Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugs

S. M. R. Gurney1, K. S. Scott2, S. L. Kacinko3, B. C. Presley3,4, B. K. Logan3,5,*

1Drexel University, Department of Biology, Philadelphia, Pennsylvania, United States of America; 2Arcadia University, Forensic Science, Glenside, Pennsylvania, United States of America; 3NMS Labs, Willow Grove, Pennsylvania, United States of America; 4Temple University, Department of Chemistry, Philadelphia, Pennsylvania, United States of America; 5Center for Forensic Science Research and Education, Fredric Rieders Family Renaissance Foundation, Willow Grove, Pennsylvania, United States of America

The article Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugsappears in the Forensic Science Review 26:53; 01/2014. Abstract is included below.

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ABSTRACT: Synthetic cannabinoid drugs have become an established part of the recreational drug landscape in the United States and internationally. These drugs are manufactured in clandestine laboratories internationally and distributed in the United States in smoking mixtures, use of which produces effects very similar to use of marijuana. The adverse-effect profile of the drugs has not been studied in humans and infrequently in animal models, so much of the information about their toxicity comes from emergency department and treatment reports and forensic case studies. This review considers the discovery and characterization of the endocannabinoid system, approaches to receptor-binding studies of various synthetic cannabinoids from the first wave of naphthoylindoles (e.g., JWH-018) to the emerging adamantoylindole drugs (e.g., AKB-48), and their analogues, to evaluate the potential activity of drugs in this class. Currently employed approaches to assessing functional activity of the drugs using in vitro and in vivo models is also described, and comparisons made to the effects of THC. The physiological effects of activation of the endocannabinoid system in humans are reviewed, and the physiological effects of cannabinoid use are described. Case reports of adverse events including emergency department admissions, mental health admissions, and clinical and forensic case reports are presented in detail and discussed to summarize the current state of knowledge of adverse effects, both clinical and forensic in humans, including effects on driving ability, and tissue injury and death. The greatest weight is accorded to those reports that include toxicological confirmation of use. Finally, we discuss the current status of attempts to schedule and control the distribution of synthetic cannabinoids and the relevance of receptor binding and functional activity in this context. There is growing toxicological and pharmacological evidence of impairment, psychosis, tissue injury, and isolated deaths attributable to this emerging class of drugs.

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