Do Toxic Synthetic Cannabinoid Receptor Agonists Have Signature in Vitro Activity Profiles? A Case Study of AMB-FUBINACA

Recreational consumption of synthetic cannabinoid receptor agonists (SCRAs) is a growing crisis in public health, in many parts of the world. AMB-FUBINACA is a member of this class of drugs, and is responsible for a large proportion of SCRA-related toxicity both in New Zealand and internationally. Strikingly, little is currently known about the mechanisms by which SCRAs exert toxic effects – nor whether their activity through the CB1 cannabinoid receptor (the mediator of cannabinoid-related psychoactivity) are sufficient to explain clinical observations. The current study therefore set out to perform a basic molecular pharmacology characterization of AMB-FUBINACA (in comparison to traditional research cannabinoids CP55,940, WIN55,212-2, and Δ9-THC) in fundamental pathways of receptor activity, including cAMP inhibition, pERK activation, ability to drive CB1 internalization, and ability to induce translocation of β-arrestins 1 and -2. Activity pathways were then compared by Operational analysis, to indicat...