View article

Synthetic cannabinoid receptor agonists (SCRAs) elicit many of their psychoactive effects via type‐1 human cannabinoid (CB₁) receptors. Enantiomer pairs of eight tert‐leucinate or valinate indole‐ and indazole‐3‐carboxamide SCRAs were synthesized and their CB₁ potency and efficacy assessed using an in vitro β‐arrestin recruitment assay in a HEK239T stable cell system. A chiral high‐performance liquid chromatography method with photodiode array and/or quadrupole time‐of‐flight‐mass spectrometry detection (HPLC‐PDA and HPLC‐PDA‐QToF‐MS) was applied to 177 SCRA‐infused paper samples seized in Scottish prisons between 2018 and 2020. In most samples, SCRAs were almost enantiopure (S)‐enantiomer (>98% of total chromatographic peak area), although in some (n = 18), 2% to 16% of the (R)‐enantiomer was detected. (S)‐enantiomers are consistently more potent than (R)‐enantiomers …