Metabolism and Toxicological Analysis of Synthetic Cannabinoids in Biological Fluids and Tissues

Headnote

REFERENCE: Presley BC, Gurney SMR, Scott KS, Kacinko SL, Logan BK: Metabolism and toxicological analysis of synthetic cannabinoids in biological fluids and tissues; Forensic Sci Rev 28:103; 2016.

ABSTRACT: Synthetic cannabinoids, which began proliferating in the United States in 2009, have gone through numerous iterations of modification to their chemical structures. More recent generations of compounds have been associated with significant adverse outcomes following use, including cognitive and psychomotor impairment, seizures, psychosis, tissue injury and death. These effects increase the urgency for forensic and public health laboratories to develop methods for the detection and identification of novel substances, and apply these to the determination of their metabolism and disposition in biological samples. This comprehensive review describes the history of the appearance of the drugs in the United States, discusses the naming conventions emerging to designate new structures, and describes the most prominent new compounds linked to the adverse effects now associated with their use. We review in depth the metabolic pathways that have been elucidated for the major members of each of the prevalent synthetic cannabinoid drug subclasses, the enzyme systems responsible for their metabolism, and the use of in silico approaches to assist in predicting and identifying the metabolites of novel compounds and drug subclasses that will continue to appear. Finally, we review and critique analytical methods applied to the detection of the drugs and their metabolites, including immunoassay screening, and liquid chromatography mass spectrometry confirmatory techniques applied to urine, serum, whole blood, oral fluid, hair, and tissues.

KEYWORDS: Designer drugs, drug metabolism and disposition, synthetic cannabinoids, synthetic drug scheduling, toxicological analysis.

Introduction

Initially thought to be a temporary distraction and a novelty, synthetic cannabinoid use in the United States and internationally has grown and diversified over the last seven years to become a discrete and challenging part of the recreational drug use market. The diversity of members of this drug class has expanded rapidly, with over 130 different chemical substances in this class being tracked by the European Monitoring Center for Drugs and DrugAddiction (EMCDDA) [39]. In the United States, the National Forensic Laboratory Information System (NFLIS) continues to report increases in the numbers of synthetic cannabinoid cases submitted to crime laboratories for analysis, with almost half the of most common...