Behavioral pharmacology of five novel synthetic cannabinoids

Newly emerging synthetic cannabinoid compounds continue to be found in the designer drug market. They are often targeted as a ‘legal high’ alternative to traditional cannabinoids via ‘darknet’ markets and their increased potency and efficacy are becoming a growing concern internationally. The purpose of this study was to determine whether 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA exhibited similar behavioral effects as Δ9-tetrahydrocannabinol (Δ9-THC). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Male Sprague-Dawley rats were trained to discriminate between intraperitoneal injections of Δ9-THC (3 mg/kg) and vehicle. Following successful training, substitution tests for 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA were conducted. All of the test compounds decreased locomotor activity. 4-CN-CUMYL-BUTINACA (ED50 = 0.26 mg/kg), 4F-MDMB-BINACA (ED50 = 0.019 mg/kg), 5F-CUMYL-P7AICA (ED50 = 0.13 mg/kg) and EMB-FUBINACA (ED50 = 0.13 mg/kg) each fully substituted for the discriminative stimulus effects of the training dose of Δ9-THC, whereas 5F-AEB produced only a maximum of 67% drug-appropriate responding at 0.5 mg/kg. Higher doses produced piloerection, exophthalmos and convulsions. 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-CUMYL-P7AICA and EMB-FUBINACA are likely to produce similar subjective effects in humans as those produced by abused synthetic cannabinoids, and may therefore share similar abuse liability. In contrast, 5F-AEB may have a reduced abuse liability given its weaker THC-like discriminative stimulus effects but maybe more dangerous due to the adverse effects observed at doses needed to produce discriminative stimulus effects.