Editors' ChoicePharmacology

Real life zombie apocalypse in New York City

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Science Translational Medicine  01 Feb 2017:
Vol. 9, Issue 375, eaam6048
DOI: 10.1126/scitranslmed.aam6048

Abstract

Synthetic cannabinoid use elicits “zombie-like” symptoms in New York.

Plant-derived compounds have been used by even our most ancient of ancestors for medicinal purposes. Since William O’Shaughnessy originally introduced it to Western society in the 19th century, marijuana (Cannabis sativa) has been used to treat a plethora of ailments, including pain, epilepsy, arthritis, and poor appetite. A breakthrough in our understanding of how marijuana elicits such diverse effects came when Gaoni and Mechoulam isolated and described the structure of Δ9-tetrahydrocannabinol (Δ9-THC), the active ingredient in cannabis. It was later found that this “phytocannabinoid” Δ9-THC elicited most of its biological effects by binding to two separate G protein–coupled receptors known as cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Given the potent psychoactive and therapeutic effects of the phytocannabinoid Δ9-THC, there have been concerted efforts by academic and pharmaceutical chemists to generate a number of synthetic cannabinoid receptor agonists, with varying CB1 and CB2 receptor activity.

Unfortunately, the good intentions of these chemists have gone bad in the streets of New York City. Now, Adams et al. report “zombie-like” effects of the herbal product “AK-47 24 Karat Gold” and trace the characteristic groaning and slow mechanical movements of the arms and legs to the synthetic cannabinoid methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA). AMB-FUBINACA is estimated to be 85 times as potent as Δ9-THC in activating CB1, which potentially explains the “zombie-like” effects.

On 12 July 2016, emergency responders were dispatched to the borough of Brooklyn, New York, to confront at least 33 individuals who were exhibiting “zombie-like” symptoms, including groaning and an eerie blank stare. Adams et al. obtained blood and urine samples from eight of the affected individuals and, using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), identified a metabolite of the synthetic cannabinoid AMB-FUBINACA as the likely culprit for these physiological effects. In an impressive collaboration between first responders, law enforcement, and analytical scientists, the work by Adams et al. was able to identify the active compound in only 17 days. This work highlights the obvious dangers of synthetic cannabinoids and illicit drug use and provides a scientific explanation for the recent “zombie” outbreak in New York.

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