Pharmacologic analysis of non-synonymous coding 5-HT2A SNPs reveals alterations psychedelic drug potencies and efficacies

Serotonin (5-Hydroxytryptamine; 5-HT) 2A receptor (5-HT 2A R) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT 2A R affect the signaling of four commonly used psychedelic drugs. We examined the in vitro pharmacology of seven non-synonymous SNPs, which give rise to S12N, T25N, D48N, I197V, A230T, A447V, and H452Y variant 5-HT 2A serotonin receptors. We found that these non-synonymous SNPs exert statistically significant, although modest, effects on the efficacy and potency of four therapeutically relevant hallucinogens. Significantly, the in vitro pharmacological effects of the SNPs drug actions at 5-HT 2A R are drug specific. Table of Contents/Abstract Graphic