Your Genes Can Impact How Psychedelics Affect You, Scientists Discover

A person's individual genetic makeup may play an important role in how they respond to psychedelic therapy, according to a new study published in ACS Chemical Neuroscience.

Psychedelic therapy is currently undergoing a renaissance, thanks to hundreds of new studies confirming that these once-taboo drugs can effectively treat mental health issues more effectively than legal pharmaceuticals. Recent research has found that even a single dose of psilocybin can reduce symptoms of anxiety or depression for years, regrow neural connections, and enhance creative thinking. Other studies have found that LSD and other psychedelics can help reduce pain and help combat addiction, especially when combined with therapy.

But although most subjects in these experiments showed significant improvements in their symptoms, others did not receive any benefit from the therapy at all. These studies were unable to explain this individual variability in responses, but a team of researchers from the University of North Carolina School of Medicine believe they might have found an explanation.

Psychedelics like LSD and psilocybin work by stimulating serotonin receptors in the brain, especially the receptor known as 5-HT2A. Serotonin is a neurotransmitter that helps regulate a person's mood, emotions, and appetite, and low levels of this natural compound have been associated with depression and other mental health issues. 

Serotonin receptors can vary from person to person, though, based on individual genetics. Random sequence variations in genes known as single-nucleotide polymorphisms (SNPs, pronounced like "snips") can affect the function and structure of 5-HT2A receptors, which means some people end up having slightly different serotonin receptors than others. Researchers have also learned that people with certain SNP variations have atypical responses to common antipsychotic medications.

The UNC team suspected these same genetic differences may also influence the effectiveness of psychedelic therapy. To test their theory, researchers recreated seven different common 5-HT2A receptor SNP variations in the lab. These in vitro cells were then exposed to mescaline, LSD, 5-MeO-DMT, and psilocin (the compound psilocybin breaks down into after it's ingested — and actually makes people trip). 

As expected, some of the genetic variations reacted differently to some of the psychedelics. For example, one of the SNP variants had a decreased response to two of the four psychedelics tested, and another had a weak response to psilocin, but worked fine with the other three drugs. Interestingly, some of these variations even altered receptors' interaction with psychedelics even if they were located far away from the exact location where the drug binds to the receptor.

“Based on our study, we expect that patients with different genetic variations will react differently to psychedelic-assisted treatments,” said Bryan Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology at UNC and lead author of the study, in a statement. “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.”

The present study did not explore the effects of psychedelics on humans, so further research will be necessary to clarify the exact implications of the research. But as the study authors noted, other institutions are currently conducting clinical trials to determine whether these four psychedelics have therapeutic value, and the findings of the present study “can aid in the design and ultimate interpretation” of these studies.

“In summary, our findings indicate that 5-HT2A receptor SNPs can alter the in vitro pharmacology of some therapeutically promising psychedelics,” the study concluded. “Our results suggest that patients and populations with certain polymorphisms may be differentially amenable to psychedelic-assisted treatments. Taken together, these results may have relevance for the design and interpretation of future clinical trials.”

“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.” 

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