Thermolytic Degradation of Synthetic Cannabinoids: Chemical Exposures and Pharmacological Consequences

• NCJ Number: 252424
• Journal: Journal of Pharmacology and Experimental Therapeutics Volume: 361 Issue: 1 Dated: April 2017 Pages: 162-171
• Author(s): Brian F. Thomas; Timothy W. Lefever; Ricardo A. Cortes; Megan Grabenauer; Alexander L. Kovach; Anderson O. Cox; Purvi R. Patel; Gerald R. Pollard; Julie A. Manusich; Richard C. Kevin; Thomas F. Gamage; Jenny L. Wiley
• Date Published: April 2017
• Length: 10 pages
• Grant Number(s): 2012-R2-CX-K001
• Agencies: NIJ-Sponsored
• Publication Type: Research (Applied/Empirical); Report (Study/Research); Report (Grant Sponsored); Program/Project Description
• Award: Characterization of Designer Drugs: Chemical Stability, Exposure, and Metabolite Identification

Annotation

This study determined that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds, and these degradants were formed under conditions simulating smoking.

Abstract

Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal spice for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. The current study found that some products of combustion retained high affinity, were more efficacious, and were potent in laboratory animals; whereas, other compounds had low affinity and efficacy and were devoid of cannabimimetic activity. Degradants that retained affinity and efficacy also substituted in drug discrimination tests for the prototypical synthetic cannabinoid 1-pentyl-3-(1-naphthoyl)indole (JWH-018), and are likely to produce psychotropic effects in humans. Hence, it is important to take into consideration the actual chemical exposures that occur during use of synthetic cannabinoid formulations to better comprehend the relationships between dose and effect. (Publisher abstract modified)