Thermolytic Degradation of Synthetic Cannabinoids: Chemical Exposures and Pharmacological Consequences
| Autor: | Thomas F. Gamage, Ricardo A. Cortes, Gerald T. Pollard, Julie A. Marusich, Jenny L. Wiley, Brian F. Thomas, Megan Grabenauer, Richard C. Kevin, Timothy W. Lefever, Alexander L. Kovach, Purvi R. Patel, Anderson Cox |
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| Rok vydání: | 2016 |
| Předmět: |
Drug
Male Cannabinoid receptor Hot Temperature Indoles medicine.drug_class media_common.quotation_subject medicine.medical_treatment Naphthalenes 01 natural sciences Designer Drugs Receptor Cannabinoid CB2 03 medical and health sciences Mice 0302 clinical medicine Neuropharmacology Receptor Cannabinoid CB1 Synthetic cannabinoids medicine Cannabinoid receptor type 2 Organic chemistry Animals Humans Dronabinol media_common Pharmacology Indole test Mice Inbred ICR Dose-Response Relationship Drug Chemistry Cannabinoids 010401 analytical chemistry Biological activity 0104 chemical sciences Designer drug Mice Inbred C57BL HEK293 Cells Molecular Medicine Cannabinoid Erratum 030217 neurology & neurosurgery medicine.drug Protein Binding |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 361(1) |
| ISSN: | 1521-0103 |
| Popis: | 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. Here, we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds. Moreover, these degradants were formed under conditions simulating smoking. Some products of combustion retained high affinity at the cannabinoid 1 (CB1) and CB2 receptors, were more efficacious than (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940) in stimulating CB1 receptor-mediated guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding, and were potent in producing Δ9-tetrahydrocannabinol-like effects 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. |
| Databáze: | OpenAIRE |
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