We are joined again by Dr. Asher Brandt, Professor of Biochemistry at the Saint Joseph University, Connecticut, specializing in psychedelic pharmacology. We discuss a recently published paper about how Single Nucleotide Polymorphisms, (SNPs, pronounced “snips”) might alter the pharmacological signaling of potentially therapeutic psychedelics.

SNPs are the most common type of genetic variation among people. Specifically, it’s a genomic variant at a single base position in the DNA, which can lead to a single point amino acid mutation in the subsequently synthesized protein.

In the study, the authors examined whether sequence variations in the 5-HT2A receptor gene affect the signaling of some of the most used psychedelic drugs such as LSD, mescalin, psilocybin. They examined the in vitro pharmacology of seven non-synonymous SNPs, which give rise to a variant of 5-HT2A serotonin receptors. What they found is that these non-synonymous SNPs exert statistically significant effects on not just the the efficacy but also the potency of four therapeutically relevant psychedelics.


What’s mind blowing, in our opinion, is that the in vitro pharmacological effects of the SNP drug actions at 5-HT2A receptor are both amino acid and drug specific.

References:

Schmitz et al. (2022). 5-HT2A SNPs Alter the Pharmacological Signaling of Potentially Therapeutic Psychedelics. ACS Chem. Neurosci. 2022, 13, 16, 2386–2398.

NCBI SNPs Database (dbSNP) url: https://www.ncbi.nlm.nih.gov/snp/