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Pharmaco‐toxicological effects of the novel third‐generation fluorinate synthetic cannabinoids, 5F‐ADBINACA , AB‐FUBINACA , and STS‐135 in mice. In vitro and in vivo studies

2017; Wiley; Volume: 32; Issue: 3 Linguagem: Inglês

10.1002/hup.2601

1099-1077

Isabella Canazza, Andrea Ossato, Fabrizio Vincenzi, Adolfo Gregori, Fabiana Di Rosa, Federica Nigro, Alessandro Rimessi, Paolo Pinton, Katia Varani, Pier Andrea Borea, Matteo Marti,

Forensic Toxicology and Drug Analysis

Introduction 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 are 3 novel third‐generation fluorinate synthetic cannabinoids that are illegally marketed as incense, herbal preparations, or research chemicals for their psychoactive cannabis‐like effects. Methods The present study aims at investigating the in vitro and in vivo pharmacological activity of 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 in male CD‐1 mice, comparing their in vivo effects with those caused by the administration of Δ 9 ‐THC and JWH‐018. In vitro competition binding experiments revealed a nanomolar affinity and potency of the 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 on mouse and human CB 1 and CB 2 receptors. Moreover, these synthetic cannabinoids induced neurotoxicity in murine neuro‐2a cells. Results In vivo studies showed that 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 induced hypothermia; increased pain threshold to both noxious mechanical and thermal stimuli; caused catalepsy; reduced motor activity; impaired sensorimotor responses (visual, acoustic, and tactile); caused seizures, myoclonia, and hyperreflexia; and promoted aggressiveness in mice. Behavioral and neurological effects were fully prevented by the selective CB 1 receptor antagonist/inverse agonist AM 251. Differently, the visual sensory response induced by STS‐135 was only partly prevented by the AM 251, suggesting a CB 1 ‐independent mechanism. Conclusions For the first time, the present study demonstrates the pharmaco‐toxicological effects induced by the administration of 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 in mice and suggests their possible detrimental effects on human health.