Genes explain the effects of psychedelic drugs

By The Science Advisory Board staff writers

July 28, 2022 -- Not everyone has the same response to psychedelic drugs and North Carolina researchers have figured out why -- seven genetic variants of one serotonin receptor greatly impact a certain serotonin receptor’s structure and function.

In their in vitro study, researchers at the University of North Carolina, Chapel Hill studied the effect of four psychedelic drugs, psilocybin, lysergic acid diethylamide (LSD), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and mescaline, on the serotonin receptor 5-HT2A, which is responsible for mediating the effects of psychedelic drugs (ACS Chemical Neuroscience, July 27, 2022).

They used a series of assays to measure the effect that seven different single nucleotide polymorphisms (SNPs) had on in vitro binding and signaling of the 5-HT2A serotonin receptor when in the presence of the four classical psychedelics. They found some gene variations, even ones at a distance from the binding site, alter the way the receptor interacts with the psychedelic drugs. For instance, the SNP Ala230Th had both increased and reduced responses to the drugs tested compared with the original version of the gene, whereas the His452Th mutation showed only reduced effects.

The results indicate patients with different genetic variations will react differently to psychedelic drugs and the researchers suggest physicians consider the genetics of a patient's serotonin receptors to identify which psychedelic compound is likely to be the most effective treatment.

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