Ethylbromazolam, a new designer benzodiazepine, has emerged in Canada, the UK, Australia, and Germany, with increasing detections since November 2024 and a concurrent decrease in bromazolam detections, likely due to bromazolam's international control on December 3, 2024. Other designer benzodiazepines like desalkylgidazepam and clobromazolam have also increased. In vitro patch clamp assays show ethylbromazolam has similar activity at the GABA-A receptor as bromazolam, with EC50 values of 10.1 nM and 15.2 nM respectively, indicating comparable pharmacological activity and potential harm. Ongoing market monitoring is recommended.
Some new synthetic cannabinoid receptor agonists (SCRAs) also directly activate the serotonin 5-HT₂A receptor, which may contribute to unexpected psychiatric side effects. Many SCRAs with a valinamide or tert-leucinamide head moiety showed in vitro activity at the 5-HT₂A receptor at high concentrations. In mice, the compound AB-5′F-BUTINACA caused neurological changes, sensorimotor alteration, antinociception, hypothermia, reduced breath rate, and hypolocomotion. These effects were mediated by both CB₁ and 5-HT₂A receptors, as they were prevented by selective antagonists. The findings indicate potential risks of SCRA consumption that could exacerbate unexpected psychiatric conditions.