People respond differently to psychedelic drugs—genetics could be the reason


Cluster headaches, anxiety and depression can be debilitating for people living with these conditions. Psychedelic drugs have shown benefits as treatments for these conditions in clinical studies, but not for everyone. Now, in ACS Chemical Neuroscience, researchers report that one reason could be common genetic variations in one serotonin receptor. They found that seven variants uniquely and differentially impacted the receptor’s in vitro response to four psychedelic drugs—psilocin, LSD, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline.

Recently, there’s been renewed interest and research in using psychedelic compounds that stimulate serotonin receptors in the brain because of several promising results from clinical trials. These receptors bind serotonin (5-hydroxytryptamine; 5-HT) and other similar amine-containing molecules, helping regulate people’s mood, perceptions, cognition and emotions, as well as their appetite. In particular, the serotonin receptor known as 5-HT2A is responsible for mediating the effects of psychedelic drugs. However, there are several naturally occurring, random genetic variations, known as single nucleotide polymorphisms, that can impact the 5-HT2A receptor’s structure and function. So, Bryan Roth and colleagues wanted to explore how variations in the serotonin 5-HT2A receptor impact the in vitro activity of four psychedelic therapies.

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