An outbreak of deaths associated with AMB-FUBINACA in Auckland NZ.

BACKGROUND: AMB-FUBINACA is a synthetic cannabinoid that has been associated with periodic outbreaks of acute poisonings, but few fatalities. In late May, June and July 2017 Auckland, New Zealand, experienced an outbreak of deaths associated with AMB-FUBINACA that continued at a rate of about 2-3 per month through February 2019. The aim of this study was to define the demographic, circumstantial, pathological and toxicological characteristics of this outbreak. METHODS: All records of the Northern Forensic Pathology Service, Auckland Hospital, were reviewed in which the word "AMB-FUBINACA" was referenced, including initial police reports, autopsy reports and toxicology reports. Recorded data included age, sex, race/ethnicity, times and locations, cause of death, autopsy and toxicology findings, and a brief summary of the circumstances of death. Descriptive statistics were performed using IBM® SPSS® Statistics Version 24 and Microsoft® Excel® Version 14.7.2. FINDINGS: Sixty-four cases were identified. One sudden infant death and five cases where cause of death was due to trauma were excluded. Of the remaining 58 cases, 88% were male. Mean age was 42 years. In 95% of the deaths, AMB-FUBINACA alone or in combination with alcohol or another drug was listed as the primary or contributory cause of death. In 41 cases postmortem blood concentrations of AMB-FUBINACA acid were available, ranging from <45 ng/mL to >1000 ng/mL, mean 229 ng/mL, median 140 ng/mL. Comorbidities identified included mixed intoxications (29%), heart disease (47%) and obesity (16%). A mental health diagnosis was reported in 50%, and 40% were on antipsychotic medications. INTERPRETATION: This study presents characteristics, comorbidities and toxicological findings in a unique outbreak of deaths associated with the synthetic cannabinoid AMB-FUBINACA in Auckland, NZ. FUNDING: All work was funded as part of the usual employment of the authors in their respective institutions. No special funding sources are reported.

Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.

Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.

Cerebral hypoxia-ischemia causes cardiac damage in a rat model.

Hypoxia-ischemia (HI) is a model of cerebral ischemia used to model neonatal hypoxia and to study brain damage. Interpreting the results of experiments that use HI rests partly on the assumption that only the brain suffers major damage. In this study, we demonstrate that HI also has adverse consequences on the heart. Both infarction scoring and measurements of troponin I indicate cardiac damage subsequent to HI. These results indicate that the effects of HI on the heart may confound the interpretation of experiments that have used HI to study neuroprotection or other aspects of brain damage.