar in magnitude and time-course to those produced by marijuana, though equipotent doses of Buzz and marijuana yielded considerably lower brain levels of JWH-018 than THC for the respective materials.nnnCONCLUSIONSnInhalation exposure to a product containing JWH-018 penetrates into the brain and other organs and produces CB(1) receptor-mediated behavioral pharmacological effects in mice. The increased potency of JWH-018 compared to THC, the variable amount of drug added to various herbal products, and unknown toxicity, undoubtedly contribute to public health risks of synthetic cannabinoids.

Toxicities Associated With NBOMe Ingestion—A Novel Class of Potent Hallucinogens: A Review of the Literature

BACKGROUNDnA new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse.nnnOBJECTIVEnOur aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion.nnnMETHODSnWe searched PubMed for relevant English-language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted.nnnRESULTSnA total of 10 citations met the criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analogue identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Of all the patients, 7 (35%) were discharged after a period of observation, whereas 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common abnormalities reported on laboratory tests were elevated level of creatinine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%).nnnCONCLUSIONnNBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens.

Postmortem tissue distribution of acetyl fentanyl, fentanyl and their respective nor-metabolites analyzed by ultrahigh performance liquid chromatography with tandem mass spectrometry

In the last two years, an epidemic of fatal narcotic overdose cases has occurred in the Tampa area of Florida. Fourteen of these deaths involved fentanyl and/or the new designer drug, acetyl fentanyl. Victim demographics, case histories, toxicology findings and causes and manners of death, as well as, disposition of fentanyl derivatives and their nor-metabolites in postmortem heart blood, peripheral blood, bile, brain, liver, urine and vitreous humor are presented. In the cases involving only acetyl fentanyl (without fentanyl, n=4), the average peripheral blood acetyl fentanyl concentration was 0.467 mg/L (range 0.31 to 0.60 mg/L) and average acetyl norfentanyl concentration was 0.053 mg/L (range 0.002 to 0.086 mg/L). In the cases involving fentanyl (without acetyl fentanyl, n=7), the average peripheral blood fentanyl concentration was 0.012 mg/L (range 0.004 to 0.027 mg/L) and average norfentanyl blood concentration was 0.001 mg/L (range 0.0002 to 0.003 mg/L). In the cases involving both acetyl fentanyl and fentanyl (n=3), the average peripheral blood acetyl fentanyl concentration was 0.008 mg/L (range 0.006 to 0.012 mg/L), the average peripheral blood acetyl norfentanyl concentration was 0.001 mg/L (range 0.001 to 0.002 mg/L), the average peripheral blood fentanyl concentration was 0.018 mg/L (range 0.015 to 0.021mg/L) and the average peripheral blood norfentanyl concentration was 0.002 mg/L (range 0.001 mg/L to 0.003 mg/L). Based on the toxicology results, it is evident that when fentanyl and/or acetyl fentanyl were present, they contributed to the cause of death. A novel ultrahigh performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) method to identify and quantify acetyl fentanyl, acetyl norfentanyl, fentanyl and norfentanyl in postmortem fluids and tissues is also presented.

High-performance liquid chromatography tandem mass spectrometry method for the determination of 2CC-NBOMe and 25I-NBOMe in human serum.

2CC-NBOMe {4-chloro-2,5-dimethoxyphenethyl-N-[(2-methoxyphenyl) methyl] ethanamine} and 25I-NBOMe {2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl] ethanamine} are of a class of N-benzyl phenethylamine derivatives whose synthesis was first reported in the scientific literature in 2011. Recent reports from personal drug experience websites and in the popular press indicate these drugs are the latest in a series of designer Bath Salt drugs of abuse. The presented high-performance liquid chromatography triple quadrupole mass spectrometry (HPLC/MS/MS) method was developed for the detection and quantification of 2CC-NBOMe and 25I-NBOMe in serum of intoxicated emergency department patients. The assay applies 2-u200b(2,u200b5-u200bdimethoxyphenyl)-u200bN-u200b(2-u200bmethoxybenzyl) ethanamine (25H-NBOMe) as the internal standard. Samples were extracted using solid-phase extraction columns. The chromatographic separation was performed on a Luna 3 µ C8(2) 100 Å, 100 × 2.0 mm, column. Detection was accomplished by multiple-reaction monitoring via an electrospray ionization source operating in the positive ionization mode. The calibration curves were linear over the investigated concentration range, 30-2000 pg/mL, with a lower limit of detection of 10 pg/mL for both 2CC-NBOMe and 25I-NBOMe. The method proved suitable for serum clinical toxicology testing. Two severely intoxicated emergency department patients were determined to have serum concentrations of 250 and 2780 pg/mL of 25I-NBOMe using the presented method.

Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2-Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper

In recent years, N-methoxybenzyl-methoxyphenylethylamine (NBOMe) derivatives, a class of designer hallucinogenic drugs, have become popular drugs of abuse. These drugs have been the cause of severe intoxications and even deaths. They act as 5-HT2A receptors agonists and have been reported to produce serotonin-like syndrome with bizarre behavior, severe agitation and seizures persisting for as long as 3 days. The most commonly reported derivatives are 25I-NBOMe, 25B-NBOMe and 25C-NBOMe, respectively 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl]ethanamine, N-(2-methoxybenzyl)-2,5-dimethoxy-4-bromophenethylamine and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine. Like many low dose hallucinogenic drugs these compounds are often sold on blotter paper. Three different types of commercially available blotter papers reported to contain NBOMe derivatives were obtained. These blotter papers were screened using Direct Analysis in Real Time AccuTOF(TM) mass spectrometry followed by confirmation and quantification by high-performance liquid chromatography triple quadrapole mass spectrometry. The major drug present on each of the three blotter products was different, 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The blotter papers were also found to have minute amounts of two or three NBOMe derivative impurities of 25H-NBOMe, 25I-NBOMe, 25C-NBOMe, 25B-NBOMe and/or 25D-NBOMe.

“My Friend Said it was Good LSD”: A Suicide Attempt Following Analytically Confirmed 25I-NBOMe Ingestion

Abstract A new class of synthetic hallucinogens called NBOMe has emerged, and reports of adverse effects are beginning to appear. We report on a case of a suicide attempt after LSD ingestion which was analytically determined to be 25I-NBOMe instead. Clinicians need to have a high index of suspicion for possible NBOMe ingestion in patients reporting the recent use of LSD or other hallucinogens.