Positive Allosteric Modulation of the 5-HT1A Receptor by Indole-Based Synthetic Cannabinoids Abused by Humans

@article{doi:10.1021/acschemneuro.0c00034,

title = {Positive Allosteric Modulation of the 5-HT1A Receptor by Indole-Based Synthetic Cannabinoids Abused by Humans},

author = {Hideaki Yano and Pramisha Adhikari and Sett Naing and Alexander F Hoffman and Michael H Baumann and Carl R Lupica and Lei Shi},

url = {https://pubmed.ncbi.nlm.nih.gov/32324370/},

doi = {10.1021/acschemneuro.0c00034},

year  = {2020},

date = {2020-01-01},

journal = {ACS Chemical Neuroscience},

volume = {11},

number = {10},

pages = {1400-1405},

abstract = {The nonmedical (i.e., recreational) misuse of synthetic cannabinoids (SCs) is a worldwide public health problem. When compared to cannabis, the misuse of SCs is associated with a higher incidence of serious adverse effects, suggesting the possible involvement of noncannabinoid sites of action. Here, we find that, unlike the phytocannabinoid Δ9-tetrahydrocannabinol, the indole-moiety containing SCs, AM2201 and JWH-018, act as positive allosteric modulators (PAMs) at the 5-HT1A receptor (5-HT1AR). This suggests that some biological effects of SCs might involve allosteric interactions with 5-HT1ARs. To test this hypothesis, we examined effects of AM2201 on 5-HT1AR agonist-activated G protein-coupled inwardly rectifying potassium channel currents in neurons in vitro and on the hypothermic response to 5-HT1AR stimulation in mice lacking the cannabinoid receptor 1. We found that both 5-HT1AR effects were potentiated by AM2201, suggesting that PAM activity at 5-HT1AR may represent a novel noncannabinoid receptor mechanism underlying the complex profile of effects for certain SCs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}