Research

Research reveals role of DNA on therapeutic effect of psychedelics

The research has been carried out at the UNC School of Medicine lab of Bryan Roth, MD, PhD.

Published

on

The UNC School of Medicine has found that variants in one serotonin receptor in neurons could be why some patients fare much better after psychedelic therapy than other patients.

New research is pointing to the potential efficacy of psychedelics for treating conditions such as depression, anxiety and addiction. However, there is sometimes a disparity in patient outcomes – with a number of patients not experiencing the therapeutic effects.

UNC School of Medicine researchers led by Bryan Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology, report that one reason for treatment disparity could be common genetic variations in one serotonin receptor.

Published in the journal ACS Chemical Neuroscience, the lab research in cells shows that seven variants uniquely and differentially impact the receptor’s response to four psychedelic drugs — psilocin, LSD, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline.

Roth, who leads the NIH Psychotropic Drug Screening Program, commented: “Based on our study, we expect that patients with different genetic variations will react differently to psychedelic-assisted treatments.

“We think physicians should consider the genetics of a patient’s serotonin receptors to identify which psychedelic compound is likely to be the most effective treatment in future clinical trials.”

Psychedelics stimulate serotonin receptors in the brain, which bind the neurotransmitter serotonin and other similar amine-containing molecules, helping regulate people’s mood and emotions, as well as their appetite. 

In particular, the 5-hydroxytryptamine receptor known as 5-HT2A is responsible for mediating how a person reacts to psychedelic drugs. However, there are several naturally occurring, random genetic variations, known as single nucleotide polymorphisms, or SNPs, that can affect the function and structure of the 5-HT2A receptor.

Roth and colleagues wanted to explore how variations in this one serotonin receptor changes the activity of four psychedelic therapies.

UNC Graduate student Gavin Schmitz and postdoctoral researchers Manish Jain, PhD, and Samuel Slocum, PhD, used a series of experimental assays to measure the effect that seven different SNPs had on in vitro binding and signalling of the 5-HT2A serotonin receptor when in the presence of one of the four drugs. 

The results indicated that some gene variations – even ones far from the exact location where the drug binds to the receptor – alter the way that the receptor interacts with the psychedelic drugs.

The SNP Ala230Th had decreased response to one of the four drugs (psilocin the active metabolite of psilocybin) while the Ala447Val mutation showed only reduced effects to two of the drugs.

“This is another piece of the puzzle we must know when deciding to prescribe any therapeutic with such dramatic effect aside from the therapeutic effect,” Roth said. “Further research will help us continue to find the best ways to help individual patients.”

The National Institutes of Health and the Defense Advanced Research Projects Agency (DARPA) funded the research.

[activecampaign form=52]

Click to comment

Trending

Exit mobile version