Common genetic variations in a particular serotonin receptor could be responsible for the varying effects psychedelic drugs have on different individuals, according to a recently published study from researchers at the University of North Carolina. The study, which comes at a time of reinvigorated research into the potential therapeutic benefits of psychedelic drugs, could shed light on why the substances seem to have dramatically positive effects for some patients with serious mental health conditions while others find little therapeutic value in the drugs .
Bryan Roth, MD, PhD, led a team of researchers at the University of North Carolina (UNC) to complete the study. The goal of the research was to explore how variations in this one serotonin receptor changes the activity of four psychedelic therapies. The laboratory research in cells showed 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. The researchers believe that the in vitro research could be useful for determining appropriate mental health therapies for patients.
“Based on our study, we expect that patients with different genetic variations will react differently to psychedelic-assisted treatments,” said Roth, who leads the National Institutes of Health Psychotropic Drug Screening Program. “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 and Mental Health
Research published in 2020 in the journal JAMA Psychiatry found that psilocybin-assisted psychotherapy was a quick-acting and effective treatment for a group of 24 participants with major depressive disorder. A separate study published in 2016 determined that psilocybin treatment produced substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. And last year, researchers determined that psychedelic users had less stress during lockdowns put in place to control the COVID-19 pandemic.
Prior research has also determined that psychedelic drugs stimulate serotonin receptors in the brain. The 5-hydroxytryptamine receptor, also known as 5-HT2A, is responsible for mediating how a person reacts to psychedelic drugs. 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 into the effect that psychedelics have on mental health is inspired by the effect the drugs have on serotonin receptors, which bind the neurotransmitter serotonin and other similar molecules to help regulate mood, emotions and appetite.
Although they show great promise, psychedelic drugs do not seem to be effective as a 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 could shed light on why psychedelic therapies work well for some patients while others find little therapeutic benefit from the drugs.
“Genetic variation in this receptor has been shown to influence the response of patients to other drugs,” Hines told Healthline. “While psychedelic therapies can provide rapid and sustained therapeutic benefits for multiple mental health concerns, there are a proportion of patients who fail to respond.”
Hines also noted that differences in mental health conditions from person to person could also contribute to how well patients respond to both psychedelic and more traditional treatments.
“Some individuals with depression may have a genetic predisposition that increases the likelihood that they will experience depression in their lives,” Hines said. “Other individuals facing depression may have more situational or environmental contributions.”
The researchers at UNC noted that the study could help provide insight to clinicians considering psychedelics as a treatment for their patients and called for further investigation.
“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.”
Results of the study were published last week in the journal ACS Chemical Neuroscience.