The potency of the synthetic cannabinoid identified in these analyses is consistent with strong depressant effects that account for the "zombielike" behavior reported in this mass intoxication. AMB-FUBINACA is an example of the emerging class of "ultrapotent" synthetic cannabinoids and poses a public health concern. Collaboration among clinical laboratory staff, health professionals, and law enforcement agencies facilitated the timely identification of the compound and allowed health authorities to take appropriate action.

Synthetic cannabinoid receptor agonists (SCRAs) are a dynamic class of new psychoactive substances (NPS), with novel chemotypes emerging each year. Following the putative detection of 5F-CUMYL-P7AICA in Australia in 2016, the scaffold-hopping SCRAs 5F-CUMYL-PICA, 5F-CUMYL-PINACA, and 5F-CUMYL-P7AICA were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). Since little is known of the pharmacology of 7-azaindole SCRAs like 5F-CUMYL-P7AICA, the binding affinities and functional activities of all compounds at cannabinoid type 1 and type 2 receptors (CB and CB , respectively) were assessed using tritiated radioligand competition experiments and fluorescence-based plate reader membrane potential assays. Despite CB binding affinities differing by over two orders of magnitude (K = 2.95-174 nM), all compounds were potent and efficacious CB agonists (EC = 0.43-4.7 nM), with consistent rank order for binding and functional activity (5F-CUMYL-PINACA >5F-CUMYL-PICA >5F-CUMYL-P7AICA). Additionally, 5F-CUMYL-P7AICA was found to exert potent cannabimimetic effects in mice, inducing hypothermia (6°C, 3 mg/kg) through a CB -dependent mechanism.

Objective: The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/ acetaminophen.Methods: Over an 8-day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their "normal dose" of hydrocodone/ acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills.Results: One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag-valve-mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26-39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600-6,900 lg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units. Conclusions:A serious outbreak of exaggerated opioid toxicity caused by fentanyl-adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law enforcement, and healthcare facilities and resources.

5F‐PY‐PICA and 5F‐PY‐PINACA are pyrrolidinyl 1‐(5‐fluoropentyl)ind (az)ole‐3‐carboxamides identified in 2015 as putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS). 5F‐PY‐PICA, 5F‐PY‐PINACA, and analogs featuring variation of the 1‐alkyl substituent or contraction, expansion, or scission of the pyrrolidine ring were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–quadrupole time‐of‐flight–mass spectrometry (LC–QTOF–MS). In competitive binding experiments against HEK293 cells expressing human cannabinoid receptor type 1 (hCB1) or type 2 (hCB2), all analogs showed minimal affinity for CB1 (pKi < 5), although several demonstrated moderate CB2 binding (pKi 5.45–6.99). In fluorescence‐based membrane potential assays using AtT20‐hCB1 or ‐hCB2 cells, none of the compounds (at 10 μM) produced an effect >50% of the classical cannabinoid agonist CP55,940 (at 1 μM) at hCB1, although several showed slightly higher relative efficacy at hCB2. Expansion of the pyrrolidine ring of 5F‐PY‐PICA to an azepane (8) conferred the greatest hCB2 affinity (pKi 6.99) and activity (pEC50 7.54, Emax 72%) within the series. Unlike other SCRA NPS evaluated in vivo using radio biotelemetry, 5F‐PY‐PICA and 5F‐PY‐PINACA did not produce cannabimimetic effects (hypothermia, bradycardia) in mice at doses up to 10 mg/kg.

