Study Finds Genetic Link to Effects of Psychedelics

According to a recently published study by University of North Carolina researchers, common genetic variations in a particular serotonin receptor could be responsible for the different effects that psychedelics have on different individuals. The study, which comes at a time of reinvigorated research into the potential therapeutic benefits of psychedelics, may shed light on why the substances appear to have dramatically beneficial effects in some patients with severe mental illness, while others see the drugs as having little therapeutic value during the meal .

Bryan Roth, MD, PhD, led a research team at the University of North Carolina (UNC) to complete the study. The aim of the research was to examine how variations in this one serotonin receptor alter the activity of four psychedelic therapies. Laboratory research in cells showed that seven variants uniquely and differentially affect the receptor’s response to four psychedelic drugs – psilocin, LSD, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline. Researchers believe the in vitro research could be useful in determining appropriate therapies for patients’ mental health.

“Based on our study, we expect that patients with different genetic variations will respond differently to psychedelic-assisted treatments,” said Roth, who directs the National Institutes of Health’s Psychotropic Drug Screening Program. “We think that physicians should consider the genetics of a patient’s serotonin receptors to determine which psychedelic compound is likely to be the most effective treatment in future clinical trials.”

Psychedelics and Mental Health

A 2020 study published in the journal JAMA Psychiatry found that psilocybin-assisted psychotherapy was a fast-acting and effective treatment for a group of 24 participants with major depressive disorders. A separate study published in 2016 found that treatment with psilocybin resulted in significant and sustained decreases in depression and anxiety in patients with life-threatening cancer. And last year, researchers found that psychedelic users experienced less stress during the lockdowns put in place to control the COVID-19 pandemic.

Previous research has also found that psychedelics stimulate serotonin receptors in the brain. The 5-hydroxytryptamine receptor, also known as 5-HT2A, is responsible for mediating how a person responds to psychedelics. However, there are several naturally occurring, random genetic variations that can affect the function and structure of the 5-HT2A receptor. Much of the research on the effects of psychedelics on mental health is inspired by the drugs’ effects on serotonin receptors, which bind the neurotransmitter serotonin and other similar molecules to help regulate mood, emotions, and appetite.

While showing great promise, psychedelics do not appear to be an effective treatment for everyone. Dustin Hines, PhD, an assistant professor of neuroscience in the Department of Psychology at the University of Nevada, Las Vegas, who was not involved in the UNC study, said the research may shed light on why psychedelic therapies work well for some patients, while others find little therapeutic benefit from the drugs.

“Genetic variations in this receptor have been shown to affect how patients respond to other drugs,” Hines told Healthline. “While psychedelic therapies can provide rapid and sustained therapeutic benefits for multiple mental health problems, there is a subset of patients who do not respond.”

Hines also noted that individual-to-individual differences in mental health conditions could also contribute to how well patients respond to both psychedelic and more traditional treatments.

“Some people with depression may have a genetic makeup that makes them more likely to have depression in their lifetime,” Hines said. “Other individuals who are dealing with depression may have more situational or environmental contributions.”

UNC researchers noted that the study could provide insight to clinicians considering psychedelics as a treatment for their patients and called for further investigation.

“This is another piece of the puzzle that we need to be aware of when deciding to prescribe a therapeutic with such dramatic effects alongside the therapeutic effect,” Roth said. “Further research will help us continue to find the best ways to help individual patients.”

The results of the study were published last week in the journal ACS Chemical Neuroscience.