Positive Allosteric Modulation of the 5-HT1A Receptor by Indole-Based Synthetic Cannabinoids Abused by Humans
ACS Chemical Neuroscience April 23, 2020 Hideaki Yano, Pramisha Adhikari, Sett Naing et al. 26 citations
Synthetic cannabinoids (SCs) like AM2201 and JWH-018, but not the phytocannabinoid Δ9-tetrahydrocannabinol, act as positive allosteric modulators (PAMs) at the 5-HT1A receptor, a noncannabinoid site. In vitro, AM2201 potentiated 5-HT1A agonist-activated G protein-coupled inwardly rectifying potassium channel currents in neurons. In mice lacking cannabinoid receptor 1, AM2201 also potentiated the hypothermic response to 5-HT1A receptor stimulation. These findings suggest that PAM activity at 5-HT1A receptors may be a novel noncannabinoid mechanism contributing to the adverse effects of certain synthetic cannabinoids.