UNC research finds genetic variants in the 5-HT2A serotonin receptor may shape responses to psychedelic therapy

UNC School of Medicine researchers led by Bryan Roth report that genetic variation in the 5-HT2A serotonin receptor may help explain why patients respond differently to psychedelic-assisted treatments. In cell-based laboratory assays, seven naturally occurring single nucleotide polymorphisms altered receptor binding or signaling in response to four psychedelic compounds: psilocin, LSD, 5-MeO-DMT, and mescaline. Some variants affected responses even when they were located far from the drug-binding site. For example, Ala230Th showed a decreased response to psilocin, the active metabolite of psilocybin, while Ala447Val reduced effects for two compounds. The findings suggest that patients' receptor genetics could eventually help guide compound selection in clinical trials, but the study was conducted in vitro and does not yet establish treatment outcomes in people.