Background Use of new psychoactive substances (NPS) has increased over the last decade. During this period, variability of both clinical presentations and chemical compositions of these compounds has increased. Synthetic cannabinoids (SCs) are the most commonly used NPS and there are more than 100 documented unique molecules in this class. “Black Mamba”, often associated to ADB-FUBINACA, is the most commonly used SC in Colorado. It has been linked to kidney injury, myocardial toxicity, seizures, and death. Objectives We aim to identify the chemical constituents and quantification of eight cases of reported “Black Mamba” use in order to further understand the clinical variability in patients presenting for emergency stabilization. Methods We report data from eight cases of reported “Black Mamba” use prospectively captured through the Colorado site of the Psychoactive Surveilance Consortium and Analysis Network (P SCAN). P SCAN is a geographically representative group of academic hospitals that capture clinical presentation, outcome, and biologic samples from patients that present for emergency stabilization following NPS use. Serum and urine samples were analyzed and quantified by liquid chromatography-quadrupole time-of-flight mass spectrometry after a qualitative screen for over 600 unique NPS compounds. Results In the reported eight cases, the median age was 28 years old. There were four male and four females. Four patients had agitation/delirium and four patients had chest pain. Normal saline, benzodiazepines and ondansetron were the common treatment provided in the emergency department (ED). Two patients were discharged from the ED and six patients being admitted for emergency observation with a median length of stay (LOS) of six hours. No deaths were reported. Confirmatory testing revealed that only five patients (62.5%) had SCs found in blood or urine samples. Cocaine, NRG-3, 3-methoxyphencyclidine hydrochloride (MeO-PCP), and methamfetamine were identified in other presentations. Conclusions The wide range of clinical presentations from “Black Mamba” use may be explained by the wide variability of chemical constituents found by laboratory analysis.

Background and aims The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year . Design Observational study involving patient records and biological samples. Setting Seven academic emergency medical centers across the United States. Participants ED patients (n = 127) > 8 years of age with possible NPS use who were identified and enrolled in PSCAN by clinical providers or research personnel. Measurements Clinical signs, symptoms and treatments were abstracted from the patients' health records. Biological samples were collected from leftover urine, serum and whole blood. Biological and drug samples, when available, were tested for drugs and drug metabolites via liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Findings Patients in whom synthetic opioids were detected (n = 9) showed higher rates of intubation (four of nine), impaired mental status (four of nine) and respiratory acidosis (five of nine) compared with the rest of the cohort (nine of 118, P-value < 0.05). Patients in whom synthetic cannabinoid (SC) were found (n = 27) had lower median diastolic blood pressures (70.5 versus 77 mmHg, P = 0.046) compared with the rest of the cohort. In 64 cases of single drug ingestion, benzodiazepines were administered in 25 cases and considered effective by the treating physician in 21 (84%) cases. Conclusions During its first year of operation, the Psychoactive Surveillance Consortium and Analysis Network captured clinical data on new classes of drugs paired with biological samples over a large geographical area in the United States. Synthetic cannabinoids were the most common new psychoactive drug identified. Synthetic opioids were associated with a high rate of intubation and respiratory acidosis.

High-latitude terrestrial ecosystems face the triple threats of climate warming, increased exposure to UV arising from polar ozone depletion, and deforestation. Lichen communities of southernmost Chile are recognized for their high diversity, which includes nitrogen-fixing cyanolichens. Such lichens are common on forest trees, contribute nitrogen to forests, and are sensitive to exposure following deforestation (widespread in this region). In a pilot study of exposure effects on tree lichens, using nondestructive imaging methods, we compared lichen communities on trunks of isolated vs. forest tree trunks of southern Chilean beech (Nothofagus dombeyi, Nothofagaceae). We chose trees of similar diameter and trunk lean angle in conserved forest and nearby logged meadow on Navarino Island, XII Region Magallanes and Chilean Antarctica, Chile, within the annual southern ozone hole. Ninety-five percent of cyanolichen records, including Nephroma antarcticum, and 66% of records for other foliose lichens were from the forest, whereas pendulous usneoid lichens dominated N. dombeyi bark at the meadow site. Limitation of cyanolichen growth on isolated trees could affect ecosystem function in this poorly studied habitat. Possible factors contributing to strong community differences were increased light intensity, UV radiation, and wind stress, plus limited ability of lichens to colonize isolated trees in the logged meadow. UV radiation was likely an important stressor for some lichen species but not others. We recommend more extensive monitoring to pinpoint causes of differing lichen communities, and we encourage better protection of bark-dwelling lichens in southern hemisphere regions facing multiple threats.

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